Patent Publication Number: US-2023133924-A1

Title: Optimized expression cassettes for gene therapy

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the benefit of U.S. Provisional Patent Application No. 63/219,651, filed Jul. 8, 2021, which is incorporated herein by reference in its entirety. 
    
    
     FIELD OF THE INVENTION 
     This invention relates generally to gene therapies, e.g., optimized gene expression cassettes, recombinant adeno-associated virus (AAV) virions, and methods for treating and preventing heart disease using the same. 
     REFERENCE TO AN ELECTRONIC SEQUENCE LISTING 
     The contents of the electronic sequence listing (TENA_021_02US_SeqList_ST26.xml; Size: 430,204 bytes; and Date of Creation: Jul. 8, 2022) are herein incorporated by reference in their entirety. 
     BACKGROUND 
     Cardiomyopathy is responsible for about half of cardiac-related deaths. it is estimated that about 1 in 250 to 1 in 10,000 adults are affected by some form of cardiomyopathy (McKenna et al.  Circ Res.  121:722-730 (2017)). Despite major efforts in screening, diagnostics, and therapeutic strategies, the prevalence of cardiomyopathies and incidence of cardiomyopathy-related deaths remains high (Brieler et al.  Am Fam Physician.  96:640-646 (2017)). 
     Cardiomyopathy refers to a collection of conditions of the heart that occur when its ability to pump blood is reduced. Reduction in proper functioning, such as a contractile dysfunction, of the heart muscle can lead to myocardial infarction, heart failure, blood clots, valve problems, and cardiac arrest. Cardiomyopathies can be separated into primary and secondary categories that result in varied phenotypes (McKenna et al.  Circ Res.  121:722-730 (2017)). Primary cardiomyopathies can be genetic, acquired, or mixed in etiology. Genetic cardiomyopathies are inherited and include arrhythmogenic right ventricular dysplasia, hypertrophic, ion channel disorders, left ventricular compaction, and mitochondrial myopathies. Acquired cardiomyopathies are due primarily to non-secondary, non-genetic causes that lead to cardiac complications and include myocarditis, peripartum, tachycardia-induced cardiomyopathy, and stress-induced cardiomyopathy. Cardiomyopathies with mixed etiology are caused by a combination of non-genetic and genetic factors, and include dilated cardiomyopathy and restrictive cardiomyopathy. Secondary cardiomyopathies refer to heart disease resulting from an extra cardiovascular cause. The underlying causes of secondary cardiomyopathies can be endocrine, infection, exposure to toxins, autoimmune related, nutritional, and/or neuromuscular. 
     Cardiomyocytes play a central role cardiomyopathy. Cardiomyocytes, also called cardiac muscle cells, cardiac myocytes, or myocardiocytes, are cardiac cells that make up the heart muscle and are responsible for the contractile function that allows the heart to act as a pump. There are many mechanisms that reduce cardiomyocytes&#39; ability to function properly (Dadson et al.  Clin Sci  ( Lond ) 131:1375-1392 (2017)). In arrhythmogenic right ventricular cardiomyopathy, progressive replacement of cardiomyocytes with fibrotic tissue results in the electrical isolation of cardiomyocytes and atrophy of the ventricular myocardium, the major structure responsible for contractile function in the heart. In mitochondrial cardiomyopathy, a deficiency in ATP production has a direct effect on contractile function in cardiomyocytes that have a high metabolic demand. Cardiomyopathies also emerge as a result of abnormal contractile function resulting from loss of normal Ca 2+  ion-release, uptake, and sequestration processes due to loss of activity in regulatory enzymes, such as sarco/endoplasmic reticulum calcium ATPase (SERCA) (Lennon et al.  Int J Mol Med.  7:131-41 (2001)). 
     Treatment strategies for cardiomyopathy are needed. 
     Gene therapy approaches for the treatment of heart disease often employ vectors configured to transduce cardiac cells and to express a transgene in a cardiac tissue-specific manner. Adeno-associated virus (AAV) vectors, cardiac-specific promoters, or both in combination, may be used to deliver a polynucleotide encoding a gene product (e.g., a therapeutic protein) to heart tissue and thereby express the gene product in that tissue to treat the heart disease. 
     However, achieving high expression of gene products remains challenging, especially in cardiac cells. 
     Given these challenges, there remains a need in the art for improved gene therapy vectors, especially for heart disease. 
     SUMMARY 
     In some aspects, the present invention relates generally to vectors for delivery of a polynucleotide encoding a dwarf open reading frame (DWORF) or another transgene to cardiac cells, e.g, cardiomyocytes. Disclosed herein are recombinant adeno-associated virus virions (rAAV virions), including expression cassettes and capsid proteins, that effectively deliver DWORF polynucleotides into cardiac cells, along with related compositions and methods. In any aspects described herein where DWORF transgene is referenced, DWORF can be substituted by a reference to another transgene expression of which in cardiac cells is desired. In some embodiments, where AAV-based expression vectors and virions are referenced, the disclosure also contemplates use of other viral and non-viral vectors for delivery of transgenes. In particular, any viral and non-viral vectors that can be used for delivery of transgenes into cardiac cells are provided herein. 
     In some aspects, provided herein is an expression cassette comprising a polynucleotide sequence comprising:
     i) one or more promoters, optionally wherein the one or more promoters are cardiac-specific promoters; and   ii) one or more copies of a transgene, optionally wherein the transgene encodes a polypeptide for treating or preventing a heart disease or alleviating symptoms associated with a heart disease; wherein in addition to elements (i) and (ii), the expression cassette comprises one or more of the following:   iii) one or more enhancers, optionally wherein the one or more enhancers are cardiac-specific enhancers;   iv) the one or more copies of a transgene is at least two copies of the transgene;   v) the polynucleotide sequence comprises one or more introns; and/or   vi) at least one copy of the one or more copies of the transgene is codon-optimized.   

     In some embodiments of the expression cassette described above, in addition to elements (i) and (i), the expression cassette comprises one, two, three or all four of elements (iii), (iv), (v) and (vi) (any combination of elements (iii), (iv), (v) and (vi) can be used). In some embodiments of the expression cassette described above, in addition to elements (i) and (ii), the expression cassette comprises one or more enhancers, wherein the one or more enhancers are cardiac-specific enhancers, and/or the polynucleotide sequence comprises one or more introns. In some embodiments of the expression cassette described above, in addition to elements (i) and (ii), the expression cassette comprises one or more enhancers, wherein the one or more enhancers are cardiac-specific enhancers, and the polynucleotide sequence comprises one or more introns. In some embodiments, the one or more introns improve, or can improve, the efficiency of transgene expression. In some embodiments of the expression cassette described above, in addition to elements (i) and (ii), the expression cassette comprises two copies of the transgene, wherein the two copies are not identical, optionally wherein first copy is codon-optimized and second copy is not codon-optimized nucleotide sequence encoding the transgene. In some embodiments of the expression cassette described above, in addition to elements (i) and (ii), the expression cassette comprises two copies of the transgene, wherein the two copies are not identical to each other, optionally wherein first copy is codon-optimized and second copy is not codon-optimized nucleotide sequence encoding the transgene, and further the polynucleotide sequence comprises one or more introns. In some embodiments of the expression cassette described above, in addition to elements (i) and (ii). the expression cassette comprises two copies of the transgene, wherein the two copies are not identical to each other, optionally wherein first copy is codon-optimized and second copy is not codon-optimized nucleotide sequence encoding the transgene, and further the polynucleotide sequence comprises one or more introns, and further the polynucleotide sequence comprises one or more enhancers (e.g., wherein the one or more enhancers are cardiac-specific enhancers). In some embodiments, the one or more introns improve, or can improve, the efficiency of transgene expression. In some embodiments where two copies of the transgene are used, two copies of the promoters are also used. 
     In some embodiments of the expression cassette, the polynucleotide sequence comprises one or more promoters, wherein the one or more promoters are cardiac-specific enhancers. In some embodiments of the expression cassette, at least one promoter is a cardiac-specific promoter, or all of the promoters are cardiac-specific promoters. In some embodiments of the expression cassette, the polynucleotide sequence comprises a single promoter. In some embodiments of the expression cassette, the polynucleotide sequence comprises two promoters. In some embodiments of the expression cassette, at least one promoter of the one or more promoters is a chicken cTnT promoter. In some embodiments, the chicken cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 11. In some embodiments, the chicken cTnT promoter comprises SEQ ID NO: 11. In some embodiments of the expression cassette, at least one promoter of the one or more promoters is a human cTnT promoter. In some embodiments, the human cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 12 or SEQ ID NO: 13. In some embodiments, the human cTnT promoter comprises SEQ ID NO: 12 or SEQ ID NO: 13. In some embodiments, the expression cassette comprises a chicken cTnT promoter and a human cTnT promoter. 
     In some embodiments of the expression cassette, the polynucleotide sequence comprises one or more copies of a transgene, wherein the transgene encodes a polypeptide for treating or preventing a heart disease or alleviating symptoms associated with a heart disease. 
     In some embodiments of the expression cassette, one or more copies of a transgene is at least two copies of the transgene. In some embodiments of the expression cassette, one or more copies of a transgene is two copies of the transgene. In some embodiments, one or more copies of a transgene is at least two copies of the transgene, and wherein the polynucleotide sequence comprises at least two promoters each operably linked to the at least two copies of the transgene. In some embodiments, one or more copies of a transgene is two copies of the transgene, and wherein the polynucleotide sequence comprises two promoters each operably linked to the two copies of the transgene. In some embodiments of the expression cassette comprising two copies of the transgene, the two “copies” are not identical. While not being bound by any theory, using two nucleic acid sequences encoding a polypeptide that are not identical may prevent DNA recombination within the vector. In some embodiments, the expression cassette comprises one copy of the transgene that has the original DNA sequence encoding a polypeptide and one copy of the transgene that has a codon optimized DNA sequence encoding the polypeptide. In some embodiments of the expression cassette comprising two copies of the transgene, the first copy of the transgene is sufficiently different from the second copy of the transgene to prevent DNA recombination. 
     In some embodiments of the expression cassette, the polynucleotide sequence comprises one or more enhancers, optionally wherein the one or more enhancers are cardiac-specific enhancers. In some embodiments of the expression cassette, the polynucleotide sequence comprises two or more enhancers (e.g., 2, 3, or 4 enhancers). In some embodiments of the expression cassette, one or more enhancers are cardiac-specific enhancers (e.g., at least one enhancer is a cardiac-specific enhancer, or 2, 3, or 4, or all of the enhancers are cardiac-specific enhancers). In some embodiments of the expression cassette, the polynucleotide sequence comprises one enhancer. In some embodiments of the expression cassette, the polynucleotide sequence comprises no enhancers. In some embodiments, the one or more cardiac-specific enhancers are selected from a ACTC1 enhancer and αmHC enhancer. In some embodiments, the ACTC1 enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 78. In some embodiments, the ACTC1 enhancer comprises SEQ ID NO: 78. In some embodiments, the αMHC enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 79. In some embodiments, the αMHC enhancer comprises SEQ ID NO: 79. In some embodiments, the expression cassette comprises an αMHC enhancer and an ACTC1 enhancer. In some embodiments of the expression cassette, the enhancer sequence comprises an αMHC enhancer followed by an ACTC1 enhancer. In some embodiments of the expression cassette, the enhancer sequence comprises an ACTC1 enhancer followed by an αMHC enhancer. 
     In some embodiments of the expression cassette, the polynucleotide sequence comprises one or more introns. In some embodiments of the expression cassette, the polynucleotide sequence comprises one intron. In some embodiments of the expression cassette, the polynucleotide sequence comprises two introns. In some embodiments of the expression cassette, the polynucleotide sequence comprises more than two introns. In some embodiments of the expression cassette, one or more introns are the same. In some embodiments of the expression cassette, one or more introns are different from each other. In some embodiments, the expression cassette comprises an intron and the intron is selected from a CMV intron and a chimeric intron. In some embodiments, the CMV intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. In some embodiments, the CMV intron comprises SEQ ID NO: 80. In some embodiments, the chimeric intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81. In some embodiments, the chimeric intron comprises SEQ ID NO: 81. In some embodiments, the expression cassette comprises a CMV intron and a chimeric intron. In some embodiments, the expression cassette does not comprise an intron (e.g., does not comprise a CMV intron or a chimeric intron). 
     In some embodiments of the expression cassette, at least one copy of the one or more copies of the transgene is codon-optimized (e.g., codon-optimized for optimum human expression). In some embodiments of the expression cassette, two copies of the transgene are codon-optimized. In some embodiments of the expression cassette, first copy of the transgene is codon-optimized and second copy of the transgene is not codon optimized (e.g., original DNA sequence) or is otherwise different from the first copy. In some embodiments of the expression cassette, the first copy of the transgene is sufficiently different from the second copy of the transgene to prevent DNA recombination. 
     In some embodiments, the expression cassette further comprises one or more (e.g., two) post-transcriptional regulatory elements (“PTRE”). In some embodiments, the expression cassette further comprises one or more (e.g., two) WPRE sequences. In some embodiments, the expression cassette comprises one WPRE sequence. In some embodiments, the WPRE sequence shares at least 90%, 95%, 96%. 97%, 98%, or 99% identity to SEQ ID NO: 26. In some embodiments, the WPRE sequence comprises SEQ ID NO: 26. In some embodiments, the expression cassette does not comprise a WPRE sequence. 
     In some embodiments, the expression cassette further comprises one or more polyadenylation sequences (“p(A)”), In some embodiments, the expression cassette comprises one polyadenylation sequence. In some embodiments, the expression cassette comprises two polyadenylation sequences. In some embodiments, the polyadenylation sequence is selected from a BGH polyadenylation sequence and a SV40 polyadenylation sequence. In some embodiments, the BGH polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 27. In some embodiments, the BGH polyadenylation sequence comprises SEQ ID NO: 27. In some embodiments, the SV40 polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 28. In some embodiments, the SV40 polyadenylation sequence comprises SEQ ID NO: 28. In some embodiments, the expression cassette comprises a BGH polyadenylation sequence and a SV40 polyadenylation sequence. 
     In some embodiments, the expression cassette comprises 5′ to 3′ arrangement of elements selected from any one of the following:
     (i) 5′-promoter-intron-transgene-PTRE-p(A)-3′;   (ii) 5′-promoter-transgene-PTRE-p(A)-promoter-transgene-PTRE-p(A);   (iii) 5′-enhancer-promoter-transgene-PTRE-p(A)-3′;   (iv) 5′-enhancer-promoter-intron-transgene-PTRE-p(A)-3′;   (v) 5′-enhancer-enhancer-promoter-transgene-PTRE-p(A)-3′;   (vi) 5′-enhancer-enhancer-promoter-intron-transgene-PTRE-p(A)-3′;   (vii) 5′-enhancer-promoter-intron-transgene-PTRE-p(A)-p(A)-transgene-intron-promoter-enhancer-3′;   (viii) 5′-enhancer-promoter-intron-transgene-PTRE-p(A)-enhancer-promoter-intron-transgene-p(A)-3′;   (ix) 5′-p(A)-PTRE-transgene-intron-promoter-enhancer-enhancer-promoter-intron-transgene-p(A)-3′;   (x) 5′-promoter-intron-transgene-PTRE-p(A)-p(A)-transgene-intron-promoter-3′;   (xi) 5′-promoter-intron-transgene-PTRE-p(A)-promoter-intron-transgene-p(A)-3′; and   (xii) 5′-p(A)-PTRE-transgene-intron-promoter-promoter-intron-transgene-p(A)-3′.   

     In some embodiments of the expression cassette, the transgene has an increased expression level compared to an expression cassette comprising a polynucleotide having an arrangement of elements from 5′ to 3′ comprising: 5′-promoter-transgene-WPRE-p(A)-3′. In some embodiments, the increased expression level is between about 1.5-fold and about 150-fold. In some embodiments, the increased expression level is at least 2 fold, at least 5 fold, at least 10 fold, at least 25 fold, at least 50 fold, at least 75 fold, or at least 100 fold. 
     In some embodiments, the expression cassette is flanked by ITRs, In some embodiments, the ITRs share at least 90%, 95%, 96%, 97%, 98%, or 99% identity to one or more of SEQ ID NO: 14 and SEQ ID NO: 15. In some embodiments, the ITRs comprise one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     In some embodiments, the expression cassette comprises from about 1.9 kb to about 3.7 kb. In some embodiments, the expression cassette comprises from about 2.5 kb to about 3.7 kb, optionally from about 2.8 kb to about 3.6 kb. 
     In some embodiments, the transgene in the expression cassette encodes a polypeptide useful in the treatment of a heart disease or disorder, optionally when a wild type copy of the gene is introduced to a subject. In some embodiments, the transgene in the expression cassette encodes a polypeptide which is associated with a heart disease (e.g., where loss of function mutations in the gene encoding the polypeptide are associated with heart disease). 
     In some embodiments, the transgene in the expression cassette encodes a polypeptide selected from: DWORF, JPH2, BAG3, CRYAB, Lamin A isoform of LMNA, Lamin C isoform of LMNA, TNNI3, PLN, LAMP2a, LAMP2b, LAMP2c, DPI isoform of DSP, DPII isoform of DSP, DSG2, and JUP. In some embodiments, the expression cassette comprises a transgene which shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, or SEQ ID NO:229. In some embodiments, the polypeptide shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, or SEQ ID NO:230. 
     In some embodiments, the transgene in the expression cassette encodes a DWORF polypeptide. In some embodiments, the transgene shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:33, SEQ ID NO:44, SEQ ID NO:76, or SEQ ID NO:77. In some embodiments, the polypeptide shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:32, or SEQ ID NO:43. 
     In some embodiments, the expression cassette comprises a 5′ to 3′ arrangement of elements selected from any one of the following:
     (i) 5′-human or chicken TnT promoter-chimeric intron-transgene-WPRE-p(A)-3′;   (ii) 5′-first human or chicken TnT promoter-first copy of transgene-WPRE-p(A)-second human or chicken TnT promoter-second copy of transgene-WPRE-p(A), optionally where the first and second promoter sequences and the first and second copies of the transgene are in the same forward orientation;   (iii) 5′-human TnT promoter-CMV intron-transgene-WPRE-bGHpA-3′;   (iv) 5′-ACTC1e enhancer-cardiac-human TnT promoter-transgene-WPRE-bGHpA-3′;   (v) 5′-αMHCe enhancer-human TnT promoter-transgene-WPRE-bGHpA-3′;   (vi) 5′-ACTC1e enhancer-human TnT promoter-CMV intron-transgene-WPRE-bGHpA-3′;   (vii) 5′-αMHCe enhancer-human TnT promoter-CMV intron-transgene-WPRE-bGHpA-3′;   (viii) 5′-ACTC1e enhancer-αMHCe enhancer-human TnT promoter-transgene-WPRE-bGHpA-3′;   (ix) 5′-αACTC1e enhancer-ACTC1e enhancer-human TnT promoter-transgene-WPRE-bGHpA-3′;   (x) 5′-ACTC1e enhancer-αMHCe enhancer-human TnT promoter-CMV intron-transgene-WPRE-bGHpA-3′;   (xi) 5′-αMHCe enhancer-ACTC1e enhancer-human TnT promoter-CMV intron-transgene-WPRE-bGHpA-3′;   (xii) human TnT promoter-transgene with a codon-optimized polynucleotide sequence-WPRE-bGHpA-3′;   (xiii) 5′-αMHCe enhancer-human TnT promoter-CMV intron-first transgene-WPRE-bGHpA-SV40pA-second transgene (e.g., with a codon-optimized polynucleotide sequence)-chimeric intron-chicken TnT promoter-ACTC1e enhancer-3′, optionally wherein the first transgene and the human TnT promoter are in a forward orientation, and the second transgene and the chicken TnT promoter are in a reverse orientation;   (xiv) 5′-αMHCe enhancer-human TnT promoter-CMV intron-first transgene-WPRE-bGHpA-ACTC1e enhancer-chicken TnT promoter-chimeric intron-second transgene (e.g., with a codon-optimized polynucleotide sequence)-SV40pA-3′, optionally wherein the first transgene, the human TnT promoter, the second transgene and the chicken TnT promoter are in a forward orientation;   (xv) 5′-bGHpA-WPRE-first transgene-CMV intron-human TnT promoter-αMHCe enhancer-ACTC1e enhancer-chicken TnT promoter-chimeric intron-second transgene (e.g., with a codon-optimized polynucleotide sequence)-SV40pA-3′, optionally wherein the first transgene and the human TnT promoter are in a reverse orientation, and the second transgene and the chicken TnT promoter are in a forward orientation;   (xvi) 5′-human TnT promoter-CMV intron-first transgene-WPRE-bGHpA-pSV40pA-second transgene (e.g., with a codon-optimized polynucleotide sequence)-chimeric intron-chicken TnT promoter-3′, optionally wherein the first transgene and the human TnT promoter are in a forward orientation, and the second transgene and the chicken TnT promoter are in a reverse orientation; and   (xvii) 5′-huma TnT promoter-CMV intron-first transgene-WPRE-bGHpA-chicken TnT promoter-chimeric intron-second transgene (e.g., with a codon-optimized polynucleotide sequence)-SV40pA-3′, optionally wherein the first transgene, the human TnT promoter, the second transgene and the chicken TnT promoter are in a forward orientation; and (xix) 5′-bGHpA-WPRE-first transgene-CMV intron-human TnT promoter-chicken TnT promoter-chimeric intron-second transgene (e.g., with a codon-optimized polynucleotide sequence)-SV40pA-3′, optionally wherein the first transgene and the human TnT promoter are in a reverse orientation, and the second transgene and the chicken TnT promoter are in a forward orientation.   

     In some embodiments, the expression cassette comprises 5′ to 3′ arrangement of elements selected from any one of the following:
     (i) 5′-ACTC1e enhancer-αMHCe enhancer-human TnT promoter-CMV intron-transgene-WPRE-bGHpA-3′;   (ii) 5′-αMHCe enhancer-ACTC1e enhancer-human TnT promoter-CMV intron-transgene-WPRE-bGHpA-3′;   (iii) 5′-αMHCe enhancer-human TnT promoter-CMV intron-first transgene-WPRE-bGHpA-SV40pA-second transgene (e.g., with a codon-optimized polynucleotide sequence)-chimeric intron-chicken TnT promoter-ACTC1e enhancer-3′, optionally wherein the first transgene and the human TnT promoter are in a forward orientation, and the second transgene and the chicken TnT promoter are in a reverse orientation;   (iv) 5′-αMHCe enhancer-human TnT promoter-CMV intron-first transgene-WPRE-bGHpA-ACTC1e enhancer-chicken TnT promoter-chimeric intron-second transgene (e.g., with a codon-optimized polynucleotide sequence)-SV40pA-3′, optionally wherein the first transgene, the human TnT promoter, the second transgene and the chicken TnT promoter are in a forward orientation;   (v) 5′-bCHpA-WPRE-first transgene-CMV intron-human TnT promoter-αMHVe enhancer-ACTC1e enhancer-chicken TnT promoter-chimeric intron-second transgene (e.g., with a codon-optimized polynucleotide sequence)-SV40pA-3′, optionally wherein the first transgene and the human TnT promoter are in a reverse orientation, and the second transgene and the chicken TnT promoter are in a forward orientation;   (vi) 5′-human TnT promoter-CMV intron-first transgene-WPRE-bGHpA-pSV40pA-second transgene (e.g., with a codon-optimized polynucleotide sequence)-chimeric intron-chicken TnT promoter-3′, optionally wherein the first transgene and the human TnT promoter are in a forward orientation, and the second transgene and the chicken TnT promoter are in a reverse orientation;   (vii) 5′-huma TnT promoter-CMV intron-first transgene-WPRE-bGHpA-chicken TnT promoter-chimeric intron-second transgene (e.g., with a codon-optimized polynucleotide sequence)-SV40pA-3′, optionally wherein the first transgene, the human TnT promoter, the second transgene and the chicken TnT promoter are in a forward orientation; and   (viii) 5′-WPRE-first transgene-CMV intron-human TnT promoter-chicken TnT promoter-chimeric intron-second transgene (e.g., with a codon-optimized polynucleotide sequence)-SV40pA-3′, optionally wherein the first transgene and the human TnT promoter are in a reverse orientation, and the second transgene and the chicken TnT promoter are in a forward orientation.   

     In some embodiments, the expression cassette is a recombinant expression cassette. 
     In some aspects, provided herein is a recombinant vector comprising any of the expression cassettes described herein. In some embodiments, the vector is a viral vector. In some embodiments, the vector is a non-viral vector. 
     In some aspects, provided herein is a recombinant adeno-associated virus (rAAV) virion, comprising a capsid protein and a viral genome comprising any of the expression cassettes described herein, wherein the expression cassette is flanked by inverted terminal repeats (ITRs). In some embodiments, the ITRs share at least 90%, 95%, 96%, 97%, 98%, or 99% identity to one or more of SEQ ID NO: 14 and SEQ ID NO: 15. In some embodiments, the ITRs share at least 90%, 95%, 96%, 97%, 98%, or 99% identity to one or more of SEQ ID NO: 14 and SEQ ID NO: 15. In some embodiments, the capsid protein shares at least 98%, at least 99%, or 100% identity to an AAV9 capsid protein (SEQ ID NO: 143). In some embodiments, the capsid protein shares at least 98%, at least 99%, or 100% identity to an AAVS capsid protein (SEQ ID NO: 144). In some embodiments, the capsid protein is a chimeric capsid protein. In some embodiments, the capsid protein is an AAV5/AAV9 chimeric capsid protein. In some embodiments, the capsid protein is selected from any one of SEQ ID NOs: 145-200. 
     In some aspects, provided herein is a pharmaceutical composition comprising any of the vectors described herein or any of the rAAV virions described herein, and a pharmaceutically acceptable carrier. 
     In some aspects, provided herein is a kit comprises any of the pharmaceutical compositions described herein, or any components of such pharmaceutical compositions (e.g., a vector or an rAAV virion). 
     In some aspects, provided herein is a method of increasing expression of a polypeptide in a cardiac cell or cardiac tissue comprising contacting a cell with any vector described herein, any rAAV virion described herein, or any pharmaceutical composition described herein. In some embodiments, the cardiac cell is a cardiomyocyte. In some embodiments, the cardiac tissue is heart tissue. In some embodiments, the polypeptide expression is increased between about 1.5-fold and 150-fold. In some embodiments, the polypeptide expression is increased at least 2 fold, at least 5 fold, at least 10 fold, at least 25 fold, at least 50 fold, at least 75 fold, or at least 100 fold. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. 
     In some aspects, provided herein is a method of increasing polypeptide expression in a subject comprising administering to the subject any vector described herein, any rAAV virion described herein, or any pharmaceutical composition described herein. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, following administering, the polypeptide expression is increased in the heart of the subject. In some embodiments, the subject being treated has a heart disease or is at risk of a heart disease. In some embodiments, the subject being treated has borderline or reduced ejection fraction. In some embodiments, the subject being treated has normal ejection fraction. In some embodiments, wherein the subject being treated has a genetic mutation associated with a heart disease (e.g., a mutation in a PLN gene). In some embodiments, the subject has a low or undetectable level of expression of the polypeptide encoded by the transgene, compared to a healthy subject. 
     In some aspects, provided herein is a method of treating or preventing a heart disease or disorder in a subject in need thereof comprising administering to the subject any vector described herein, any rAAV virion described herein, or any pharmaceutical composition described herein. In some embodiments, the subject being treated has a heart disease or disorder. In some embodiments, the subject being treated is a risk of developing a heart disease or disorder. In some embodiments, the heart disease or disorder is cardiomyopathy. In some embodiments, the cardiomyopathy is dilated cardiomyopathy. In some embodiments, the heart disease or disorder is myocardial infarction. In some embodiments, the myocardial infarction is chronic myocardial infarction. In some embodiments, the subject has an inherited risk allele for a heart disease or disorder. In some embodiments, the subject has an inherited risk allele for a heart disease or disorder due to a genetic mutation. In some embodiments, the subject has an inherited risk allele for a heart disease or disorder due to a genetic mutation in a PLN gene (for example, one or more mutations in the PLN gene described herein or known in the art). In some embodiments, the heart disease or disorder is with reduced ejection fraction (HFrEF). In some embodiments, the heart disease of disorder is with preserved ejection fraction (HFpEF). In some embodiments, the method leads to expression of the polypeptide encoded by the transgene in the heart of the subject. In some embodiments, the method leads to expression of the polypeptide encoded by the transgene in cardiomyocytes of the subject. In some embodiments, the method causes no detectable expression of the polypeptide encoded by the transgene in the muscles of the subject except the heart, in the liver of the subject, and/or in the cardiac fibroblasts of the subject. In some embodiments, the method improves one or more measures of cardiac function, optionally fraction shortening and/or left ventricular internal dimension (LVID). In some embodiments, the improvement in cardiac function is observed at or later than week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, and/or week 24, after the administering. In some embodiments, the administering is systemic administration. In some embodiments, the systemic administration is selected from intravenous or intracoronary injection. In some embodiments, when an rAAV virion is administered, it is administered as a unit dose. In some embodiments, the unit dose comprises about 3×10 14  vg/kg or less, about 2×10 14  vg/kg or less, about 1×10 14  vg/kg or less, about 9×10 13  vg/kg or less, about 8×10 13  vg/kg or less, about 7×10 13  vg/kg or less, about 6×10 13  vg/kg or less, about 5×10 13  vg/kg or less, about 4×10 13  vg/kg or less, about 3×10 13  vg/kg or less, about 2×10 13  vg/kg or less, or about 1×10 13  vg/kg or less. In some embodiments, the subject being treated is a mammal. In some embodiments, the subject being treated is a human, 
     In one aspect, the disclosure provides a recombinant adeno-associated virus (rAAV) virion, comprising a capsid protein and a viral genome comprising an expression cassette comprising a polynucleotide sequence encoding a dwarf open reading frame (DWORF) polypeptide operatively linked to a promoter, the expression cassette flanked by inverted terminal repeats. 
     In some embodiments, the DWORF polypeptide shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 1, 3, 4, 7, 9, 23, and 43. In some embodiments, the DWORF polypeptide is selected from SEQ ID NOs: 1, 3, 4, 7, 9, 23, and 43. 
     In some embodiments, the promoter is a chicken cTnT promoter. In some embodiments, the chicken cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 11. In some embodiments, the chicken cTnT promoter comprises SEQ ID NO: 11. In some embodiments, the promoter is a human cTnT promoter. In some embodiments, the human cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 12 or SEQ ID NO: 13. In some embodiments, the human cTnT promoter comprises SEQ ID NO: 12 or SEQ ID NO: 13. 
     In some embodiments, the expression cassette further comprises one or more enhancers. In some embodiments, the enhancer the one or more enhancers are selected from a ACTC1 cardiac enhancer and a αMHC enhancer. In some embodiments, the ACTC1 cardiac enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 78. In some embodiments, the ACTC1 cardiac enhancer comprises SEQ ID NO: 78. In some embodiments, the αMHC enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 79. In some embodiments, the αMHC enhancer comprises SEQ ID NO: 79. 
     In some embodiments, the expression cassette further comprises an intron. In some embodiments, the intron is selected from a CMV intron and a chimeric intron. In some embodiments, the CMV intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. In some embodiments, the CMV intron comprises SEQ ID NO: 80. In some embodiments, the chimeric intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81. In some embodiments, the chimeric intron comprises SEQ ID NO: 81. 
     In some embodiments, the expression cassette further comprises a WPRE sequence. In some embodiments, the WPRE sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 26. In some embodiments, the WPRE sequence comprises SEQ ID NO: 26. 
     In some embodiments, the expression cassette further comprises a polyadenylation sequence. In some embodiments, the polyadenylation sequence is selected from a BGH polyadenylation sequence and a SV40 polyadenylation sequence. In some embodiments, the BGH polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 27. In some embodiments, the BGH polyadenylation sequence comprises SEQ ID NO: 27. In some embodiments, the SV40 polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 28. In some embodiments, the SV40 polyadenylation sequence comprises SEQ ID NO: 28. 
     In some embodiments, the expression cassette is flanked by ITRs. In some embodiments, the ITRs share at least 90%, 95%, 96%, 97%, 98%, or 99% identity to one or more of SEQ ID NO: 14 and SEQ ID NO: 15. In some embodiments, the ITRs comprise one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     In some embodiments, the expression cassette comprises a single promoter. In some embodiments, the expression cassette comprises two promoters. In some embodiments, the expression cassette comprises a single copy a sequence encoding the DWORF polypeptide. In some embodiments, the expression cassette comprises two copies of a sequence encoding the DWORF polypeptide. In some embodiments, where the expression cassette comprises two copies of a sequence encoding the DWORF polypeptide, the two “copies” are not identical. While not being bound by any theory, using two nucleic acid sequences encoding a polypeptide that are not identical may prevent DNA recombination within the vector. In some embodiments, the expression cassette comprises one copy that has the original DNA sequence encoding the DWORF polypeptide and one copy that has a codon optimized DNA sequence encoding the DWORF polypeptide. In some embodiments, the expression cassette comprises two copies of a sequence encoding the DWORF polypeptide, wherein one copy is codon-optimized and one copy is not codon optimized. In some embodiments, the expression cassette comprises one, two, three, or four enhancers. In some embodiments, the expression cassette comprises one or two introns. In some embodiments, the expression cassette comprises one or two WPRE sequences. In some embodiments, the expression cassette comprises one or two polyadenylation sequences. 
     In some embodiments, the expression cassette comprises about 3.2 kb, about, about 3.3 kb, about 3.4 kb, about 3.5 kb, about 3.6 kb, about 3.7 kb, or less. In some embodiments, the expression cassette comprises about 1.9 kb, about 2.1 kb, about 2.2 kb, about 2.3 kb, about 2.4 kb, about 2.5 kb, about 2.6 kb, about 2.7 kb, about 2.8 kb, about 2.9 kb, about 3.0 kb, about 3.1 kb, about 3.2 kb, or more. 
     In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75. In some embodiments, wherein the expression cassette comprises any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 61. In some embodiments, the expression cassette comprises SEQ ID NO: 61. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 62. In some embodiments, the expression cassette comprises SEQ ID NO: 62. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 63. In some embodiments, the expression cassette comprises SEQ ID NO: 63. 
     In some embodiments, the capsid protein shares at least 98%, at least 99%, or 100% identity to an AAV9 capsid protein (SEQ ID NO: 143). In some embodiments, the capsid protein shares at least 98%, at least 99%, or 100% identity to an AAV5 capsid protein (SEQ ID NO: 144). In some embodiments, the capsid protein is a chimeric capsid protein. In some embodiments, the capsid protein is an AAV5/AAV9 chimeric capsid protein. In some embodiments, the capsid protein is selected from any one of SEQ ID NOs: 145-200. 
     In one aspect, the disclosure provides an expression cassette comprising polynucleotide sequence encoding a dwarf open reading frame (DWORF) polypeptide operatively linked to a promoter. In some embodiments, the DWORF polypeptide shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NOs: 1, 3, 4, 7, 9, 23, and 43. In some embodiments, the DWORF polypeptide is selected from SEQ ID NOs: 1, 3, 4, 7, 9, 23, and 43. 
     In some embodiments, the promoter is a chicken cTnT promoter. In some embodiments, the chicken cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ NO: 11. In some embodiments, the chicken cTnT promoter comprises SEQ ID NO: 11. In some embodiments, the promoter is a human cTnT promoter. In some embodiments, the human cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 12 or SEQ ID NO: 13. In some embodiments, the human cTnT promoter comprises SEQ ID NO: 12 or SEQ ID NO: 13. 
     In some embodiments, the expression cassette further comprises one or more enhancers. In some embodiments, the enhancer the one or more enhancers are selected from a ACTC1 cardiac enhancer and a αMHC enhancer. In some embodiments, the ACTC1 cardiac enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 78. In some embodiments, the ACTC1 cardiac enhancer comprises SEQ ID NO: 78. In some embodiments, the αMHC enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 79. In some embodiments, the αMHC enhancer comprises SEQ ID NO: 79. 
     In some embodiments, the expression cassette further comprises an intron. In some embodiments, the intron is selected from a CMV intron and a chimeric intron. In some embodiments, the CMV intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. In some embodiments, the CMV intron comprises SEQ ID NO: 80. In some embodiments, the chimeric intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81. In some embodiments, the chimeric intron comprises SEQ ID NO: 81. 
     In some embodiments, the expression cassette further comprises a WPRE sequence. In some embodiments, the WPRE sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 26. In some embodiments, the WPRE sequence comprises SEQ ID NO: 26. 
     In some embodiments, the expression cassette further comprises a polyadenylation sequence. In some embodiments, the polyadenylation sequence is selected from a BGH polyadenylation sequence and a SV40 polyadenylation sequence. In some embodiments, the BGH polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 27. In some embodiments, the BGH polyadenylation sequence comprises SEQ ID NO: 27. In some embodiments, the SV40 polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 28. In some embodiments, the SV40 polyadenylation sequence comprises SEQ ID NO: 28. 
     In some embodiments, the expression cassette is flanked by ITRs. In some embodiments, the ITRs share at least 90%, 95%, 96%, 97%, 98%, or 99% identity to one or more of SEQ ID NO: 14 and SEQ ID NO: 15. In some embodiments, the ITRs comprise one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     In some embodiments, the expression cassette comprises a single promoter. In some embodiments, the expression cassette comprises two promoters. In some embodiments, the expression cassette comprises a single copy a sequence encoding the DWORF polypeptide. In some embodiments, the expression cassette comprises two copies of a sequence encoding the DWORF polypeptide. In some embodiments, the expression cassette comprises one, two, three, or four enhancers. In some embodiments, the expression cassette comprises one or two introns. In some embodiments, the expression cassette comprises one or two WPRE sequences. In some embodiments, the expression cassette comprises one or two polyadenylation sequences. 
     In some embodiments, the expression cassette comprises about 3.2 kb, about, about 3.3 kb, about 3.4 kb, about 3.5 kb, about 3.6 kb, about 3.7 kb, or less. In some embodiments, the expression cassette comprises about 1.9 kb, about 2.1 kb, about 2.2 kb, about 2.3 kb, about 2.4 kb, about 2.5 kb, about 2.6 kb, about 2.7 kb, about 2.8 kb, about 2.9 kb, about 3.0 kb, about 3.1 kb, about 3.2 kb, or more. 
     In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75. In some embodiments, the expression cassette comprises any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 61. In some embodiments, the expression cassette comprises SEQ ID NO: 61. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 62. In some embodiments, the expression cassette comprises SEQ ID NO: 62. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 63. In some embodiments, the expression cassette comprises SEQ ID NO: 63. 
     In some embodiments, the expression cassette comprises a 5′ inverted terminal repeat and a 3′ inverted terminal repeat. 
     In one aspect, the disclosure provides a pharmaceutical composition comprising the rAAV virion disclosed herein and an pharmaceutically acceptable diluent. In another aspect, the disclosure provides a kit comprising a pharmaceutical composition provided herein. 
     In one aspect, the disclosure provides a method of increasing DWORF expression in a cell comprising contacting a cell with the rAAV virion disclosed herein or the pharmaceutical composition disclosed herein. In some embodiments, the cell is a cardiac cell. In some embodiments, the cardiac cell is a cardiomyocyte. In some embodiments, DWORF expression is increased between about 1.5-fold and 150-fold. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. 
     In one aspect, the disclosure provides a method of increasing DWORF expression in a tissue comprising contacting the tissue with the rAAV virion disclosed herein or the pharmaceutical composition disclosed herein. In some embodiments, the tissue is cardiac tissue. In some embodiments, DWORF expression is increased between about 1.5-fold and 150-fold. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. 
     In one aspect, the disclosure provides a method of increasing DWORF expression in an organ comprising contacting the organ with the rAAV virion disclosed herein or the pharmaceutical composition disclosed herein. In some embodiments, DWORF expression is increased between about 1.5-fold and 150-fold. 
     In some embodiments, the organ is a heart. In some embodiments, the heart is diseased or is at risk of heart disease. In some embodiments, the heart has reduced or borderline ejection fraction. In some embodiments, the heart has a normal ejection fraction. 
     In some embodiments, the heart comprises a genetic mutation associated with a heart disease. In some embodiments, the genetic mutation is a PLN mutation. In some embodiments, the heart has low or undetectable DWORF expression compared to a healthy heart. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. 
     In one aspect, the disclosure provides a method of increasing DWORF expression in a subject comprising administering to the subject the rAAV virion disclosed herein or the pharmaceutical composition disclosed herein. In some embodiments, the subject is an animal. In some embodiments, the subject is a human. In some embodiments, DWORF expression is increased in the heart of the subject. In some embodiments, the subject has a heart disease or is at risk of a heart disease. In some embodiments, the subject has borderline or reduced ejection fraction. In some embodiments, the subject has normal ejection fraction. In some embodiments, the subject has a genetic mutation associated with a heart disease. In some embodiments, the genetic mutation is a PLN mutation. In some embodiments, the subject has a low or undetectable level of DWORF expression compared to a healthy subject. 
     In one aspect, the disclosure provides a method of treating a heart disease or disorder in a subject in need thereof comprising administering to the subject the rAAV virion disclosed herein or the pharmaceutical composition disclosed herein. 
     In some embodiments, the subject has a heart disease or disorder. In some embodiments, the subject is a risk of developing a heart disease or disorder. In some embodiments, the heart disease or disorder is cardiomyopathy. In some embodiments, the heart disease or disorder is dilated cardiomyopathy. In some embodiments, the heart disease or disorder is myocardial infarction. In some embodiments, the heart disease or disorder is chronic myocardial infarction. In some embodiments, the heart disease or disorder is acute myocardial infarction. 
     In some embodiments, the subject has an inherited risk allele for a heart disease or disorder. In some embodiments, the inherited risk allele comprises a mutation to the PLN gene. In some embodiments, the mutation to the PLN gene is a PLN promoter mutation. In some embodiments, the mutation to the PLN gene is a PLNL39stop mutation. In some embodiments, the mutation to the PLN gene is a RC9 mutation. In some embodiments, the mutation to the PLN gene is a R9L mutation. In some embodiments, the mutation to the PLN gene is a PLN gene duplication. In some embodiments, the mutation to the PLN gene is a R14del mutation. 
     In some embodiments, the heart disease or disorder is with reduced ejection fraction (HFrEF). In some embodiments, the heart disease of disorder is with preserved ejection fraction (HFpEF). 
     In some embodiments, the method causes expression of the DWORF polypeptide in the heart of the subject. In some embodiments, the method causes expression of the DWORF polypeptide in cardiomyocytes. 
     In some embodiments, the method causes no detectable expression of the DWORF polypeptide in the muscles of the subject except the heart. In some embodiments, the method causes no detectable expression of the DWORF polypeptide in the liver of the subject. In some embodiments, the method causes no detectable expression of the DWORF polypeptide in cardiac fibroblasts. 
     In some embodiments, the method improves one or more measures of cardiac function, optionally fraction shortening and/or left ventricular internal dimension (LVID). In some embodiments, the improvement in cardiac function is observed at weeks 2 through week 16. In some embodiments, the method reduces cardiac remodeling. In some embodiments, the method counteracts a decrease in DWORF expression in subjects suffering from or at risk of a heart disease. 
     In some embodiments, the rAAV virion is administered by systemic administration. In some embodiments, the systemic administration is selected from intravenous or intracoronary injection. 
     In some embodiments, the rAAV is administered as a unit dose. In some embodiments, the unit dose comprises about 3×10 14  vg/kg or less, about 2×10 14  vg/kg or less, about 1×10 14  vg/kg or less, about 9×10 13  vg/kg or less, about 8×10 13  vg/kg or less, about 7×10 13  vg/kg or less, about 6×10 13  vg/kg or less, about 5×10 13  vg/kg or less, about 4×10 13  vg/kg or less, about 3×10 13  vg/kg or less, about 2×10 13  vg/kg or less, or about 1×10 13  vg/kg or less. 
     In one aspect, the disclosure provides a method of alleviating one or more symptoms of a heart disease or disorder in a subject in need thereof comprising administering the rAAV virion disclosed herein or the pharmaceutical composition disclosed herein. 
     In one aspect, the disclosure provides a method of improving one or more symptoms of a heart disease or disorder in a subject in need thereof comprising administering the rAAV virion disclosed herein or the pharmaceutical composition disclosed herein. 
     In one aspect, the disclosure provides a method of preventing one or more symptoms of a heart disease or disorder in a subject in need thereof comprising administering the rAAV virion disclosed herein or the pharmaceutical composition disclosed herein. 
     In one aspect, the disclosure provides an expression cassette comprising a polynucleotide comprising a 5′ to 3′ arrangement of elements, wherein the elements comprise: i) one or more promoters; ii) optionally one or more enhancers; iii) optionally one or more introns; iv) one or more transgenes; v) optionally one or more WPRE sequences; and vi) optionally one or more polyadenylation sequences, p(A). In some embodiments, the 5′ to 3′ arrangement of elements is selected from: i) 5′-promoter-intron-transgene-WPRE-p(A)-3′; ii) 5′-enhancer-promoter-transgene-WPRE-p(A)-3′; iii) 5′-enhancer-enhancer-promoter-transgene-WPRE-p(A)-3′; iv) 5′-enhancer-enhancer-promoter-intron-transgene-WPRE-p(A)-3′; v) 5′-enhancer-enhancer-promoter-intron-transgene-WPRE-p(A)-3′; vi) 5′-enhancer-promoter-intron-transgene-WPRE-p(A)-p(A)-transgene-intron-promoter-enhancer-3′; vii) 5′-enhancer-promoter-intron-transgene-WPRE-p(A)-enhancer-promoter-intron-transgene-p(A)-3′; viii) 5′-p(A)-WPRE-transgene-intron-promoter-enhancer-enhancer-promoter-intron-transgene-p(A)-3′; ix) 5′-promoter-intron-transgene-WPRE-p(A)-p(A)-transgene-intron-promoter-3′; x) 5′-promoter-intron-transgene-WPRE-p(A)-promoter-intron-transgene-p(A)-3′; and xi) 5′-p(A)-WPRE-transgene-intron-promoter-promoter-intron-transgene-p(A)-3′. In some embodiments, the transgene has an increased expression level compared to a second expression cassette comprising a polynucleotide having an arrangement of elements from 5′ to 3′ comprising: 5′-promoter-transgene-WPRE-p(A)-3′. In some embodiments, the increased expression level is between about 1.5-fold and about 150-fold compared to the second expression cassette. 
     In one aspect, the disclosure provides a recombinant adeno-associated virus (rAAV) virion, comprising a capsid protein and a viral genome comprising an expression cassette of any one of disclosed herein, the expression cassette flanked by inverted terminal repeats. In some embodiments, the expression cassette comprises a transgene, wherein the transgene encodes a polypeptide use for treating or a preventing a heart disease, or alleviating symptoms associated with a heart disease. In some embodiments, the capsid protein is selected from any one of SEQ ID NOs: 145-200. 
    
    
     
       BRIEF DESCRIPTIONS OF DRAWINGS 
         FIG.  1    shows a diagram of illustrative embodiments of expression cassettes comprising a polynucleotide encoding a promoter, a DWORF polypeptide, a WPRE sequence, and a poly(A) signal sequence flanked by AAV inverted terminal repeats. 
         FIG.  2    is a graph showing expression of GFP delivered to human induced pluripotent stem cell derived cardiomyocytes in vitro using an embodiment of an expression cassette packaged into an rAAV virion. 
         FIG.  3    is a graph showing expression of human DWORF polypeptide delivered in vivo in a murine model using an embodiment of an expression cassette packed into an rAAV virion using an AAV9 capsid protein. 
         FIG.  4 A  is a graph showing expression of human DWORF in induced pluripotent stem cell derived cardiomyocytes using an embodiment of an expression cassette packaged into an rAAV virion one of several AAV protein capsid proteins described herein. 
         FIG.  4 B  is a series of images showing expression of GFP using an embodiment of an expression cassette described herein packaged into an rAAV virion one of several AAV protein capsid proteins described herein. 
         FIG.  5 A  is a graph showing DWORF RNA expression in heart tissue from animals treated with rAAV virions containing an embodiment of an expression cassette packaged with one of five chimeric capsid proteins or the AAV9 capsid protein. 
         FIG.  5 B  is an immunoblot showing DWORF protein levels in heart tissue from animals treated with rAAV virions containing an embodiment of an expression cassette packaged with one of four chimeric capsid proteins or the AAV9 capsid protein. 
         FIG.  6 A  is a graph showing improved ejection fraction in a PLN-R14 Δ/Δ  mouse model following treatment with an embodiment of an expression cassette packaged into an rAAV virion using AAV9 protein capsid. 
         FIG.  6 B  is a graph showing improved fractional shortening in a PLN-R14 Δ/Δ  mouse model following treatment with an embodiment of an expression cassette packaged into an rAAV virion using AAV9 protein capsid. 
         FIG.  7 A  shows a diagram of an illustrative expression cassette orientation comprising a polynucleotide encoding a promoter, a DWORF polypeptide, a WPRE sequence, and a poly(A) signal sequence flanked by AAV inverted terminal repeats. 
         FIG.  7 B  shows a diagram of illustrative expression cassette orientations comprising a polynucleotide encoding a promoter, one or more enhancers, an intron, a DWORF polypeptide, a WPRE sequence, and a poly(A) signal sequence flanked by AAV inverted terminal repeats. 
         FIG.  7 C  shows a diagram of illustrative expression cassette orientations comprising a polynucleotide encoding a promoter, one or more enhancers, an intron, a DWORF polypeptide, a WPRE sequence, and a poly(A) signal sequence flanked by AAV inverted terminal repeats. 
         FIG.  8 A  is a schematic diagram which outlines the strategy for assessing the expression of DWORF in cardiomyocytes mice retro-orbitally injected with AAV9:DWORF constructs containing various regulatory elements and arrangements in vivo. 
         FIG.  8 B  is a western blot which demonstrates the expression of DWORF and GAPDH in cardiomyocytes mice retro-orbitally injected with AAV9:DWORF constructs containing various regulatory elements and arrangements in vivo. 
         FIG.  8 C  is a chart showing the DWORF expression level in an animal model achieved using a panel of rAAV virions comprising expression cassettes encoding a DWORF polypeptide. 
         FIG.  9    is a plot showing improved ejection fraction in an animal model of cardiomyopathy treated with a panel of rAAV virions comprising expression cassettes encoding a DWORF polypeptide. 
         FIG.  10    is a plot showing preserved ejection fraction in an animal model of cardiomyopathy treated with a panel of rAAV virions comprising expression cassettes encoding a DWORF polypeptide. 
         FIG.  11 A  is a schematic diagram of DWORF gene therapy efficacy study in the MLP-KO DCM mouse model. 
         FIGS.  11 B and  11 C  demonstrate that AAV9:DWORF constructs containing novel promoters improve the ejection fraction relative to a saline control in the MLP-KO DCM mouse model. 
         FIGS.  11 D and  11 E  demonstrate that AAV9:DWORF constructs improved exercise capacity, including running distance and time to exhaustion, in the MLP-KO DCM mouse model 26 weeks post-treatment. 
         FIG.  12 A  is a schematic diagram of detailing DWORF gene therapy tolerability study in naïve mice. 
         FIG.  12 B  demonstrates that AAV9:pHZ21 is well tolerated in naïve mice up to 2×10 14  vg/kg dose with no difference in body weight, ejection fraction, heart rate, and left ventricular mass (LV mass). 
     
    
    
     DETAILED DESCRIPTION 
     In some aspects, described herein are optimized gene therapy expression cassettes, and their use in the treatment of heart disease. In some aspects, described herein are gene therapy expression cassettes that are able to mediate high expression of transgenes. In some embodiments, described herein are cardiac-specific gene therapy expression cassettes that are able to mediate significantly higher expression of a transgene than can be achieved using a cTnT promoter alone (e.g., a chicken cTnT promoter alone and/or a human cTnT promoter alone) or using the expression cassette depicted in  FIG.  7 A . In some aspects, described herein are gene therapy expression cassettes that allow to lower the viral load while achieving desired expression of a transgene. In some aspects, described herein are gene therapy expression cassettes that allow to achieve durable expression of a transgene. In some embodiments, described herein are gene therapy expression cassettes that allow to achieve expression of a transgene for at least, or more than, 12 weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, 24 weeks, or 26 weeks, after administration of a gene therapy expression cassette comprising the transgene to a subject. In some embodiments, described herein are gene therapy expression cassettes that allow to achieve expression of a transgene for at least, or more than, 24 weeks or at least 6 months after administration of a gene therapy expression cassette comprising the transgene to a subject. In some aspects, administration of a gene therapy expression cassette described herein to a subject results in one or more improvements in cardiac function (e.g., an improvement in ejection fraction or an improvement in exercise capacity). In some embodiments, administration of a gene therapy expression cassette described herein to a subject results in a durable improvement in cardiac function (e.g., a durable improvement in ejection fraction or a durable improvement in exercise capacity). In some embodiments, administration of a gene therapy expression cassette described herein to a subject results in one or more improvements in cardiac function for at least, or more than, 12 weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, 24 weeks, or 26 weeks after the administration. In some embodiments, administration of a gene therapy expression cassette described herein to a subject results in one or more improvements in cardiac function for at least, or more than, 24 weeks or at least 6 months after the administration. In some embodiments, a gene therapy expression cassette described herein allows for cardiac cell-specific expression of a transgene (e.g., cardiomyocyte-specific expression of a transgene). 
     In some aspects, the present disclosure provides a viral or a non-viral vector comprising an expression cassette encoding a gene product, and methods of use thereof. In some embodiments, the expression cassettes described herein comprise a polynucleotide encoding a gene product operably linked to a cardiac cell-specific promoter and/or enhancer (such as any combination of cardiac cell-specific promoters and enhancers described herein, in any orientation as described herein). In some embodiments, the expression cassettes described herein comprise two copies of a polynucleotide encoding a gene product and a cardiac cell-specific promoter (such as any combination of such sequences, in any orientation as described herein). In some embodiments, the expression cassettes described herein comprise a poly nucleotide encoding a gene product operably linked to a cardiac cell-specific promoter and/or enhancer (such as one promoter, or any combination of cardiac cell-specific promoters and enhancers described herein, in any orientation as described herein), a WPRE sequence, and/or one or two copies of a polyA sequence (such as any combination of such sequences, in any orientation as described herein). In some embodiments, the expression cassettes described herein comprise a polynucleotide encoding a gene product operably linked to a cardiac cell-specific promoter and/or an intron. In some embodiments, the expression cassettes described herein comprise one or two copies of a polynucleotide encoding a gene product, one or two copies of a cardiac cell-specific promoter, one, two or more copies of a cardiac-specific enhancer, and/or one or more intron sequences (such as any combination of such sequences, in any orientation as described herein). In some embodiments, the expression cassettes described herein comprise one or two copies of a polynucleotide encoding a gene product, one or two copies of a cardiac cell-specific promoter, one, two or more copies of a cardiac-specific enhancer, one or more intron sequences (such as any combination of such sequences, in any orientation as described herein). a WPRE sequence, and one or two copies of a polyA sequence (such as any combination of such sequences, in any orientation as described herein). In some embodiments, the vectors comprising the expression cassettes described herein may, for example, transduce cardiac cells. In some embodiments, targeted cardiac cells express the gene product, e.g., provide a high level of expression of the gene product. In some aspects, the present disclosure provides pharmaceutical compositions comprising the vectors described herein. In some aspects, the disclosure provides methods for treating a subject diagnosed with or at risk of a heart disease (e.g., cardiomyopathy) using the vectors and pharmaceutical compositions of the disclosure. 
     In some aspects, the present disclosure provides recombinant adeno-associated virus (rAAV) virions as a vector for the expression cassette described herein. 
     Abnormal calcium handling is a universal characteristic of cardiomyopathy, and reduced sarco/endoplasmic reticulum calcium ATPase (SERCA) activity plays a central role in both the initiation and progression of the disease. SERCA is a calcium pump that promotes the uptake, maintenance, and cycling of Ca 2+  ions in cardiac cells, such as cardiomyocytes. SERCA activity is regulated by an inhibitory peptide, phospholamban. There is significant interest in increasing the activity of SERCA by increasing the abundance of a polypeptide called Dwarf Open Reading Frame (DWORF) that enhances SERCA activity through its direct displacement of the SERCA inhibitory peptide phospholamban. Contacting SERCA with DWORF is a strategy for increasing SERCA activity in a cell. 
     In some aspects, the present disclosure provides recombinant adeno-associated virus (rAAV) virions comprising a polynucleotide encoding a DWORF polypeptide, or a functional variant thereof, and methods of use thereof. In some embodiments, the rAAV virions described herein comprise a polynucleotide encoding a DWORF polypeptide, or a functional variant thereof, operably linked to a cardiac cell-specific promoter and/or enhancer (such as any combination of cardiac cell-specific promoters and enhancers described herein, in any orientation as described herein). In some embodiments, the rAAV virions described herein comprise one or two copies of a polynucleotide encoding a DWORF polypeptide, or a functional variant thereof, a WPRE sequence, and one or two copies of a polyA sequence (such as any combination of such sequences, in any orientation as described herein). In some embodiments, the rAAV virions described herein comprise a polynucleotide encoding a DWORF polypeptide operably linked to a cardiac cell-specific promoter and/or an intron. In some embodiments, the rAAV virions described herein comprise one or two copies of a polynucleotide encoding DWORF, one or two copies of a cardiac cell-specific promoter, one, two or more copies of a cardiac-specific enhancer, and/or one or more intron sequences (such as any combination of such sequences, in any orientation as described herein). In some embodiments, the rAAV virions described herein comprise one or two copies of a polynucleotide encoding DWORF, one or two copies of a cardiac cell-specific promoter, one, two or more copies of a cardiac-specific enhancer, one or more intron sequences (such as any combination of such sequences, in any orientation as described herein). a WPRE sequence, and one or two copies of a poly A sequence (such as any combination of such sequences, in any orientation as described herein). In some embodiments, the rAAV virions described herein may, for example, transduce cardiac cells with a polynucleotide with a sequence encoding DWORF polypeptide operatively linked to a cardiac cell-specific promoter region into the host cell genome. In some embodiments, targeted cardiac cells express the DWORF polypeptide and may have increased SERCA activity. Also provided in the disclosure are pharmaceutical compositions comprising the rAAV virions described herein. In an aspect, the disclosure provides methods for treating a subject diagnosed with or at risk of cardiomyopathy using the rAAV virions and pharmaceutical compositions of the disclosure. 
     Terminology 
     Unless the context indicates otherwise, the features of the invention can be used in any combination. Any feature or combination of features set forth can be excluded or omitted. Certain features of the invention, which are described in separate embodiments may also be provided in combination in a single embodiment. Features of the invention, which are described in a single embodiment may also be provided separately or in any suitable sub-combination. 
     Generally, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The detailed description is divided into sections only for the reader&#39;s convenience and disclosure found in any section may be combined with that in another section. 
     The practice of the present disclosure will employ, unless otherwise indicated, conventional techniques of tissue culture, immunology, molecular biology, cell biology and recombinant DNA, which are within the skill of the art. See, e.g., Sambrook and Russell eds. (2001) Molecular Cloning: A Laboratory Manual, 3 rd  edition; Ausubel et al. eds. (2007) Current Protocols in Molecular Biology; Methods in Enzymology (Academic Press, Inc., N.Y.); MacPherson et al. (1991) PCR 1:A Practical Approach (IRL Press at Oxford University Press); MacPherson et al. (1995) PCR 2: A Practical Approach; Harlow and Lane eds. (1999) Antibodies, A Laboratory Manual; Freshney (2005) Culture of Animal Cells: A Manual of Basic Technique, 5 th  edition; Gait ed. (1984) Oligonucleotide Synthesis; U.S. Pat. No. 4,683,195; Hames and Higgins eds. (1984) Nucleic Acid Hybridization; Anderson (1999) Nucleic Acid Hybridization; Hames and Higgins eds. (1984) Transcription and Translation; IRL Press (1986) Immobilized Cells and Enzymes; Perbal (1984) A Practical Guide to Molecular Cloning; Miller and Calos eds. (1987) Gene Transfer Vectors for Mammalian Cells (Cold Spring Harbor Laboratory); Makrides ed. (2003) Gene Transfer and Expression in Mammalian Cells; Mayer and Walker eds. (1987) Immunochemical Methods in Cell and Molecular Biology (Academic Press. London); Herzenberg et al. eds (1996) Weir&#39;s Handbook of Experimental Immunology; Manipulating the Mouse Embryo: A Laboratory Manual, 3 rd  edition (2002) Cold Spring Harbor Laboratory Press; Sohail (2004) Gene Silencing by RNA Interference: Technology and Application (CRC Press); and Sell (2013) Stem Cells Handbook. 
     The conjunction “and/or” means both “and” and “or,” and lists joined by “and/or” encompasses all possible combinations of one or more of the listed items. 
     As used herein, the term “about,” when used to modify a numeric value, indicates that deviations of up to 10% above and below the mimetic value remain within the intended meaning of the recited value. 
     “AAV” is an abbreviation for adeno-associated virus. The term covers all subtypes of AAV, except where a subtype is indicated, and to both naturally occurring and recombinant forms. The abbreviation “rAAV” refers to recombinant adeno-associated virus. “AAV” includes AAV or any subtype. “AAV5” refers to AAV subtype 5. “AAV9” refers to AAV subtype 9. The genomic sequences of various serotypes of AAV, as well as the sequences of the native inverted terminal repeats (ITRs), Rep proteins, and capsid subunits may be found in the literature or in public databases such as GenBank. See, e.g., GenBank Accession Numbers NC_002077 (AAV1), AF063497 (AAV1), NC_001401 (AAV2), AF043303 (AAV2), NC_001729 (AAV3), NC_001829 (AAV4), U89790 (AAV4), NC_006152 (AAV5), AF513851 (AAV7), AF513852 (AAV8), NC_006261 (AAV8), and AY530579 (AAV9). Publications describing AAV include Srivistava et al. (1983)  J. Virol.  45:555; Chiorini et al. (1998)  J. Virol.  71:6823; Chiorini et al. (1999)  J. Virol.  73:1309; Bantel-Schaal et al. (1999)  J. Virol.  73:939; Xiao et al. (1999)  J. Virol.  73:3994; Muramatsu et al. (1996)  Virol.  221:208; Shade of al. (1986)  J. Virol.  58:921; Gao et al. (2002)  Proc. Nat. Acad. Sci. USA  99: 11854; Moris et al. (2004)  Virology  33:375-383; Int&#39;l Pat. Publ Nos, WO2018/222503A1, WO2012/145601A2, WO2000/028061A2, WO1999/61601A2, and WO1998/11244A2; U.S. patent application Ser. Nos. 15/782,980 and 15/433,322; and U.S. Pat. Nos. 10,036,016, 9,790,472, 9,737,618, 9,434,928, 9,233,131, 8,906,675, 7,790,449, 7,906,111, 7,718,424, 7,259,151, 7,198,951, 7,105,345, 6,962,815, 6,984,517, and 6,156,303. 
     An “rAAV virion” refers to a viral particle including at least one viral capsid protein (e.g. VP1) and an encapsidated rAAV vector (or fragment thereof). 
     An “infectious” virion or viral particle is one that comprises a competently assembled viral capsid and is capable of delivering a polynucleotide component into a cell for which the virion is tropic. 
     “Packaging” refers to a series of intracellular events that result in the assembly of an rAAV virion including encapsidation of the rAAV vector. AAV “rep” and “cap” genes refer to polynucleotide sequences encoding replication and encapsidation proteins of adeno-associated virus. AAV rep and cap are referred to herein as AAV “packaging genes.” Packaging requires either a helper virus itself or, more commonly in recombinant systems, helper virus function supplied by a helper-free system (i.e. one or more helper plasmids). A “helper virus” for AAV refers to a virus that allows AAV (e,g. wild-type AAV) to be replicated and packaged by a mammalian cell. The helper viruses may be an adenovirus, herpesvirus or poxvirus, such as vaccinia. 
     The term “inverted terminal repeats” or “ITRs” as used herein refers to AAV viral cis-elements named so because of their symmetry. These elements are essential for efficient multiplication of an AAV genome. In some embodiments, the minimal elements indispensable for ITR function are a Rep-binding site and a terminal resolution site plus a variable palindromic sequence allowing for hairpin formation. 
     The terms “parental capsid” or “parental sequence” refer to a reference sequence from which a particle capsid or sequence is derived. Unless otherwise specified, parental sequence refers to the sequence of the wild-type capsid protein of the same serotype as the engineered capsid protein. 
     “Recombinant,” as applied to a polynucleotide means that the polynucleotide is distinct from a polynucleotide found in nature (e.g., the polynucleotide is the product of various combinations of cloning, restriction or ligation steps, and other procedures, or the polynucleotide is assembled from synthetic oligonucleotides. A “recombinant” protein is a protein produced from a recombinant polypeptide. A recombinant virion is a virion that comprises a recombinant polynucleotide and/or a recombinant protein, e.g. a recombinant capsid protein. 
     As used herein, the term “percent sequence identity,” and the term “identity” when it is used to refer to % sequence identity, with respect to a reference nucleic acid or amino acid sequence is the percentage of nucleic acid bases or amino acid residues in a candidate sequence that are identical with the nucleic acid bases or amino acid residues in the reference sequence, respectively, after aligning the sequences and introducing gaps, if necessaty, to achieve the maximum percent sequence identity. Methods of sequence alignment are well known in the art. Sequences can be aligned using various computer programs, such BLAST, available at ncbi.nlm.nih.gov. Alignments can be made using publicly available computer software such as BLASTp, BLASTn, BLAST-2, ALIGN or MegAlign Pro (DNASTAR) software. Other techniques for alignment are described in Methods in Enzymology, vol. 266: Computer Methods for Macromolecular Sequence Analysis (1996); and Meth. Mol. Biol. 70: 173-187 (1997);  J. Mol. Biol.  48: 44. Skill artisans are capable of choosing an appropriate alignment method depending on various factors including sequence length, divergence, and the presence of absence of insertions or deletions with respect to the reference sequence. 
     The terms “operably linked” and “operatively linked” refer to a nucleic acid sequence placed into a functional relationship with another nucleic acid sequence. These terms, as used herein, have a meaning commonly known in the art. For example, a promoter is operably linked to a gene when that promoter is placed in a location that permits that promoter to initiate transcription of that gene. An enhancer is operably linked to a gene when that enhancer, when bound by an appropriate transcription factor, can regulate (e.g., enhance) expression of that gene. 
     “Treatment,” “treating,” and “treat” are defined as acting upon a disease, disorder, or condition with an agent to reduce or ameliorate harmful or any other undesired effects of the disease, disorder, or condition and/or its symptoms. 
     As used herein the term “effective amount” and the like in reference to an amount of a composition refers to an amount that is sufficient to induce a desired physiologic outcome (e.g., treatment of a disease). An effective amount can be administered in one or more administrations, applications or dosages. Such delivery is dependent on a number of variables including the time period which the individual dosage unit is to be used, the bioavailability of the composition, the route of administration, etc. It is understood, however, that specific amounts of the compositions (e.g., rAAV virions) for any particular subject depends upon a variety of factors including the activity of the specific agent employed, the age, body weight, general health, sex, and diet of the subject, the time of administration, the rate of excretion, the composition combination, severity of the particular disease being treated and form of administration. 
     The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. 
     The terms “individual,” “subject,” and “patient” are used interchangeably herein, and refer to a mammal, including, but not limited to, human and non-human primates (e.g., simians); mammalian sport animals (e.g., horses); mammalian farm animals sheep, goats, etc.); mammalian pets (e.g., dogs, cats, etc.); and rodents (e.g., mice, rats, etc.). 
     As used herein, the term “cardiomyopathy” refers to any disease or dysfunction that affects myocardium directly. The etiology of the disease or disorder may be, for example, inflammatory, metabolic, toxic, infiltrative, fibroplastic, hematological, genetic, or unknown in origin. Two fundamental forms are recognized (1) a primary type, consisting of heart muscle disease of unknown cause; and (2) a secondary type, consisting of myocardial disease of known cause or associated with a disease involving other organ systems. “Specific cardiomyopathy” refers to heart diseases associated with certain systemic or cardiac disorders; examples include hypertensive and metabolic cardiornyopathy. The cardiomyopathies include dilated cardiomyopathy (DCM), a disorder in which left and/or right ventricular systolic pump function is impaired, leading to progressive cardiac enlargement; hypertrophic cardiomyopathy, characterized by left ventricular hypertrophy without obvious causes such as hypertension or aortic stenosis; and restrictive cardiomyopathy, characterized by abnormal diastolic function and excessively rigid ventricular walls that impede ventricular filling. Cardiomyopathies also include left ventricular non-compaction, arrhythmogenic right ventricular cardiomyopathy, and arrhythmogenic right ventricular dysplasia. 
     “Heart failure” refers to the pathological state in which an abnormality of cardiac function is responsible for failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues and/or allows the heart to do so only from an abnormally elevated diastolic volume. Heart failure includes systolic and diastolic failure. Patients with heart failure are classified into those with low cardiac output (typically secondary to ischemic heart disease, hypertension, dilated cardiomyopathy, and/or valvular or pericardial disease) and those with elevated cardiac output (typically due to hyperthyroidism, anemia, pregnancy, arteriovenous fistulas, beriberi, and Paget&#39;s disease). Heart failure includes heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). 
     The term “therapeutic gene” as used herein refers to a gene that, when expressed, confers a beneficial effect on the cell or tissue in which it is present, or on a mammal in which the gene is expressed. Examples of beneficial effects include amelioration of a sign or symptom of a condition or disease, prevention or inhibition of a condition or disease, or conferral of a desired characteristic. Therapeutic genes include genes that partially or wholly correct a genetic deficiency in a cell or mammal. 
     As used herein the term “cardiac cell” refers to any cell present in the heart that provides a cardiac function, such as heart contraction or blood supply, or otherwise serves to maintain the structure of the heart. Cardiac cells as used herein encompass cells that exist in the epicardium, myocardium or endocardium of the heart. Cardiac cells also include, for example, cardiac muscle cells or cardiomyocytes, and cells of the cardiac vasculatures, such as cells of a coronary artery or vein. Other non-limiting examples of cardiac cells include epithelial cells, endothelial cells, fibroblasts, cardiac stem or progenitor cells, cardiac conducting cells and cardiac pacemaking cells that constitute the cardiac muscle, blood vessels and cardiac cell supporting structure. Cardiac cells may be derived from stem cells, including, for example, embryonic stem cells or induced pluripotent stem cells. 
     Expression Cassettes 
     Expression Cassette Overview 
     The vectors of the disclosure may comprise any expression cassette described herein. In some aspects, the rAAV virions of the disclosure comprise a viral genome comprising an expression cassette as shown in  FIG.  1   ,  FIGS.  7 A- 7 C , or variations thereof. The expression cassette may comprise a polynucleotide encoding any gene product described herein, or functional variant thereof, optionally operatively linked to a promoter, optionally an intron, optionally a polyadenylation (poly(A)) signal, optionally a woodchuck hepatitis virus post-transcriptional element (WPRE), and optionally a transcription termination signal. The expression cassette may be flanked by inverted terminal repeats (ITRs). These components provide the function of expressing the transgene after a host cell is targeted by, e.g., the rAAV virion. The promoter sequence, when present, controls expression of the polynucleotide encoding a gene product. 
     The expression cassette may comprise a polynucleotide encoding a DWORF polypeptide, or functional variant thereof, optionally operably linked to a promoter, optionally an intron, optionally a polyadenylation (poly(A)) signal, optionally a woodchuck hepatitis virus post-transcriptional element (WPRE), and optionally a transcription termination signal. The promoter sequence, when present, controls expression of the polynucleotide encoding the DWORF polypeptide, or functional variant thereof. The promoter sequence can be a cardiac cell-specific promoter. The promoter sequence can be further operably linked to an enhancer, such as any cardiac cell-specific enhancer described herein. 
     In any constructs shown in  FIG.  1    and  FIGS.  7 A- 7 C , DWORF nucleotide sequence can be replaced by a nucleotide sequence encoding another gene product or polypeptide, such as any gene product or polypeptide described herein (e.g., see the description of transgenes and gene products encoded by such transgenes below). Accordingly, in some embodiments, provided herein is any expression cassette shown in  FIG.  1    and  FIGS.  7 A- 7 C  wherein the DWORF nucleotide sequence is replaced by a nucleotide sequence encoding another gene product or polypeptide. 
     Also, in any expression cassettes shown in Table 1, DWORF nucleotide sequence can be replaced by a nucleotide sequence encoding another gene product or polypeptide, such as any gene product or polypeptide described herein (e.g., see the description of transgenes and gene products encoded by such transgenes below). Further, in any expression cassette shown in Table 1, the ITR sequences can be omitted. Accordingly, in some embodiments, provided herein is any expression cassette shown in Table 1 wherein the DWORF nucleotide sequence is replaced by a nucleotide sequence encoding another gene product or polypeptide, and/or wherein the specified ITR sequence is not present. 
     Transgenes 
     In some embodiments, the expression cassette of the disclosure comprises a transgene. Transgenes can include nucleotide sequences encoding any polypeptide for use in treating or preventing a heart disease or disorder, or alleviating symptoms therefrom. The promoters, enhancers and combinations thereof described herein are operably linked to a transgene encoding a product. A transgene can be a gene or nucleotide sequence that encodes a product, or functional fragment thereof. A product can be, for example, a polypeptide or a non-coding nucleotide. By non-coding nucleotide, it is meant that the sequence transcribed from the transgene or nucleotide sequence is not translated into a polypeptide. In some embodiments, the product encoded by the transgene or nucleotide operably linked to an enhancer described herein is a non-coding polynucleotide. A non-coding polynucleotide can be an RNA, such as for example a microRNA (miRNA or mIR), short hairpin RNA (shRNA), long non-coding RNA (lnRNA), and/or a short interfering RNA (siRNA). In some embodiments, the transgene encodes a product natively expressed by a cardiac cell, e.g., a cardiomyocyte. In some embodiments, the transgene encodes a product natively expressed in a cell type other than a cardiac cell. Without limitation, cell types other than cardiac fibroblasts can be from any multicellular organism, single-celled organism, or microorganism. 
     In some embodiments, the transgene encodes a polypeptide. In some embodiments, the transgene encodes a non-coding polynucleotide such as, for example, a microRNA (miRNA or mIR). 
     In some embodiments, the transgene comprises a sequence encoding a product selected from cadherins, connexins, Cx43, growth factors such as fibroblast growth factor (FGF)-2 and transforming growth factor-β, cytokines such as interleukin (IL)-1β and the IL-6 family, leukemia inhibitory factor, cardiotrophin-1, cardiogenic transcription factors, insulin-like growth factor, GATA4, MEF2C, TBX5, ESRRG, MESP1, MYOCD, ZFPM2, HAND2, miR-1, miR-133, Oct4, Sox2, Klf4, c-Myc, SRF, SMARCD3, Nkx2-5, Akt, PKB, Baf60c, BMP4, miR-208, and miR-499. 
     In some embodiments, the transgene encodes a functional cardiac protein. In some embodiments, the gene product is a genome-editing endonuclease (optionally with a guide RNA, single-guide RNA, and/or repair template) that replaces or repairs a non-functional cardiac protein into a functional cardiac protein. Functional cardiac proteins include, but are not limited to cardiac troponin T; a cardiac sarcomeric protein; β-myosin heavy chain; myosin ventricular essential light chain 1; myosin ventricular regulatory light chain 2; cardiac a-actin; a-tropomyosin; cardiac troponin 1; cardiac myosin binding protein C; four-and-a-half LIM protein 1; titin; 5′-AMP-activated protein kinase subunit gamma-2; troponin I type 3, myosin light chain 2, actin alpha cardiac muscle 1; cardiac LIM protein; caveolin 3 (CAV3); galactosidase alpha (GLA); lysosomal-associated membrane protein 2 (LAMP2); mitochondrial transfer RNA glycine (MTTG); mitochondrial transfer RNA isoleucine (MTTI); mitochondrial transfer RNA lysine (MTTK); mitochondrial transfer RNA glutamine (MTTQ); myosin light chain 3 (MYL3); troponin C (TNNC1); transthyretin (TTR); sarcoendoplasmic reticulum calcium-ATPase 2a (SERCA2a); stromal-derived factor-1 (SDF-1); adenylate cyclase-6 (AC6); beta-ARKct (β-adrenergic receptor kinase C terminus); fibroblast growth factor (FGF); platelet-derived growth factor (PDGF); vascular endothelial growth factor (VEGF); hepatocyte growth factor; hypoxia inducible growth factor; thymosin beta 4 (TMSB4X); nitric oxide synthase-3 (NOS3); unocartin 3 (UCN3); melusin; apoplipoprotein-E (ApoE); superoxide dismutase (SOD); and S100A1 (a small calcium binding protein; see, e.g., Ritterhoff and Most (2012)  Gene Ther.  19:613; Kraus et al. (2009)  Mol. Cell. Cardiol.  47:445). 
     In some embodiments, the transgene can treat or prevent coronary heart disease. In some embodiments, the transgene comprises a sequence encoding a product selected from vascular endothelial growth factor (VEGF), a VEGF isoform, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-D dNdC , VEGF-A 116A , VEGF-A 165 , VEGF-A 121 , VEGF-2, placenta growth factor (PIGF), fibroblast growth factor 4 (FGF-4), human growth factor (HGF), human granulocyte colony-stimulating factor (hGCSF), and hypoxia inducible factor 1α (HIF-1α). 
     In some embodiments, the transgene can treat or prevent heart failure. In some embodiments, the transgene can treat or prevent chronic heart failure. In some embodiments, the transgene comprises a sequence encoding a product selected from SERCA2a, stromal cell-derived factor-1 (SDF-1), adenylyl cyclase type 6, S100A1, miRNA-17-92, miR-302-367, anti-miR-29a, anti-miR-30a, antimiR-141, cyclin A2, cyclin-dependent kinase 2, Tbx20, miRNA-590, miRNA-199, anti-sense oligonucleotide against Lp(a), interfering RNA against PCSK9, anti-sense oligonucleotide against apolipoprotein C-III, lipoprotein lipase S447X , anti-sense oligonucleotide against apolipoprotein B, anti-sense oligonucleotide against c-myc, and E2F oligonucleotide decoy. 
     In some embodiments, the transgene encodes a gene product whose expression complements a defect in a gene responsible for a genetic disorder. The disclosure polynucleotides encoding one or more of the following—e.g., for use, without limitation, in the disorder indicated in parentheses, or for other disorders caused by each: TAZ (Barth syndrome); FXN (Freidrich&#39;s Ataxia); CASQ2 (CPVT); FBN1 (Marfan); RAF1 and SOS1s (Noonan); SCN5A (Brugada); KCNQ1 and KCNH2s (Long QT Syndrome); DMPK (Myotonic Dystrophy 1); LMNA (Limb Girdle Dystrophy Type 1B); JUP (Naxos); TGFBR2 (Loeys-Dietz); EMD (X-Linked EDMD); and ELN (SV Aortic Stenosis). In some embodiments, a polynucleotide encodes one or more of: cardiac troponin T (TNNT2); BAG family molecular chaperone regulator 3 (BAG3); myosin heavy chain (MYH7); tropomyosin 1 (TPM1), myosin binding protein C (MYBPC3); 5′-AMP-activated protein kinase subunit gamma-2 (PRKAG2); troponin I type 3 (TNNI3); titin (TTN); myosin, light chain 2 (MYL2); actin, alpha cardiac muscle 1 (ACTC1); potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1); myocyte enhancer factor 2c (MEF2C); and cardiac LIM protein (CSRP3). 
     In some embodiments, the transgene comprises a nucleotide sequence encoding a protein selected from DWORF, junctophilin (e.g., JPH2), BAG family molecular chaperone regulator 3 (BAG3), phospholamban (PLN), alpha-crystallin B chain (CRYAB), LMNA (such as Lamin A and Lamin C isoforms), troponin I type 3 (TNNI3), lysosomal-associated membrane protein 2 (LAMP2, such as LAMP2a, LAMP2b and LAMP2c isoforms), desmoplakin (DSP, such as DPI and DPII isoforms), desmoglein 2 (DSG2), and junction pla.koglobin (JUP). In some embodiments, the transgene comprises a nucleotide sequence encoding a human protein. In some embodiments, the transgene comprises a human nucleotide sequence (a human DNA sequence). In some embodiments, the transgene comprises a DNA sequence that has been codon-optimized. In some embodiments, the transgene comprises a nucleotide sequence encoding a wild-type protein, or a functionally active fragment thereof. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a DWORF polypeptide. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a junctophilin 2 (JPH2) polypeptide. In some embodiments, the transgene comprises a polynucleotide sequence encoding a full-length JPH2 polypeptide. In some embodiments, the transgene comprises a polynucleotide sequence encoding an N-terminal fragment of the JPH2 polypeptide. In some embodiments, the transgene comprises a polynucleotide sequence encoding an N-terminal fragment of the JPH2 polypeptide, which retains the JPH2 activity. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a BAG3 polypeptide. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a CRYAB polypeptide. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a LMNA polypeptide. In some embodiments, the transgene comprises a polynucleotide sequence encoding the LaminA isoform of LMNA. In some embodiments, the transgene comprises a polynucleotide sequence encoding the LaminC isoform of LMNA. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a TNNI3 polypeptide. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a PLN polypeptide. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a LAMP2 polypeptide. In some embodiments, the transgene comprises a polynucleotide sequence encoding the LAMP2a isoform. In some embodiments, the transgene comprises a polynucleotide sequence encoding the LAMP2b isoform. In some embodiments, the transgene comprises a polynucleotide sequence encoding the LAMP2c isoform. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a DSP polypeptide. In some embodiments, the transgene comprises a polynucleotide sequence encoding the DPI isoform of DSP. In some embodiments, the transgene comprises a polynucleotide sequence encoding the DPI isoform of DSP. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a DSG2 polypeptide. 
     In some embodiments, the transgene comprises a polynucleotide sequence encoding a JUP polypeptide. 
     It is appreciated that the transgenes described herein are non-limiting and transgenes useful for treating a heart disease may be discovered for use in the expression cassettes described herein. 
     DWORF Transgene 
     In some embodiments, the expression cassette of the present disclosure comprises a polynucleotide sequence encoding a DWORF polypeptide. In some embodiments, the expression cassette provides increased expression of a DWORF polypeptide in cardiac cell. In some embodiments, the cardiac cell is a cardiomyocyte. In some embodiments, expression of the DWORF polypeptide may be increased 5%, 10%, 15%, 20%, or 25% compared to expression of the DWORF polypeptide factor in an untreated subject. In some embodiments, expression of the DWORF polypeptide may be increased 1-fold, 2-fold, 3-fold, 4-fold, or 5-fold compared to expression of the DWORF polypeptide in an untreated subject. In some embodiments, the DWORF polypeptide may be expressed at any detectable level in the cardiac cell, whereas the DWORF polypeptide may not be expressed, or expressed at undetectable levels, in an untreated subject. Put another way, the cardiac cell to which the rAAV virion is administered may express a DWORF polypeptide in higher abundance than in a cardiac cell that has only endogenous (i.e., native) expression of the DWORF polypeptide. 
     DWORF polypeptide is an endogenous enhancer of SERCA calcium pump activity, a desirable drug target for regulation of cardiac contractility. DWORF is also an unusually small protein, which makes it a good candidate for delivery to a target cell or tissue by rAAV virions. Because DWORF is an endogenous protein, expression of DWORF in humans would not be immunogenic, allowing for long-term dosing and expression. The structural features of DWORF polypeptides are as follows. First, the polypeptides may have 5 to 35 consecutive residues of the Dwarf Open Reading Frame (DWORF), located on chromosome 3 of a mammalian species, including mouse and human (Nelson et al.  Science.  351:271-275 (2016); U.S. Pat. No. 10,570,183). Thus, the term “a peptide having no more than X consecutive residues,” even when including the term “comprising,” cannot be understood to comprise a greater number of consecutive residues. In general, the peptides will be 35 residues or less, again, comprising no more than 20 consecutive residues of DWORF. The overall length may be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35 residues. Ranges of peptide length of 5-34/35 residues, 6-34/35 residues, 7-50 residues, 7-25, residues, 5-20 residues, 6-20 residues, 7-20 residues, and 7-15 residues are contemplated. The number of consecutive DWORF residues may be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Ranges of consecutive residues of 5-20 residues, 5-20 residues, 6-20 residues, 7-20 residues and 5-15 residues, 5-15, residues, 6-15 residues or 7-15 residues are contemplated. Illustrative DWORF sequences can be found in Table 2a. 
     In some embodiments, DWORF polypeptide is human DWORF polypeptide. In some embodiments, the expression cassette comprises a single polynucleotide sequence encoding a dwarf open reading frame (DWORF) polypeptide. In some embodiments, the polynucleotide sequence encoding DWORF is codon optimized. In some embodiments, the DWORF polypeptide comprises a polypeptide sequence that shares at least 95% identity to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, or SEQ ID NO: 9. In some embodiments, the DWORF polypeptide comprises a polypeptide sequence that shares at least 98% identity to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, or SEQ ID NO: 9. In some embodiments, the DWORF polypeptide comprises the polypeptide sequence of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, Or SEQ ID NO: 9. 
     
       
         
           
               
             
               
                 TABLE 2a 
               
             
            
               
                   
               
               
                 Illustrative DWORF Sequences 
               
            
           
           
               
               
               
            
               
                 DWORF 
                   
                   
               
               
                 Variant 
                 DWORF Polypeptide 
                 Nucleotide (Open Reading Frame) 
               
               
                   
               
               
                 Mouse 
                 MAEKESTSPHLMVPILLLVGWIV 
                 ATGGCTGAGAAAGAGTCAACATCACCACACCT 
               
               
                 Variant 
                 GCIIVIYIVFF (SEQ ID NO: 1) 
                 CATGGTTCCCATTCTTCTCCTGGTTGGATGGATT 
               
               
                   
                   
                 GTAGGCTGCATCATCGTTATTTACATTGTCTTCT 
               
               
                   
                   
                 TCTAA (SEQ ID NO: 2) 
               
               
                   
               
               
                 Human 
                 MAEKAGSTFSHLLVPILLLIGWIV 
                 ATGGCTGAAAAAGCGGGGTCTACATTTTCACAC 
               
               
                 Variant 
                 GCIIMIYVVFS (SEQ ID NO: 3) 
                 CTTCTGGTTCCTATTCTTCTCCTGATTGGCTGGA 
               
               
                   
                   
                 TTGTGGGCTGCATCATAATGATTTATGTTGTCTT 
               
               
                   
                   
                 CTCTTAG (SEQ ID NO: 4) 
               
               
                   
               
               
                 Artificial 
                 MAEKAESTSPHLMVPILLLVGWI 
                 ATGGCTGAGAAAGCAGAGTCAACATCACCACA 
               
               
                   
                 VGCIIVIYIVFF (SEQ ID NO: 5) 
                 CCTCATGGTTCCCATTCTTCTCCTGGTTGGATGG 
               
               
                   
                   
                 ATTGTAGGCTGCATCATCGTTATTTACATTGTCT 
               
               
                   
                   
                 TCTTCTAA (SEQ ID NO: 6) 
               
               
                   
               
               
                 Artificial 
                 MAEKESTSPHLIVPILLLVGWIVG 
                 ATGGCTGAGAAAGAGTCAACATCACCACACCT 
               
               
                   
                 CIIVIYIVFF (SEQ ID NO: 7) 
                 CATTGTTCCCATTCTTCTCCTGGTTGGATGGATT 
               
               
                   
                   
                 GTAGGCTGCATCATCGTTATTTACATTGTCTTCT 
               
               
                   
                   
                 TCTAA (SEQ ID NO: 8) 
               
               
                   
               
               
                 Artificial 
                 MAEKAESTSPHLIVPILLLVGWIV 
                 ATGGCTGAGAAAGCAGAGTCAACATCACCACA 
               
               
                   
                 GCIIVIYIVFF (SEQ ID NO: 9) 
                 CCTCATTGTTCCCATTCTTCTCCTGGTTGGATGG 
               
               
                   
                   
                 ATTGTAGGCTGCATCATCGTTATTTACATTGTCT 
               
               
                   
                   
                 TCTTCTAA (SEQ ID NO: 10) 
               
               
                   
               
               
                 Human 
                 MAEKESTSPHLMVPILLLVGWIV 
                 ATGGCAGAGAAGGCTGGAAGCACTTTCTCTCA 
               
               
                 Variant 
                 GCIIVIYIVFF (SEQ ID NO: 32) 
                 CCTGCTCGTGCCGATTTTGCTTTTGATTGGGTG 
               
               
                   
                   
                 GATAGTTGGCTGTATCATAATGATCTACGTTGT 
               
               
                   
                   
                 CTTTTCATAG (SEQ ID NO: 33) 
               
               
                   
               
               
                 Human 
                 MAEKGSTFSHLLVPILLLIGWIVG 
                 ATGGCCGAGAAGGGCAGCACCTTCAGCCACCT 
               
               
                 Variant 
                 CIIMIYVVFS (SEQ ID NO: 43) 
                 GCTGGTGCCCATCCTGCTGCTGATCGGCTGGAT 
               
               
                   
                   
                 CGTGGGCTGCATCATCATGATCTACGTGGTGTT 
               
               
                   
                   
                 CAGC (SEQ ID NO: 44) 
               
               
                   
               
               
                 Codon 
                 MAEKESTSPHLMVPILLLVGWIV 
                 ATGGCCGAGAAGGAATCTACCAGCCCCCACCT 
               
               
                 Optimized 
                 GCIIVIYIVFF (SEQ ID NO: 1) 
                 GATGGTGCCTATTCTGCTGCTGGTGGGCTGGAT 
               
               
                 Mouse 
                   
                 CGTCGGCTGCATCATCGTGATCTACATCGTGTT 
               
               
                 DWORF 
                   
                 CTTCTGA (SEQ ID NO: 76) 
               
               
                   
               
               
                 Codon 
                 MAEKAGSTFSHLLVPILLLIGWIV 
                 ATGGCCGAGAAGGCCGGATCTACCTTCAGCCA 
               
               
                 Optimized 
                 GCIIMIYVVFS (SEQ ID NO: 3) 
                 CCTGCTGGTCCCTATTCTGCTGCTGATCGGCTG 
               
               
                 Human 
                   
                 GATCGTGGGCTGCATCATCATGATCTACGTGGT 
               
               
                 DWORF 
                   
                 GTTCAGCTGA (SEQ ID NO: 77) 
               
               
                   
               
            
           
         
       
     
     Other Exemplary Transgenes 
     In some embodiments, the expression cassette of the present disclosure comprises a polynucleotide sequence encoding another gene product (not DWORF), for example, a polypeptide selected from JPH2, BAG3, CRYAB, LMNA (e.g., Lamin A or Lamin C isoform), TNNI3, PLN, LAMP2 (e.g., LAMP2a, LAMP2b or LAMP2c isoform), DSP (e.g., DPI or DPII isoform), desmoglein 2 (DSG2), and junction plakoglobin (JUP). In some embodiments, the expression cassette provides increased expression of the gene product in a cardiac cell. In some embodiments, the cardiac cell is a cardiomyocyte. In some embodiments, expression of the polypeptide encoded by the polynucleotide sequence may be increased 5%, 10%, 15%, 20%, or 25% compared to expression in an untreated subject. In some embodiments, expression of the polypeptide encoded by the polynucleotide sequence may be increased 1-fold, 2-fold, 3-fold, 4-fold, or 5-fold compared to expression in an untreated subject. In some embodiments, the polypeptide encoded by the polynucleotide sequence may be expressed at any detectable level in the cardiac cell, whereas it may not be expressed, or expressed at undetectable levels, in an untreated subject. In some embodiments, the cardiac cell to which a vector described herein is administered may express a polypeptide encoded by the polynucleotide sequence in higher abundance than in a cardiac cell that has only endogenous (i.e., native) expression of the polypeptide. 
     In some embodiments, the polypeptide is a human polypeptide. In some embodiments, the polynucleotide sequence encoding the polypeptide is codon optimized. In some embodiments, the expression cassette comprises a single polynucleotide sequence encoding a polypeptide. In some embodiments, the expression cassette comprises two polynucleotide sequences encoding a polypeptide. In some embodiments, the expression cassette comprises two polynucleotide sequences encoding a polypeptide, wherein at least one of the sequences is codon-optimized. 
     In some embodiments, a polynucleotide sequence encodes JPH2, e.g., human JPH2. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO: 201. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding JPH2, e.g., human JPH2. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is JPH2, e.g., human JPH2. In some embodiments, the JPH2 polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO: 202. 
     In some embodiments, a polynucleotide sequence encodes an N-terminal fragment of JPH2, e.g., human JPH2. In some embodiments, a polynucleotide sequence of an N-terminal fragment of JPH2 has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:227. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding an N-terminal fragment of JPH2, e.g., human JPH2. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is an N-terminal fragment of JPH2, e.g., human JPH2. In some embodiments, the N-terminal fragment of JPH2 polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:228. The human sequences of an N-terminal fragment of JPH2 correspond to the mouse JPH2 N-terminal peptide with amino acids 1-565, generated by a Calpain cleavage (see Guo et al., 2018, Science 362, doi: 10.1126/science.aan3303). 
     In some embodiments, a polynucleotide sequence encodes BAG3, e.g., human BAG3. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:203. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding BAG3, e.g., human BAG3. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is BAG3, e.g., human BAG3. In some embodiments, the BAG3 polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:204. 
     In some embodiments, a polynucleotide sequence encodes CRYAB, e,g., human CRYAB. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:205. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding CRYAB, e.g., human CRYAB. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is CRYAB, e.g,, human CRYAB. In some embodiments, the CRYAB polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:206. 
     In some embodiments, a polynucleotide sequence encodes LMNA, e.g., human LMNA. In some embodiments, a polynucleotide sequence encodes Lamin A isoform of LMNA, e.g., human Lamin A. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:207. In some embodiments, a polynucleotide sequence encodes Lamin C isoform of LMNA, e.g., human Lamin C. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:209. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding an LMNAA polypeptide. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding Lamin A or Lamin C, e.g., human Lamin A or Lamin C. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is LMNA, e.g., human LMNA. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is Lamin A isoform of LMNA, e.g., human. In some embodiments, the Lamin A polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:208. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is Lamin C isoform of LMNA, e.g., human. In some embodiments, the Lamin C polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:210. 
     In some embodiments, a polynucleotide sequence encodes TNNI3, e.g., human TNNI3. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:211. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding TNNI3, e.g., human TNNI3. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is TNNI3, e.g., human TNNI3. In some embodiments, the TNNI3 polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:212. 
     In some embodiments, a polynucleotide sequence encodes PLN, e.g., human PLN. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:229. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding PLN, e.g., human PLN. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is PLN, e.g., human PLN. In some embodiments, the PLN polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:230. 
     In some embodiments, a polynucleotide sequence encodes LAMP2, e.g., human LAMP2. In some embodiments, a polynucleotide sequence encodes LAMP2a isoform of LAMP2, e.g., human LAMP2a. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:213. In some embodiments, a polynucleotide sequence encodes LAMP2b isoform of LAMP, e.g., human LAMP2b. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:215. In some embodiments, a polynucleotide sequence encodes LAMP2c isoform of LAMP, e.g., human LAMP2c. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:217. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding LAMP2, e.g., human LAMP2. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding LAMP2a, LAMP2b or LAMP2c. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is a LAMP2 polypeptide, e.g., human LAMP2. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is LAMP2a isoform of LAMP2, e.g., human. In some embodiments, the LAMP2a polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:214. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is LAMP2b isoform of LAMP2, e.g., human. In some embodiments, the LAMP2b polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:216. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is LAMP2c isoform of LAMP2, e.g., human. In some embodiments, the LAMP2c polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:218. 
     In some embodiments, a polynucleotide sequence encodes DSP, e.g., human DSP. In some embodiments, a polynucleotide sequence encodes DPI isoform of DSP, e.g., human DPI. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:219. In some embodiments, a polynucleotide sequence encodes DPII isoform of DSP, e.g., human DPII. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:221. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding a DSP polypeptide. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding DPI or DPII, e.g., human DPI or DPII. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is DSP, e.g., human DSP. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is DPI isoform of DSP, e.g., human. In some embodiments, the DPI polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:220. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is DPII isoform of DSP, e.g., human. In some embodiments, the DPII polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:222. 
     In some embodiments, a polynucleotide sequence encodes DSG2, e.g., human DSG2. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:223. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding DSG2, e.g., human DSG2. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is DSG2, e.g., human DSG2. In some embodiments, the DSG2 polypeptide has at least 75%, 80%, 85%, 90%, 95% 98%, 99% or 100% sequence identity to SEQ ID NO:224. 
     In some embodiments, a polynucleotide sequence encodes JUP, e.g., human JUP. In some embodiments, a polynucleotide sequence has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:225. In some embodiments, a polynucleotide sequence is a codon-optimized sequence encoding JUP, e.g., human JUP. In some embodiments, the gene product or polypeptide expressed using any expression construct described herein is JUP, e.g., human JUP. In some embodiments, the JUP polypeptide has at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO:226. 
     In some embodiments, any other polynucleotide sequence described herein can be used in any expression construct described herein. In some embodiments, such polynucleotide sequence encodes any gene product or polypeptide described herein. The polynucleotide sequence can be sequence-optimized (such as for expression in a human). In some embodiments, the sequence encodes a human polypeptide. The sequences of the polynucleotides and polypeptides described herein are known in the art. Sequences that have at least 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to such sequence are also contemplated herein. Illustrative sequences can be found in Table 2b. 
     
       
         
           
               
             
               
                 TABLE 2b 
               
             
            
               
                   
               
               
                 Illustrative Gene product Sequences 
               
            
           
           
               
               
               
            
               
                 Transgene 
                 Polypeptide 
                 Nucleotide (Open Reading Frame) 
               
               
                   
               
               
                 Human 
                 
                   MSGGRFDFDDGGAYCGGWEG 
                 
                 
                   ATGAGTGGGGGCCGCTTCGACTTTGATGATG 
                 
               
               
                 JPH2 
                 
                   GKAHGHGLCTGPKGQGEYSGS 
                 
                 
                   GAGGGGCGTACTGCGGGGGCTGGGAGGGG 
                 
               
               
                 (the N- 
                 
                   WNFGFEVAGVYTWPSGNTFEG 
                 
                 
                   GGAAAGGCCCATGGGCATGGACTGTGCACA 
                 
               
               
                 terminal 
                 
                   YWSQGKRHGLGIETKGRWLYK 
                 
                 
                   GGCCCCAAGGGCCAGGGCGAATACTCTGGC 
                 
               
               
                 part of the 
                 
                   GEWTHGFKGRYGIRQSSSSGAK 
                 
                 
                   TCCTGGAACTTTGGCTTTGAGGTGGCAGGTG 
                 
               
               
                 sequence 
                 
                   YEGTWNNGLQDGYGTETYADG 
                 
                 
                   TCTACACCTGGCCCAGCGGAAACACCTTTGA 
                 
               
               
                 that, in 
                 
                   GTYQGQFTNGMRHGYGVRQSV 
                 
                 
                   GGGATACTGGAGCCAGGGCAAACGGCATGG 
                 
               
               
                 some 
                 
                   PYGMAVVVRSPLRTSLSSLRSE 
                 
                 
                   GCTGGGCATAGAGACCAAGGGGCGCTGGCT 
                 
               
               
                 instances, 
                 
                   HSNGTVAPDSPASPASDGPALPS 
                 
                 
                   CTACAAGGGCGAGTGGACACATGGCTTCAA 
                 
               
               
                 can be used 
                 
                   PAIPRGGFALSLLANAEAAARAP 
                 
                 
                   GGGACGCTACGGAATCCGGCAGAGCTCAAG 
                 
               
               
                 on its own, 
                 
                   KGGGLFQRGALLGKLRRAESR 
                 
                 
                   CAGCGGTGCCAAGTATGAGGGCACCTGGAA 
                 
               
               
                 as an 
                 
                   TSVGSQRSRVSFLKSDLSSGASD 
                 
                 
                   CAATGGCCTGCAAGACGGCTATGGCACCGA 
                 
               
               
                 alternative 
                 
                   AASTASLGEAAEGADEAAPFEA 
                 
                 
                   GACCTATGCTGATGGAGGGACGTACCAAGG 
                 
               
               
                 to the full- 
                 
                   DIDATTTETYMGEWKNDKRSG 
                 
                 
                   CCAGTTCACCAACGGCATGCGCCATGGCTAC 
                 
               
               
                 length 
                 
                   FGVSERSSGLRYEGEWLDNLRH 
                 
                 
                   GGAGTACGCCAGAGCGTGCCCTACGGGATG 
                 
               
               
                 JPH2, is 
                 
                   GYGCTTLPDGHREEGKYRHNV 
                 
                 
                   GCCGTGGTGGTGCGCTCGCCGCTGCGCACG 
                 
               
               
                 shown in 
                 
                   LVKDTKRRMLQLKSNKVRQKV 
                 
                 
                   TCGCTGTCGTCCCTGCGCAGCGAGCACAGC 
                 
               
               
                 bold) 
                 
                   EHSVEGAQRAAAIARQKAEIAA 
                 
                 
                   AACGGCACGGTGGCCCCGGACTCTCCCGCC 
                 
               
               
                   
                 
                   SRTSHAKAKAEAAEQAALAAN 
                 
                 
                   TCGCCGGCCTCCGACGGCCCCGCGCTGCCC 
                 
               
               
                   
                 
                   QESNIARTLARELAPDFYQPGPE 
                 
                 
                   TCGCCCGCCATCCCGCGTGGCGGCTTCGCG 
                 
               
               
                   
                 
                   YQKRRLLQEILENSESLLEPPDR 
                 
                 
                   CTCAGCCTCCTGGCCAATGCCGAGGCGGCC 
                 
               
               
                   
                 
                   GAGAAGLPQPPRESPQLHERET 
                 
                 
                   GCGCGGGCGCCCAAGGGCGGCGGCCTCTTC 
                 
               
               
                   
                 
                   PRPEGGSPSPAGTPPQPKRPRPG 
                 
                 
                   CAGCGGGGCGCGCTGCTGGGCAAGCTGCGG 
                 
               
               
                   
                 
                   VSKDGLLSPGAWNGEPSGEGSR 
                 
                 
                   CGCGCAG 
                 
               
               
                   
                 
                   SVTPSEGAGRRSPARPATERMAI 
                 
                 
                   AGTCGCGCACGTCCGTGGGTAGCCAGCGCA 
                 
               
               
                   
                 
                   EALQAPPAPSREPEVALYQGYH 
                 
                 
                   GCCGTGTCAGCTTCCTTAAGAGCGACCTCAG 
                 
               
               
                   
                   SYAVRT TPPEPPPFEDQPEPEVSGS 
                 
                   CTCGGGCGCCAGCGACGCCGCGTCCACCGC 
                 
               
               
                   
                 ESAPSSPATAPLQAPTLRGPEPAR 
                 
                   CAGCCTGGGAGAGGCCGCCGAGGGCGCCGA 
                 
               
               
                   
                 ETPAKLEPKPIIPKAEPRAKARKTE 
                 
                   CGAGGCCGCACCCTTCGAGGCCGATATCGA 
                 
               
               
                   
                 ARGLTKAGAKKKARKEAALAAE 
                 
                   CGCCACCACCACCGAGACCTACATGGGCGA 
                 
               
               
                   
                 AEVEVEEVPNTILICMVILLNIGLA 
                 
                   GTGGAAGAACGACAAACGCTCGGGCTTCGG 
                 
               
               
                   
                 ILFVHLLT (SEQ ID NO: 202) 
                 
                   CGTGAGCGAACGCTCCAGTGGCCTCCGCTA 
                 
               
               
                   
                   
                 
                   CGAGGGCGAGTGGCTGGACAACCTGCGCCA 
                 
               
               
                   
                   
                 
                   CGGCTATGGCTGCACCACGCTGCCCGACGG 
                 
               
               
                   
                   
                 
                   CCACCGCGAGGAGGGCAAGTACCGCCACAA 
                 
               
               
                   
                   
                 
                   CGTGCTGGTCAAGGACACCAAGCGCCGCAT 
                 
               
               
                   
                   
                 
                   GCTGCAGCTCAAGAGCAACAAGGTCCGCCA 
                 
               
               
                   
                   
                 
                   GAAAGTGGAGCACAGTGTGGAGGGTGCCCA 
                 
               
               
                   
                   
                 
                   GCGCGCCGCTGCTATCGCGCGCCAGAAGGC 
                 
               
               
                   
                   
                 
                   CGAGATTGCCGCCTCCAGGACAAGCCACGC 
                 
               
               
                   
                   
                 
                   CAAGGCCAAAGCTGAGGCAGCGGAACAGGC 
                 
               
               
                   
                   
                 
                   CGCCCTGGCTGCCAACCAGGAGTCCAACATT 
                 
               
               
                   
                   
                 
                   GCTCGCACTTTGGCCAGGGAGCTGGCTCCG 
                 
               
               
                   
                   
                 
                   GACTTCTACCAGCCAGGTCCGGAATATCAGA 
                 
               
               
                   
                   
                 
                   AGCGCCGGCTGCTGCAGGAGATCCTGGAGA 
                 
               
               
                   
                   
                 
                   ACTCGGAGAGCCTGCTGGAGCCCCCCGACC 
                 
               
               
                   
                   
                 
                   GGGGCGCCGGCGCAGCGGGCCTCCCACAGC 
                 
               
               
                   
                   
                 
                   CGCCCCGCGAGAGCCCGCAGCTGCACGAGC 
                 
               
               
                   
                   
                 
                   GTGAGACCCCTCGGCCCGAGGGTGGCTCCC 
                 
               
               
                   
                   
                 
                   CGTCACCGGCCGGGACGCCCCCGCAGCCCA 
                 
               
               
                   
                   
                 
                   AGCGGCCCAGGCCCGGGGTGTCCAAGGACG 
                 
               
               
                   
                   
                 
                   GCCTGCTGAGCCCAGGCGCCTGGAACGGCG 
                 
               
               
                   
                   
                 
                   AGCCCAGCGGTGAGGGCAGCCGGTCAGTCA 
                 
               
               
                   
                   
                 
                   CTCCGTCCGAGGGCGCGGGCCGCCGCAGCC 
                 
               
               
                   
                   
                 
                   CCGCGCGTCCAGCCACCGAGCGCATGGCCA 
                 
               
               
                   
                   
                 
                   TCGAGGCTCTGCAGGCACCGCCTGCGCCGT 
                 
               
               
                   
                   
                 
                   CGCGGGAGCCGGAGGTGGCGCTTTACCAGG 
                 
               
               
                   
                   
                   GCTACCACAGCTATGCTGTGCGC ACCACGCC 
               
               
                   
                   
                 GCCCGAGCCCCCACCCTTTGAGGACCAGCCCG 
               
               
                   
                   
                 AGCCCGAGGTCTCCGGGTCCGAGTCCGCGCCCT 
               
               
                   
                   
                 CGTCCCCGGCCACCGCCCCGCTGCAGGCCCCOA 
               
               
                   
                   
                 CGCTCCGAGGCCCCGAGCCTGCACGCGAGACC 
               
               
                   
                   
                 CCCGCCAAGCTGGAGCCCAAGCCCATCATCCCC 
               
               
                   
                   
                 AAAGCCGAGCCCAGGGCCAAGGCCCGCAAGAC 
               
               
                   
                   
                 TGAGGCTCGAGGGCTGACCAAGGCGGGGGCCA 
               
               
                   
                   
                 AGAAGAAGGCGCGGAAGGAGGCCGCACTGGC 
               
               
                   
                   
                 GGCAGAGGCGGAGGTGGAGGTGGAAGAGGTCC 
               
               
                   
                   
                 CCAACACCATCCTCATCTGCATGGTGATCCTGC 
               
               
                   
                   
                 TGAACATCGGCCTGOCCATCCTCTTTGTTCACC 
               
               
                   
                   
                 TCCTGACCTGA (SEQ ID NO: 201) 
               
               
                   
               
               
                 Human 
                 MSAATHSPMMQVASGNGDRDPL 
                 ATGAGCGCCGCCACCCACTCGCCCATGATGCA 
               
               
                 BAG3 
                 PPGWEIKIDPQTGWPFFVDHNSRT 
                 GGTGGCGTCCGGCAACGGTGACCGCGACCCTTT 
               
               
                   
                 TTWNDPRVPSEGPKETPSSANGPS 
                 GCCCCCCGGATGGGAGATCAAGATCGACCCGC 
               
               
                   
                 REGSRLPPAREGHPVYPQLRPGYI 
                 AGACCGGCTGGCCCTTCTTCGTGGACCACAACA 
               
               
                   
                 PIPVLHEGAENRQVHPFHVYPQPG 
                 GCCGCACCACTACGTGGAACGACCCGCGCGTG 
               
               
                   
                 MQRFRTEAAAAAPQRSQSPLRGM 
                 CCCTCTGAGGGCCCCAAGGAGACTCCATCCTCT 
               
               
                   
                 PETTQPDKQCGQVAAAAAAQPPA 
                 GCCAATGGCCCTTCCCGGGAGGGCTCTAGGCTG 
               
               
                   
                 SHGPERSQSPAASDCSSSSSSASLP 
                 CCGCCTGCTAGGGAAGGCCACCCTGTGTACCCC 
               
               
                   
                 SSGRSSLGSHQLPRGYISIPVIHEQ 
                 CAGCTCCGACCAGGCTACATTCCCATTCCTGTG 
               
               
                   
                 NVTRPAAQPSFHQAQKTHYPAQQ 
                 CTCCATGAAGGCGCTGAGAACCGGCAGGTGCA 
               
               
                   
                 GEYQTHQPVYHKIQGDDWEPRPL 
                 CCCTTTCCATGTCTATCCCCAGCCTGGGATGCA 
               
               
                   
                 RAASPFRSSVQGASSREGSPARSS 
                 GCGATTCCGAACTGAGGCGGCAGCAGCGGCTC 
               
               
                   
                 TPLHSPSPIRVHTVVDRPQQPMTH 
                 CTCAGAGGTCCCAGTCACCTCTGCGGGGCATGC 
               
               
                   
                 RETAPVSQPENKPESKPGPVGPEL 
                 CAGAAACCACTCAGCCAGATAAACAGTGTGGA 
               
               
                   
                 PPGHIPIQVIRKEVDSKPVSQKPPP 
                 CAGGTGGCAGCGGCGGCGGCAGCCCAGCCCCC 
               
               
                   
                 PSEKVEVKVPPAPVPCPPPSPGPS 
                 AGCCTCCCACGGACCTGAGCGGTCCCAGTCTCC 
               
               
                   
                 AVPSSPKSVATEERAAPSTAPAEA 
                 AGCTGCCTCTGACTGCTCATCCTCATCCTCCTC 
               
               
                   
                 TPPKPGEAEAPPKHPGVLKVEAIL 
                 GGCCAGCCTGCCTTCCTCCGGCAGCAGCAGCCT 
               
               
                   
                 EKVQGLIQAVDNFEGKKTDKKY 
                 GGGCAGTCACCAGCTCCCGCGGGGGTACATCT 
               
               
                   
                 LMIEEYLTKELLALDSVDPEGRA 
                 CCATTCCGGTGATACACGAGCAGAACGTTACCC 
               
               
                   
                 DVRQARRDGVRKVQTILEKLEQK 
                 GGCCAGCAGCCCAGCCCTCCTTCCACCAAGCCC 
               
               
                   
                 AIDVPGQVQVYELQPSNLEADQP 
                 AGAAGACGCACTACCCAGCGCAGCAGGGGGAG 
               
               
                   
                 LQAIMEMGAVAADKGKKNAGN 
                 TACCAGACCCACCAGCCTGTGTACCACAAGATC 
               
               
                   
                 AEDPHTETQQPEATAAATSNPSS 
                 CAGGGGGATGACTGGGAGCCCCGGCCCCTGCG 
               
               
                   
                 MTDTPGNPAAP (SEQ ID NO: 204) 
                 GGCGGCATCCCCGTTCAGGTCATCTGTCCAGGG 
               
               
                   
                   
                 TGCATCGAGCCGGGAGGGCTCACCAGCCAGGA 
               
               
                   
                   
                 GCAGCACGCCACTCCACTCCCCCTCGCCCATCC 
               
               
                   
                   
                 GTGTGCACACCGTGGTCGACAGGCCTCAGCAG 
               
               
                   
                   
                 CCCATGACCCATCGAGAAACTGCACCTGTTTCC 
               
               
                   
                   
                 CAGCCTGAAAACAAACCAGAAAGTAAGCCAGG 
               
               
                   
                   
                 CCCAGTTGGACCAGAACTCCCTC 
               
               
                   
                   
                 CTGGACACATCCCAATTCAAGTGATCCGCAAA 
               
               
                   
                   
                 GAGGTGGATTCTAAACCTGTTTCCCAGAAGCCC 
               
               
                   
                   
                 CCACCTCCCTCTGAGAAGGTAGAGGTGAAAGT 
               
               
                   
                   
                 TCCCCCTGCTCCAGTTCCTTGTCCTCCTCCCAGC 
               
               
                   
                   
                 CCTGGCCCTTCTGCTGTCCCCTCTTCCCCCAAG 
               
               
                   
                   
                 AGTGTGGCTACAGAAGAGAGGGCAGCCCCCAG 
               
               
                   
                   
                 CACTGCCCCTGCAGAAGCTACACCTCCAAAACC 
               
               
                   
                   
                 AGGAGAAGCCGAGGCTCCCCCAAAACATCCAG 
               
               
                   
                   
                 GAGTGCTGAAAGTGGAAGCCATCCTGGAGAAG 
               
               
                   
                   
                 GTACAGGGGCTGGAGCAGGCTGTAGACAACTT 
               
               
                   
                   
                 TGAAGGCAAGAAGACTGACAAAAAG 
               
               
                   
                   
                 TACCTGATGATCGAAGAGTATTTGACCAAAGA 
               
               
                   
                   
                 GCTGCTGGCCCTGGATTCAGTGGACCCCGAGG 
               
               
                   
                   
                 GACGAGCCGATGTGCGTCAGGCCAGGAGAGAC 
               
               
                   
                   
                 GGTGTCAGGAAGGTTCAGACCATCTTGGAAAA 
               
               
                   
                   
                 ACTTGAACAGAAAGCCATTGATGTCCCAGGTC 
               
               
                   
                   
                 AAGTCCAGGTCTATGAACTCCAGCCCAGCAAC 
               
               
                   
                   
                 CTTGAAGCAGATCAGCCACTGCAGGCAATCAT 
               
               
                   
                   
                 GGAGATGGGTGCCGTGGCAGCAGACAAGGGCA 
               
               
                   
                   
                 AGAAAAATGCTGGAAATGCAGAAGATCCCCAC 
               
               
                   
                   
                 ACAGAAACCCAGCAGCCAGAAGCCACAGCAGC 
               
               
                   
                   
                 AGCGACTTCAAACCCCAGCAGCATGACAGACA 
               
               
                   
                   
                 CCCCTGGTAACCCAGCAGCACCGTAG (SEQ ID 
               
               
                   
                   
                 NO: 205) 
               
               
                   
               
               
                 Human 
                 MDIAIHHPWIRRPFFPFHSPSRLFD 
                 ATGGACATCGCCATCCACCACCCCTGGATCCGC 
               
               
                 CRYAB 
                 QFFGEHLLESDLFPTSTSLSPFYLR 
                 CGCCCCTTCTTTCCTTTCCACTCCCCCAGCCGCC 
               
               
                   
                 PPSFLRAPSWFDTGLSEMRLEKDR 
                 TCTTTGACCAGTTCTTCGGAGAGCACCTGTTGG 
               
               
                   
                 FSVNLDVKHFSPEELKVKVLGDVI 
                 AGTCTGATCTTTTCCCGACGTCTACTTCCCTGA 
               
               
                   
                 EVHGKHEERQDEHGFISREFHRK 
                 GTCCCTTCTACCTTCGGCCACCCTCCTTCCTGCG 
               
               
                   
                 YRIPADVDPLTITSSLSSDGVLTVN 
                 GGCACCCAGCTGGTTTGACACTGGACTCTCAGA 
               
               
                   
                 GPRKQVSGPERTIPITREEKPAVT 
                 GATGCGCCTGGAGAAGGACAGGTTCTCTGTCA 
               
               
                   
                 AAPKK (SEQ ID NO: 206) 
                 ACCTGGATGTGAAGCACTTCTCCCCAGAGGAA 
               
               
                   
                   
                 CTCAAAGTTAAGGTGTTGGGAGATGTGATTGA 
               
               
                   
                   
                 GGTGCATGGAAAACATGAAGAGCGCCAGGATG 
               
               
                   
                   
                 AACATGGTTTCATCTCCAGGGAGTTCCACAGGA 
               
               
                   
                   
                 AATACCGGATCCCAGCTGATGTAGACCCTCTCA 
               
               
                   
                   
                 CCATTACTTCATCCCTGTCATCTGATGGGGTCC 
               
               
                   
                   
                 TCACTGTGAATGGACCAAGGAAACAGGTCTCT 
               
               
                   
                   
                 GGCCCTGAGCGCACCATTCCCATCACCCGTGAA 
               
               
                   
                   
                 GAGAAGCCTGCTGTCACCGCAGCCCCCAAGAA 
               
               
                   
                   
                 ATAG (SEQ ID NO: 205) 
               
               
                   
               
               
                 Human 
                 METPSQRRATRSGAQASSTPLSPT 
                 ATGGAGACCCCGTCCCAGCGGCGCGCCACCCG 
               
               
                 LMNA 
                 RITRLQEKEDLQELNDRLAVYIDR 
                 CAGCGGGGCGCAGGCCAGCTCCACTCCGCTGT 
               
               
                 LaminA 
                 VRSLETENAGLRLRITESEEVVSR 
                 CGCCCACCCGCATCACCCGGCTGCAGGAGAAG 
               
               
                   
                 EVSGIKAAYEAELGDARKTLDSV 
                 GAGGACCTGCAGGAGCTCAATGATCGCTTGGC 
               
               
                   
                 AKERARLQLELSKVREEFKELKA 
                 GGTCTACATCGACCGTGTGCGCTCGCTGGAAAC 
               
               
                   
                 RNTKKEGDLIAAQARLKDLEALL 
                 GGAGAACGCAGGGCTGCGCCTTCGCATCACCG 
               
               
                   
                 NSKEAALSTALSEKRTLEGELHDL 
                 AGTCTGAAGAGGTGGTCAGCCGCGAGGTGTCC 
               
               
                   
                 RGQVAKLEAALGEAKKQLQDEM 
                 GGCATCAAGGCCGCCTACGAGGCCGAGCTCGG 
               
               
                   
                 LRRVDAENRLQTMKEELDFQKNI 
                 GGATGCCCGCAAGACCCTTGACTCAGTAGCCA 
               
               
                   
                 YSEELRETKRRHETRLVEIDNGKQ 
                 AGGAGCGCGCCCGCCTGCAGCTGGAGCTGAGC 
               
               
                   
                 REFESRLADALQELRAQHEDQVE 
                 AAAGTGCGTGAGGAGTTTAAGGAGCTGAA 
               
               
                   
                 QYKKELEKTYSAKLDNARQSAER 
                 AGCGCGCAATACCAAGAAGGAGGGTGACCTGA 
               
               
                   
                 NSNLVGAAHEELQQSRIRIDSLSA 
                 TAGCTGCTCAGGCTCGGCTGAAGGACCTGGAG 
               
               
                   
                 QLSQLQKQLAAKEAKLRDLEDSL 
                 GCTCTGCTGAACTCCAAGGAGGCCGCACTGAG 
               
               
                   
                 ARERDTSRRLLAEKEREMAEMRA 
                 CACTGCTCTCAGTGAGAAGCGCACGCTGGAGG 
               
               
                   
                 RMQQQLDEYQELLDIKLALDMEI 
                 GCGAGCTGCATGATCTGCGGGGCCAGGTGGCC 
               
               
                   
                 HAYRKLLEGEEERLRLSPSPTSQR 
                 AAGCTTGAGGCAGCCCTAGGTGAGGCCAAGAA 
               
               
                   
                 SRGRASSHSSQTQGGQSVTKKRK 
                 GCAACTTCAGGATGAGATGCTGCGGCGGGTGG 
               
               
                   
                 LESTESRSSFSQHARTSGRVAVEE 
                 ATGCTGAGAACAGGCTGCAGACCATGAAGGAG 
               
               
                   
                 VDEEGKFVRLRNKSNEDQSMGN 
                 GAACTGGACTTCCAGAAGAACATCTACAGTGA 
               
               
                   
                 WQIKRQNGDDPLLTYRFPPKFTL 
                 GGAGCTGCGTGAGACCAAGCGCCGTCATGAGA 
               
               
                   
                 KAGQVVTIWAAQAGATHSPPTDL 
                 CCCGACTGGTGGAGATTGACAATGGGAAGCAG 
               
               
                   
                 VWKAQNTWGCGNSLRTALINST 
                 CGTGAGTTTGAGAGCCGGCTGGCGGATGCGCT 
               
               
                   
                 GEEVAMRKLVRSVTVVEDDEDE 
                 GCAGGAACTGCGGGCCCAGCATGAGGACCAGG 
               
               
                   
                 DGDDLLHHHHGSHCSSSGDPAEY 
                 TGGAGCAGTATAAGAAGGAGCTGGAGAAGACT 
               
               
                   
                 NLRSRTVLCGTCGQPADKASASG 
                 TATTCTGCCAAGCTGGACAATGCCAGGCAGTCT 
               
               
                   
                 SGAQVQGPISSQSSASSVTVTRSY 
                 GCTGAGAGGAACAGCAACCTGGTGGGGGCTGC 
               
               
                   
                 RSVGGSGGGSFGDNLVTRSYLLG 
                 CCACGAGGAGCTGCAGCAGTCGCGCATCCGCA 
               
               
                   
                 NSSPRTQSPQNCSIM (SEQ ID NO: 
                 TCGACAGCCTCTCTGCCCAGCTCAGCCAGCTCC 
               
               
                   
                 208) 
                 AGAAGCAGCTGGCAGCCAAGGAGGCGAAGCTT 
               
               
                   
                   
                 CGAGACCTGGAGGACTCACTGGCCCGTGAGCG 
               
               
                   
                   
                 GGACACCAGCCGGCGGCTGCTGGCGGAAAAGG 
               
               
                   
                   
                 AGCGGGAGATGGCCGAGATGCGGGCAAGGATG 
               
               
                   
                   
                 CAGCAGCAGCTGGACGAGTACCAGGAGCTTCT 
               
               
                   
                   
                 GGACATCAAGCT 
               
               
                   
                   
                 GGCCCTGGACATGGAGATCCACGCCTACCGCA 
               
               
                   
                   
                 AGCTCTTGGAGGGCGAGGAGGAGAGGCTACGC 
               
               
                   
                   
                 CTGTCCCCCAGCCCTACCTCGCAGCGCAGCCGT 
               
               
                   
                   
                 GGCCGTGCTTCCTCTCACTCATCCCAGACACAG 
               
               
                   
                   
                 GGTGGGGGCAGCGTCACCAAAAAGCGCAAACT 
               
               
                   
                   
                 GOAGTCCACTGAGAGCCGCAGCAGCTTCTCAC 
               
               
                   
                   
                 AGCACGCACGCACTAGCGGGCGCGTGGCCGTG 
               
               
                   
                   
                 GAGGAGGTGGATGAGGAGGGCAAGTTTGTCCG 
               
               
                   
                   
                 GCTGCGCAACAAGTCCAATGAGGACCAGTCCA 
               
               
                   
                   
                 TGGGCAATTGGCAGATCAAGCGCCAGAATGGA 
               
               
                   
                   
                 GATGATCCCTTGCTGACTTACCGGTTCC 
               
               
                   
                   
                 CACCAAAGTTCACCCTGAAGGCTGGGCAGGTG 
               
               
                   
                   
                 GTGACGATCTGGGCTGCAGGAGCTGGGGCCAC 
               
               
                   
                   
                 CCACAGCCCCCCTACCGACCTGGTGTGGAAGG 
               
               
                   
                   
                 CACAGAACACCTGGGGCTGCGGGAACAGCCTG 
               
               
                   
                   
                 CGTACGGCTCTCATCAACTCCACTGGGGAAGA 
               
               
                   
                   
                 AGTGGCCATGCGCAAGCTGGTGCGCTCAGTGA 
               
               
                   
                   
                 CTGTGGTTGAGGACGACGAGGATGAGGATGGA 
               
               
                   
                   
                 GATGACCTGCTCCATCACCACCACGGCTCCCAC 
               
               
                   
                   
                 TGCAGCAGCTCGGGGGACCCCGCTGAGTACAA 
               
               
                   
                   
                 CCTGCGCTCGCGCACCGTGCTGTGCGGGACCTG 
               
               
                   
                   
                 CGGGCAGCCTGCCGACAAGGCATCTGCCAGCG 
               
               
                   
                   
                 GCTCAGGAGCCCAGGTGGGCGGACCCATCTCC 
               
               
                   
                   
                 TCTGGCTCTTCTGCCTCCAGTGTCACGGTCACT 
               
               
                   
                   
                 CGCAGCTACCGCAGTGTGGGGGGCAGTGGGGG 
               
               
                   
                   
                 TGGCAGCTTCGGGGACAATCTGGTCACCCGCTC 
               
               
                   
                   
                 CTACCTCCTGGGCAACTCCAGCCCCCGAACCCA 
               
               
                   
                   
                 GAGCCCCCAGAACTGCAGCATCATGTAA(SEQ 
               
               
                   
                   
                 ID NO: 207) 
               
               
                   
               
               
                 Human 
                 METPSQRRATRSGAQASSTPLSPT 
                 ATGGAGACCCCGTCCCAGCGGCGCGCCACCCG 
               
               
                 LMNA 
                 RIIRLQEKEDIQELNDRLAVYIDR 
                 CAGCGGGGCGCAGGCCAGCTCCACTCCGCTGT 
               
               
                 LaminC 
                 VRSLETENAGLRLRITESEEVVSR 
                 CGCCCACCCGCATCACCCGGCTGCAGGAGAAG 
               
               
                   
                 EVSGIKAAYEAELGDARKTLDSV 
                 GAGGACCTGCAGGAGCTCAATGATCGCTTGGC 
               
               
                   
                 AKERARLQLELSKVREEFKELKA 
                 GGTCTACATCGACCGTGTGCGCTCGCTGGAAAC 
               
               
                   
                 RNTKKEGDLIAAQARLKDLEALL 
                 GGAGAACGCAGGGCTGCGCCTTCGCATCACCG 
               
               
                   
                 NSKEAALSTALSEKRTLEGELHDL 
                 AGTCTGAAGAGGTGGTCAGCCGCGAGGTGTCC 
               
               
                   
                 RGQVAKLEAALGEAKKQLQDEM 
                 GGCATCAAGGCCGCCTACGAGGCCGAGCTCGG 
               
               
                   
                 LRRVDAENRLQTMKEELDFQKNI 
                 GGATGCCCGCAAGACCCTTGACTCAGTAGCCA 
               
               
                   
                 YSEELRETKRRHETRLVEIDNGKQ 
                 AGGAGCGCGCCCGCCTGCAGCTGGAGCTGAGC 
               
               
                   
                 REFESRLADALQELRAQHEDQVE 
                 AAAGTGCGTGAGGAGTTTAAGGAGCTGAA 
               
               
                   
                 QYKKELEKTYSAKIDNARQSAER 
                 AGCGCGCAATACCAAGAAGGAGGGTGACCTGA 
               
               
                   
                 NSNLVGAAHEELQQSRIRIDSLSA 
                 TAGCTGCTCAGGCTCGGCTGAAGGACCTGGAG 
               
               
                   
                 QLSQLQKQLAAKEAKLRDLEDSL 
                 GCTCTGCTGAACTCCAAGGAGGCCGCACTGAG 
               
               
                   
                 ARERDTSRRLLAEKEREMAEMRA 
                 CACTGCTCTCAGTGAGAAGCGCACGCTGGAGG 
               
               
                   
                 RMQQQLDEYQELLDIKLALDMEI 
                 GCGAGCTGCATGATCTGCGGGGCCAGGTGGCC 
               
               
                   
                 HAYRKLLEGEEERLRLSPSPTSQR 
                 AAGCTTGAGGCAGCCCTAGGTGAGGCCAAGAA 
               
               
                   
                 SRGRASSHSSQTQGGGSVTKKRK 
                 GCAACTTCAGGATGAGATGCTGCGGCGGGTGG 
               
               
                   
                 LESTESRSSFSQHARTSGRVAVEE 
                 ATGCTGAGAACAGGCTGCAGACCATGAAGGAG 
               
               
                   
                 VDEEGKFVRLRNKSNEDQSMGN 
                 GAACTGGACTTCCAGAAGAACATCTACAGTGA 
               
               
                   
                 WQIKRQNGDDPLLTYRFPPKFTL 
                 GGAGCTGCGTGAGACCAAGCGCCGTCATGAGA 
               
               
                   
                 KAGQVVTIWAAGAGATHSPPTDL 
                 CCCGACTGGTGGAGATTGACAATGGGAAGCAG 
               
               
                   
                 VWKAQNTWGCGNSLRTALINST 
                 CGTGAGTTTGAGAGCCGGCTGGCGGATGCGCT 
               
               
                   
                 GEEVAMRKLVRSVTVVEDDEDE 
                 GCAGGAACTGCGGGCCCAGCATGAGGACCAGG 
               
               
                   
                 DGDDLLHHHHVSGSRR (SEQ ID 
                 TGGAGCAGTATAAGAAGGAGCTGGAGAAGACT 
               
               
                   
                 NO: 210) 
                 TATTCTGCCAAGCTGGACAATGCCAGGCAGTCT 
               
               
                   
                   
                 GCTGAGAGGAACAGCAACCTGGTGGGGGCTGC 
               
               
                   
                   
                 CCACGAGGAGCTGCAGCAGTCGCGCATCCGCA 
               
               
                   
                   
                 TCGACAGCCTCTCTGCCCAGCTCAGCCAGCTCC 
               
               
                   
                   
                 AGAAGCAGCTGGCAGCCAAGGAGGCGAAGCTT 
               
               
                   
                   
                 CGAGACCTGGAGGACTCACTGGCCCGTGAGCG 
               
               
                   
                   
                 GGACACCAGCCGGCGGCTGCTGGCGGAAAAGG 
               
               
                   
                   
                 AGCGGGAGATGGCCGAGATGCGGGCAAGGATG 
               
               
                   
                   
                 CAGCAGCAGCTGGACGAGTACCAGGAGCTTCT 
               
               
                   
                   
                 GGACATCAAGCTGGCCCTGGACATGGAGATCC 
               
               
                   
                   
                 ACGCCTACCGCAAGCTCTTGGAGGGCGAGGAG 
               
               
                   
                   
                 GAGAGGCTACGCCTGTCCCCCAGCCCTACCTCG 
               
               
                   
                   
                 CAGCGCAGCCGTGGCCGTGCTTCCTCTCACTCA 
               
               
                   
                   
                 TCCCAGACACAGGGTGGGGGCAGCGTCACCAA 
               
               
                   
                   
                 AAAGCGCAAACTGGAGTCCACTGAGAGCCGCA 
               
               
                   
                   
                 GCAGCTTCTCACAGCACGCACGCACTAGCGGG 
               
               
                   
                   
                 CGCGTGGCCGTGGAGGAGGTGGATGAGGAGGG 
               
               
                   
                   
                 CAAGTTTGTCCGGCTGCGCAACAAGTCCAATGA 
               
               
                   
                   
                 GGACCAGTCCATGGGCAATTGGCAGATCAAGC 
               
               
                   
                   
                 GCCAGAATGGAGATGATCCCTTGCTGACTTACC 
               
               
                   
                   
                 GGTTCC 
               
               
                   
                   
                 CACCAAAGTTCACCCTGAAGGCTGGGCAGGTG 
               
               
                   
                   
                 GTGACGATCTGGGCTGCAGGAGCTGGGGCCAC 
               
               
                   
                   
                 CCACAGCCCCCCTACCGACCTGGTGTGGAAGG 
               
               
                   
                   
                 CACAGAACACCTGGGGCTGCGGGAACAGCCTG 
               
               
                   
                   
                 CGTACGGCTCTCATCAACTCCACTGGGGAAGA 
               
               
                   
                   
                 AGTGGCCATGCGCAAGCTGGTGCGCTCAGTGA 
               
               
                   
                   
                 CTGTGGTTGAGGACGACGAGGATGAGGATGGA 
               
               
                   
                   
                 GATGACCTGCTCCATCACCACCACGTGAGTGGT 
               
               
                   
                   
                 AGCCGCCGCTGA (SEQ ID NO: 209) 
               
               
                   
               
               
                 Human 
                 MADGSSDAAREPRPAPAPIRRRSS 
                 ATGGCGGATGGGAGCAGCGATGCGGCTAGGGA 
               
               
                 TNNI3 
                 NYRAYATEPHAKKKSKISASRKL 
                 ACCTCGCCCTGCACCAGCCCCAATCAGACGCCG 
               
               
                   
                 QLKTLLLQIAKQELEREAEERRGE 
                 CTCCTCCAACTACCGCGCTTATGCCACGGAGCC 
               
               
                   
                 KGRALSTRCQPLELAGLGFAELQ 
                 GCACGCCAAGAAAAAATCTAAGATCTCCGCCT 
               
               
                   
                 DLCRQLHARVDKVDEERYDIEAK 
                 CGAGAAAATTGCAGCTGAAGACTCTGCTGCTG 
               
               
                   
                 VTKNITEIADLTQKIFDLRGKFKR 
                 CAGATTGCAAAGCAAGAGCTGGAGCGAGAGGC 
               
               
                   
                 PTLRRVRISADAMMQALLGARAK 
                 GGAGGAGCGGCGCGGAGAGAAGGGGCGCGCT 
               
               
                   
                 ESLDLRAHLKQVKKEDTEKENRE 
                 CTGAGCACCCGCTGCCAGCCGCTGGAGTTGGCC 
               
               
                   
                 VGDWRKNIDALSGMEGRKKKFE 
                 GGGCTGGGCTTCGCGGAGCTGCAGGACTTGTG 
               
               
                   
                 S (SEQ ID NO: 212) 
                 CCGACAGCTCCACGCCCGTGTGGACAAGGTGG 
               
               
                   
                   
                 ATGAAGAGAGATACGACATAGAGGCAAAAGTC 
               
               
                   
                   
                 ACCAAGAACATCACGGAGATTGCAGATCTGAC 
               
               
                   
                   
                 TCAGAAGATCTTTGACCTTCGAGGCAAGTTTAA 
               
               
                   
                   
                 GCGGCCCACCCTGCGGAGAGTGAGGATCTCTG 
               
               
                   
                   
                 CAGATGCCATGATGCAGGCGCTGCTGGGGGCC 
               
               
                   
                   
                 CGGGCTAAGGAGTCCCTGGACCTGCGGGCCCA 
               
               
                   
                   
                 CCTCAAGCAGGTGAAGAAGGAGGACACCGAGA 
               
               
                   
                   
                 AGGAAAACCGGGAGGTGGGAGACTGGCGCAA 
               
               
                   
                   
                 GAACATCGATGCACTGAGTGGAATGGAGGGCC 
               
               
                   
                   
                 GCAAGAAAAAGTTTGAGAGCTGA (SEQ ID NO: 
               
               
                   
                   
                 211) 
               
               
                   
               
               
                 Human 
                 MVCFRLFPVPGSGLVLVCLVLGA 
                 ATGGTGTGCTTCCGCCTCTTCCCGGTTCCGGGC 
               
               
                 LAMP2a 
                 VRSYALELNLTDSENATCLYAKW 
                 TCAGGGCTCGTTCTGGTCTGCCTAGTCCTGGGA 
               
               
                   
                 QMNFTVRYETTNKTYKTVTISDH 
                 GCTGTGCGGTCTTATGCATTGGAACTTAATTTG 
               
               
                   
                 GTVTYNGSICGDDQNGPKIAVQP 
                 ACAGATTCAGAAAATGCCACTTGCCTTTATGCA 
               
               
                   
                 GPGFSWIANFTKAASTYSIDSVSF 
                 AAATGGCAGATGAATTTCACAGTACGCTATGA 
               
               
                   
                 SYNTGDNTTFPDAEDKGILTVDEL 
                 AACTACAAATAAAACTTATAAAACTGTAACCA 
               
               
                   
                 LAIRIPLNDLFRCNSLSTLEKNDV 
                 TTTCAGACCATGGCACTGTGACATATAATGGAA 
               
               
                   
                 VQHYWDVLVQAFVQNGTVSTNE 
                 GCATTTGTGGGGATGATCAGAATGGTCCCAAA 
               
               
                   
                 FLCDKDKTSTVAPTIHTTVPSPTT 
                 ATAGCAGTGCAGTTCGGACCTGGCTTTTCCTGG 
               
               
                   
                 TPTPKEKPEAGTYSVNNGNDTCL 
                 ATTGCGAATTTTACCAAGGCAGCATCTACTTAT 
               
               
                   
                 LATMGLQLNITQDKVASVININPN 
                 TCAATTGACAGCGTCTCATTTTCCTACAACACT 
               
               
                   
                 TTHSTGSCRSHTALLRLNSSTIKY 
                 GGTGATAACACAACATTTCCTGATGCTGAAGAT 
               
               
                   
                 LDFVFAVKNENRFYLKEVNISMY 
                 AAAGGAATTCTTACTGTTGATGAACTTTTGGCC 
               
               
                   
                 LVNGSVFSIANNNLSYWDAPLGS 
                 ATCAGAATTCCATTGAATGACCTTTTTAGATGC 
               
               
                   
                 SYMCNKEQTVSVSGAFQINTFDL 
                 AATAGTTTATCAACTTTGGAAAAGAATGATGTT 
               
               
                   
                 RVQPFNVTQGKYSTAQDCSADD 
                 GTCCAACACTACTGGGATGTTCTTGTACAAGCT 
               
               
                   
                 DNFLVPIAVGAALAGVLILVLLAY 
                 TTTGTCCAAAATGGCACAGTGAGCACAAATGA 
               
               
                   
                 FIGLKHHHAGYEQF (SEQ ID NO: 
                 GTTCCTGTGTGATAAAGACAAAACTTCAACAGT 
               
               
                   
                 214) 
                 GGCACCCACCATACACACCACTGTGCCATCTCC 
               
               
                   
                   
                 TACTACAACACCTACTCCAAAGGAAAAACCAG 
               
               
                   
                   
                 AAGCTGGAACCTATTCAGTTAATAATGGCAATG 
               
               
                   
                   
                 ATACTTGTCTGCTGGCTACCATGGGGCTGCAGC 
               
               
                   
                   
                 TGAACATCACTCAGGATAAGGTTGCTTCAGTTA 
               
               
                   
                   
                 TTAACATCAACCCCAATACAACTCACTCCACAG 
               
               
                   
                   
                 GCAGCTGCCGTTCTCACACTGCTCTACTTAGAC 
               
               
                   
                   
                 TCAATAGCAGCACCATTAAGTATCTAGACTTTG 
               
               
                   
                   
                 TCTTTGCTGTGAAAAATGAAAACCGATTTTATC 
               
               
                   
                   
                 TGAAGGAAGTGAACATCAGCATGTATTTGGTTA 
               
               
                   
                   
                 ATGGCTCCGTTTTCAGCATTGCAAATAACAATC 
               
               
                   
                   
                 TCAGCTACTGGGATGCCCCCCTGGGAAGTTCTT 
               
               
                   
                   
                 ATATGTGCAACAAAGAGCAGACTGTTTCAGTGT 
               
               
                   
                   
                 CTGGAGCATTTCAGATAAATACCTTTGATCTAA 
               
               
                   
                   
                 GGGTTCAGCCTTTCAATGTGACACAAGGAAAG 
               
               
                   
                   
                 TATTCTACAGCTCAAGACTGCAGTGCAGATGAC 
               
               
                   
                   
                 GACAACTTCCTTGTGCCCATAGCGGTGGGAGCT 
               
               
                   
                   
                 GCCTTGGCAGGAGTACTTATTCTAGTGTTGCTG 
               
               
                   
                   
                 GCTTATTTTATTGGTCTCAAGCACCATCATGCT 
               
               
                   
                   
                 GGATATGAGCAATTTTAG (SEQ ID NO: 213) 
               
               
                   
               
               
                 Human 
                 MVCFRLFPVPGSGLVLVCLVLGA 
                 ATGGTGTGCTTCCGCCTCTTCCCGGTTCCGGGC 
               
               
                 LAMP2b 
                 VRSYALELNLTDSENATCLYAKW 
                 TCAGGGCTCGTTCTGGTCTGCCTAGTCCTGGGA 
               
               
                   
                 QMNFTVRYETTNKTYKTVTISDH 
                 GCTGTGCGGTCTTATGCATTGGAACTTAATTTG 
               
               
                   
                 GTVTYNGSICGDDQNGPKIAVQF 
                 ACAGATTCAGAAAATGCCACTTGCCTTTATGCA 
               
               
                   
                 GPGFSWIANFTKAASTYSIDSVSF 
                 AAATGGCAGATGAATTTCACAGTACGCTATGA 
               
               
                   
                 SYNTGDNTTFPDAEDKGILTVDEL 
                 AACTACAAATAAAACTTATAAAACTGTAACCA 
               
               
                   
                 LAIRIPLNDLFRCNSLSTLEKNDV 
                 TTTCAGACCATGGCACTGTGACATATAATGGAA 
               
               
                   
                 VQHYWDVLVQAFVQNGTVSTNE 
                 GCATTTGTGGGGATGATCAGAATGGTCCCAAA 
               
               
                   
                 FLCDKDKTSTVAPTIHTTVPSPTT 
                 ATAGCAGTGCAGTTCGGACCTGGCTTTTCCTGG 
               
               
                   
                 TPTPKEKPEAGTYSVNNGNDTCL 
                 ATTGCGAATTTTACCAAGGCAGCATCTACTTAT 
               
               
                   
                 LATMGLQLNITQDKVASVININPN 
                 TCAATTGACAGCGTCTCATTTTCCTACAACACT 
               
               
                   
                 TTHSTGSCRSHTALLRLNSSTIKY 
                 GGTGATAACACAACATTTCCTGATGCTGAAGAT 
               
               
                   
                 LDFVFAVKNENRFYLKEVNISMY 
                 AAAGGAATTCTTACTGTTGATGAACTTTTGGCC 
               
               
                   
                 LVNGSVFSIANNNLSYWDAPLGS 
                 ATCAGAATTCCATTGAATGACCTTTTTAGATGC 
               
               
                   
                 SYMCNKEQTVSVSGAFQINTFDL 
                 AATAGTTTATCAACTTTGGAAAAGAATGATGTT 
               
               
                   
                 RVQPFNVTQGKYSTAQECSLDDD 
                 GTCCAACACTACTGGGATGTTCTTGTACAAGCT 
               
               
                   
                 TILIPIIVGAGLSGLIIVIVIAYVIGR 
                 TTTGTCCAAAATGGCACAGTGAGCACAAATGA 
               
               
                   
                 RKSYAGYQTL (SEQ ID NO: 216) 
                 GTTCCTGTGTGATAAAGACAAAACTTCAACAGT 
               
               
                   
                   
                 GGCACCCACCATACACACCACTGTGCCATCTCC 
               
               
                   
                   
                 TACTACAACACCTACTCCAAAGGAAAAACCAG 
               
               
                   
                   
                 AAGCTGGAACCTATTCAGTTAATAATGGCAATG 
               
               
                   
                   
                 ATACTTGTCTGCTGGCTACCATGGGGCTGCAGC 
               
               
                   
                   
                 TGAACATCACTCAGGATAAGGTTGCTTCAGTTA 
               
               
                   
                   
                 TTAACATCAACCCCAATACAACTCACTCCACAG 
               
               
                   
                   
                 GCAGCTGCCGTTCTCACACTGCTCTACTTAGAC 
               
               
                   
                   
                 TCAATAGCAGCACCATTAAGTATCTAGACTTTG 
               
               
                   
                   
                 TCTTTGCTGTGAAAAATGAAAACCGATTTTATC 
               
               
                   
                   
                 TGAAGGAAGTGAACATCAGCATGTATTTGGTTA 
               
               
                   
                   
                 ATGGCTCCGTTTTCACCATTGCAAATAACAATC 
               
               
                   
                   
                 TCAGCTACTGGGATGCCCCCCTGGGAAGTTCTT 
               
               
                   
                   
                 ATATGTGCAACAAAGAGCAGACTGTTTCAGTGT 
               
               
                   
                   
                 CTGGAGCATTTCAGATAAATACCTTTGATCTAA 
               
               
                   
                   
                 GGGTTCAGCCTTTCAATGTGACACAAGGAAAG 
               
               
                   
                   
                 TATTCTACAGCCCAAGAGTGTTCGCTGGATGAT 
               
               
                   
                   
                 GACACCATTCTAATCCCAATTATAGTTGGTGCT 
               
               
                   
                   
                 GGTCTTTCAGGCTTGATTATCGTTATAGTGATT 
               
               
                   
                   
                 GCTTACGTAATTGGCAGA 
               
               
                   
                   
                 AGAAAAAGTTATGCTGGATATCAGACTCTGTA 
               
               
                   
                   
                 A (SEQ ID NO: 215) 
               
               
                   
               
               
                 Human 
                 MVCFRLFPVPGSGLVLVCLVLGA 
                 ATGGTGTGCTTCCGCCTCTTCCCGGTTCCGGGC 
               
               
                 LAMP2 
                 VRSYALELNLTDSENATCLYAKW 
                 TCAGGGCTCGTTCTGGTCTGCCTAGTCCTGGGA 
               
               
                   
                 QMNFTVRYETTNKTYKTVTISDH 
                 GCTGTGCGGTCTTATGCATTGGAACTTAATTTG 
               
               
                   
                 GTVTYNGSICGDDQNGPKIAVQF 
                 ACAGATTCAGAAAATGCCACTTGCCTTTATGCA 
               
               
                   
                 GPGFSWIANFTKAASTYSIDSVSF 
                 AAATGGCAGATGAATTTCACAGTACGCTATGA 
               
               
                   
                 SYNTGDNTTFPDAEDKGIITVDEL 
                 AACTACAAATAAAACTTATAAAACTGTAACCA 
               
               
                   
                 LAIRIPLNDLFRCNSLSTLEKNDV 
                 TTTCAGACCATGGCACTGTGACATATAATGGAA 
               
               
                   
                 VQHYWDVLVQAFVQNGTVSTNE 
                 GCATTTGTGGGGATGATCAGAATGGTCCCAAA 
               
               
                   
                 FLCDKDKTSTVAPTIHTTVPSPTT 
                 ATAGCAGTGCAGTTCGGACCTGGCTTTTCCTGG 
               
               
                   
                 TPTPKEKPEAGTYSVNNGNDTCL 
                 ATTGCGAATTTTACCAAGGCAGCATCTACTTAT 
               
               
                   
                 LATMGLQLNITQDKVASVININPN 
                 TCAATTGACAGCGTCTCATTTTCCTACAACACT 
               
               
                   
                 TTHSTGSCRSHTALLRLNSSTIKY 
                 GGTGATAACACAACATTTCCTGATGCTGAAGAT 
               
               
                   
                 LDFVFAVKNENRFYLKEVNISMY 
                 AAAGGAATTCTTACTGTTGATGAACTTTTGGCC 
               
               
                   
                 LVNGSVFSIANNNLSYWDAPLGS 
                 ATCAGAATTCCATTGAATGACCTTTTTAGATGC 
               
               
                   
                 SYMCNKEQTVSVSGAFQINTFDL 
                 AATAGTTTATCAACTTTGGAAAAGAATGATGTT 
               
               
                   
                 RVQPFNVTQGKYSTAEECSADSD 
                 GTCCAACACTACTGGGATGTTCTTGTACAAGCT 
               
               
                   
                 LNFLIPVAVGVALGFLIIVVFISYM 
                 TTTGTCCAAAATGGCACAGTGAGCACAAATGA 
               
               
                   
                 IGRRKSRTGYQSV (SEQ ID NO: 
                 GTTCCTGTGTGATAAAGACAAAACTTCAACAGT 
               
               
                   
                 218) 
                 GGCACCCACCATACACACCACTGTGCCATCTCC 
               
               
                   
                   
                 TACTACAACACCTACTCCAAAGGAAAAACCAG 
               
               
                   
                   
                 AAGCTGGAACCTATTCAGTTAATAATGGCAATG 
               
               
                   
                   
                 ATACTTGTCTGCTGGCTACCATGGGGCTGCAGC 
               
               
                   
                   
                 TGAACATCACTCAGGATAAGGTTGCTTCAGTTA 
               
               
                   
                   
                 TTAACATCAACCCCAATACAACTCACTCCACAG 
               
               
                   
                   
                 GCAGCTGCCGTTCTCACACTGCTCTACTTAGAC 
               
               
                   
                   
                 TCAATAGCAGCACCATTAAGTATCTAGACTTTG 
               
               
                   
                   
                 TCTTTGCTGTGAAAAATGAAAACCGATTTTATC 
               
               
                   
                   
                 TGAAGGAAGTGAACATCAGCATGTATTTGGTTA 
               
               
                   
                   
                 ATGGCTCCGTTTTCAGCATTGCAAATAACAATC 
               
               
                   
                   
                 TCAGCTACTGGGATGCCCCCCTGGGAAGTTCTT 
               
               
                   
                   
                 ATATGTGCAACAAAGAGCAGACTGTTTCAGTGT 
               
               
                   
                   
                 CTGGAGCATTTCAGATAAATACCTTTGATCTAA 
               
               
                   
                   
                 GGGTTCAGCCTTTCAATGTGACACAAGGAAAG 
               
               
                   
                   
                 TATTCTACAGCTGAAGAATGTTCTGCTGACTCT 
               
               
                   
                   
                 GACCTCAACTTTCTTATTCCTGTTGCAGTGGGT 
               
               
                   
                   
                 GTGGCCTTGGGCTTCCTTATAATTGTTGTCTTTA 
               
               
                   
                   
                 TCTCTTATATGATTGGAAGAAGGAAAAGTCGTA 
               
               
                   
                   
                 CTGGTTATCAGTCTGTGTAA (SEQ ID NO: 217) 
               
               
                   
               
               
                 Human 
                 MSCNGGSHPRINTLGRMIRAESGP 
                 ATGAGCTGCAACGGAGGCTCCCACCCGCGGAT 
               
               
                 DSP DPI 
                 DLRYEVTSGGGGTSRMYYSRRG 
                 CAACACTCTGGGCCGCATGATCCGCGCCGAGTC 
               
               
                   
                 VITDQNSDGYCQTGTMSRHQNQ 
                 TGGCCCGGACCTGCGCTACGAGGTGACCAGCG 
               
               
                   
                 NTIQELLQNCSDCLMRAELIVQPE 
                 GCGGCGGGGGCACCAGCAGGATGTACTATTCT 
               
               
                   
                 LKYGDGIQLTRSRELDECFAQAN 
                 CGGCGCGGCGTGATCACCGACCAGAACTCGGA 
               
               
                   
                 DQMEILDSLIREMRQMGQPCDAY 
                 CGGCTACTGTCAAACCGGCACGATGTCCAGGC 
               
               
                   
                 QKRLLQLQEQMRAIYKAISVPRV 
                 ACCAGAACCAGAACACCATCCAGGAGCTGCTG 
               
               
                   
                 RRASSKGGGGYTCQSGSGWDEFT 
                 CAGAACTGCTCCGACTGCTTGATGCGAGCAGA 
               
               
                   
                 KHVTSECLGWMRQQRAEMDMV 
                 GCTCATCGTGCAGCCTGAATTGAAGTATGGAG 
               
               
                   
                 AWGVDLASVIQHINSHRGIHNSI 
                 ATGGAATACAACTGACTCGGAGTCGAGAATTG 
               
               
                   
                 GDYRWQLDKIKADLREKSAIYQL 
                 GATGAGTGTTTTGCCCAGGCCAATGACCA 
               
               
                   
                 EEEYENLLKASFERMDHLRQLQN 
                 AATGGAAATCCTCGACAGCTTGATCAGAGAGA 
               
               
                   
                 IIQATSREIMWINDCEEEELLYDW 
                 TGCGGCAGATGGGCCAGCCCTGTGATGCTTACC 
               
               
                   
                 SDKNTNIAQKQEAFSIRMSQLEVK 
                 AGAAAAGGCTTCTTCAGCTCCAAGAGCAAATG 
               
               
                   
                 EKELNKIKQESDQLVLNQHPASD 
                 CGAGCCCTTTATAAAGCCATCAGTGTCCCTCGA 
               
               
                   
                 KIEAYMDTLQTQWSW 
                 GTCCGCAGGGCCAGCTCCAAGGGTGGTGGAGG 
               
               
                   
                 ILQITKCIDVHLKENAAYFQFFEE 
                 CTACACTTGTCAGAGTGGCTCTGGCTGGGATGA 
               
               
                   
                 AQSTEAYLKGLQDSIRKKYPCDK 
                 GTTCACCAAACATGTCACCAGTGAATGTTTGGG 
               
               
                   
                 NMPLQHLLEQIKELEKEREKILEY 
                 GTGGATGAGGCAGCAAAGGGCGGAGATGGACA 
               
               
                   
                 KRQVQNLVNKSKKIVQLKPRNPD 
                 TGGTGGCCTGGGGTGTGGACCTGGCCTCAGTGG 
               
               
                   
                 YRSNKPIILRALCDYKQDQKIVHK 
                 AGCAGCACATTAACAGCCACCGGGGCATCCAC 
               
               
                   
                 GDECILKDNNERSKWYVTGPGGV 
                 AACTCCATCGGCGACTATCGCTGGC 
               
               
                   
                 DMLVPSVGLIIPPPNPLAVDLSCKI 
                 AGCTGGACAAAATCAAAGCCGACCTGCGCGAG 
               
               
                   
                 EQYYEAILALWNQLYINMKSLVS 
                 AAATCTGCGATCTACCAGTTGGAGGAGGAGTA 
               
               
                   
                 WHYCMIDIEKIRAMTIAKLKTMR 
                 TGAAAACCTGCTGAAAGCGTCCTTTGAGAGGA 
               
               
                   
                 QEDYMKTIADLELHYQEFIRNSQ 
                 TGGATCACCTGCGACAGCTGCAGAACATCATTC 
               
               
                   
                 GSEMFGDDDKRKIQSQFTDAQKH 
                 AGGCCACGTCCAGGGAGATCATGTGGATCAAT 
               
               
                   
                 YQTLVIQLPGYPQHQTVTTTEITH 
                 GACTGCGAGGAGGAGGAGCTGCTGTACGACTG 
               
               
                   
                 HGTCQDVNHNKVIETNRENDKQE 
                 GAGCGACAAGAACACCAACATCGCTCAGAAAC 
               
               
                   
                 TWMLMELQKIRRQIEHCEGRMTL 
                 AGGAGGCCTTCTCCATACGCATGAGTCAACTGG 
               
               
                   
                 KNLPLADQGSSHHITVKINELKSV 
                 AAGTTAAAGAAAAAGAGCTCAATAAGCTGAAA 
               
               
                   
                 QNDSQAIAEVLNQLKDMLANFRG 
                 CAAGAAAGTGACCAACTTGTCCTCAATCAGCAT 
               
               
                   
                 SEKYCYLQNEVFGLFQKLENING 
                 CCAGCTTCAGACAAAATTGAGGCCTATATGGA 
               
               
                   
                 VTDGYLNSLCTVRALLQAILQTE 
                 CACTCTGCAGACGCAGTGGAGTTGGATTCTTCA 
               
               
                   
                 DMLKVYEARLTEEETVCLDLDKV 
                 GATCACCAAGTGCATTGATGTTCATCTGAAAGA 
               
               
                   
                 EAYRCGLKKIKNDLNLKKSLLAT 
                 AAATGCTGCCTACTTTCAGTTTTTTGAAGAGGC 
               
               
                   
                 MKTELQKAQQIHS 
                 GCAGTCTACTGAAGCATACCTGAAGGGGCTCC 
               
               
                   
                 QTSQQYPLYDLDLGKFGEKVTQL 
                 AGGACTCCATCAGGAAGAAGTACCCCTGCGAC 
               
               
                   
                 TDRWQRIDKQIDFRLWDLEKQIK 
                 AAGAACATGCCCCTGCAGCACCTGCTGGAACA 
               
               
                   
                 QLRNYRDNYQAFCKWLYDAKRR 
                 GATCAAGGAGCTGGAGAAAGAACGAGAGAAA 
               
               
                   
                 QDSLESMKEGDSNTVMRFLNEQK 
                 ATCCTTCAATACAAGCGTCAGGTGCAGAACTTG 
               
               
                   
                 NLHSEISOKRDKSEEVQKIAELCA 
                 GTAAACAAGTCTAAGAAGATTGTACAGCTGAA 
               
               
                   
                 NSIKDYELQLASYTSGLETLLNIPI 
                 GCCTCGTAACCCAGACTACAGAAGCAATAAAC 
               
               
                   
                 KRTMIQSPSGVILQEAADVHARYI 
                 CCATTATTCTCAGAGCTCTCTG 
               
               
                   
                 ELLTRSGDYYRFLSEMLKSLEDL 
                 TGACTACAAACAAGATCAGAAAATCGTGCATA 
               
               
                   
                 KLKNTKIEVLEEELRLARDANSEN 
                 AGGGGGATGAGTGTATCCTGAAGGACAACAAC 
               
               
                   
                 CNKNKFLDQNLQKYQAECSQFK 
                 GAGCGCAGCAAGTGGTACGTCACCGGCCCGGG 
               
               
                   
                 AKLASLEELKRQAELDGKSAKQN 
                 AGGCGTTGACATGCTTGTTCCCTCTGTGGCGCT 
               
               
                   
                 IDKCYGQIKIINEKITRLTYEIED 
                 GATCATCCCTCCTCCGAACCCACTGGCCGTGGA 
               
               
                   
                 EKRRRKSVEDRFDQQKNDYDQL 
                 CCTCTCTTGCAAGATTGAGCAGTACTACGAAGC 
               
               
                   
                 QKARQCEKENLGWQKLESEKAIK 
                 CATCTTGGCTCTGTGGAACCAGCTCTACATCAA 
               
               
                   
                 EKEYEIERLRVLIQEEGTRKREYE 
                 CATGAAGAGCCTGGTGTCCTGGCACTACTGCAT 
               
               
                   
                 NELAKVRNHYNEEMSNLRNKYE 
                 GATTGACATAGAGAAGATCAGGGCCATGACAA 
               
               
                   
                 TEINITKTTIKEISMQKEDDSKNLR 
                 TCGCCAAGCTGAAAACAATGCGGCAGGAAGAT 
               
               
                   
                 NQLDRLSRENRDLKDEIVRLNDSI 
                 TACATGAAGACGATAGCCGACCTTGAGTTACAT 
               
               
                   
                 LQATEQRRRAEENALQQKACGSE 
                 TACCAAGAGTTCATCAGAAATAGCCAAGGCTC 
               
               
                   
                 IMQKKQHIEIELKQVMQQRSEDN 
                 AGAGATGTTTGGAGATGATGACAAGCGGAAAA 
               
               
                   
                 ARHKQSLEEAAKTIQDKNKEIERL 
                 TACAGTCTCAGTTCACCGATGCCCAGAAGCATT 
               
               
                   
                 KAEFQEEAKRRWEYENELSKVRN 
                 ACCAGACCCTGGTCATTCAGCTCCCTGGCTATC 
               
               
                   
                 NYDEEIISLKNQFETEINITKTTIHQ 
                 CCCAGCACCAGACAGTGACCACAACTGAAATC 
               
               
                   
                 LTMQKIEDTSGYRAQIDNLTREN 
                 ACTCATCATGGAACCTGCCAAGATGTCAACCAT 
               
               
                   
                 RSLSEEIKRIKNTITQTTENLRRV 
                 AATAAAGTAATTGAAACCAACAGAGAAAATGA 
               
               
                   
                 EEDIQQQKATOSEVSQRKQQLEV 
                 CAAGCAAGAAACATGGATGCTGATGGAGCTGC 
               
               
                   
                 ELRQVTOMRTEESVRYKQSLDDA 
                 AGAAGATTCGCAGGCAGATAGAGCACTGCGAG 
               
               
                   
                 AKTIQDKNKEIERIKQLIDKETND 
                 GGCAGGATGACTCTCAAAAACCTCCCTCTAGCA 
               
               
                   
                 RKCIEDENARLQRVQYDIQKAN 
                 GACCAGGGATCTTCTCACCACATCACAGTGAA 
               
               
                   
                 SSATETINKLKVQEQEITRLRIDY 
                 AATTAACGAGCTTAAGAGTGTGCAGAATGATT 
               
               
                   
                 ERVSQERTVKDQDITRFQNSLKEL 
                 CACAAGCAATTGCTGAGGTTCTCAACCAGCTTA 
               
               
                   
                 QLQKQKVEEELNRLKRTASEDSC 
                 AAGATATGCTTGCCAACTTCAGAGGTTCTGAAA 
               
               
                   
                 KRKKLEEELEGMRRSLKEQAIKIT 
                 AGTACTGCTATTTACAGAATGAAGTATTTGGAC 
               
               
                   
                 NLTQQLEQASIVKKRSEDDLRQQ 
                 TATTTCAGAAACTGGAAAATATCAATGGTGTTA 
               
               
                   
                 RDVLDGHLREKQRTQEELRRLSS 
                 CAGATGGCTACTTAAATAGCTTATGCACAGTAA 
               
               
                   
                 EVEALRRQLLQEQESVKQAHLRN 
                 GGGCACTGCTCCAGGCTATTCTCCAAACAGAA 
               
               
                   
                 EHFQKAIEDKSRSLNESKIEIERLQ 
                 GACATGTTAAAGGTTTATGAAGCCAGGCTCACT 
               
               
                   
                 SLTENLTKEHLMLEEELRNLRLEY 
                 GAGGAGGAAACTGTCTGCCTGGACCTGGATAA 
               
               
                   
                 DDLRRGRSEADSDKNATILELRSQ 
                 AGTGGAAGCTTACCGCTGTGGACTGAAGAAAA 
               
               
                   
                 LQISNNRTLELQGLINDLQREREN 
                 TAAAAAATGA 
               
               
                   
                 LRQEIEKFQKQALEASNRIQESKN 
                 CTTGAACTTGAAGAAGTCGTTGTTGGCCACTAT 
               
               
                   
                 QCTQVVQERESLLVKIKVLEQDK 
                 GAAGACAGAACTACAGAAAGCCCAGCAGATCC 
               
               
                   
                 ARLQRLEDELNRAKSTLEAETRV 
                 ACTCTCAGACTTCACAGCAGTATCCACTTTATG 
               
               
                   
                 KQRLECEKQQIQNDLNQWKTQY 
                 ATCTGGACTTGGGCAAGTTCGGTGAAAAAGTC 
               
               
                   
                 SRKEEAIRKIESEREKSEREKNSLR 
                 ACACAGCTGACAGACCGCTGGCAAAGGATAGA 
               
               
                   
                 SEIERLQAEIKRIEERCRRKLEDST 
                 TAAACAGATCGACTTTAGGTTATGGGACCTGGA 
               
               
                   
                 RETQSQLETERSRYQREIDKLRQR 
                 GAAACAAATCAAGCAATTGAGGAATTATCGTG 
               
               
                   
                 PYGSHRETQTECEWTVDTSKLVF 
                 ATAACTATCAGGCTTTCTGCAAGTGGCTCTATG 
               
               
                   
                 DGLRKKVTAMQLYECQLIDKTTL 
                 ATGCTAAACGCCGCCAGGATTCCTTAGAATCCA 
               
               
                   
                 DKLLKGKKSVEEVASEIQPFLRGA 
                 TGAAATTTGGAGATTCCAACACAGTCATGCGGT 
               
               
                   
                 GSIAGASASPKEKYSLVEAKRKK 
                 TTTTGAATGAGCAGAAGAACTTGC 
               
               
                   
                 LISPESTVMLLEAQAATGGIIDPHR 
                 ACAGTGAAATATCTGGCAAACGAGACAAATCA 
               
               
                   
                 NEKLTVDSAIARDLIDFDDRQQIY 
                 GAGGAAGTACAAAAAATTGCTGAACTTTGCGC 
               
               
                   
                 AAEKAITGFDDPFSGKTVSVSEAI 
                 CAATTCAATTAAGGATTATGAGCTCCAGCTGGC 
               
               
                   
                 KKNLIDRETGMRLLEAQIASGGV 
                 CTCATACACCTCAGGACTGGAAACTCTGCTGAA 
               
               
                   
                 VDPVNSVFLPKDVALARGLIDRD 
                 CATACCTATCAAGAGGACCATGATTCAGTCCCC 
               
               
                   
                 LYR 
                 TTCTGGGGTGATTCTGCAAGAGGCTGCAGATGT 
               
               
                   
                 SLNDPRDSQKNFVDPVTKKKVSY 
                 TCATGCTCGGTACATTGAACTACTTACAAGATC 
               
               
                   
                 VQLKERCRIEPHTGLLLLSVQKRS 
                 TGGAGACTATTACAGGTTCTTAAGTGAGATGCT 
               
               
                   
                 MSFQGIRQPVTVTELVDSGILRPS 
                 GAAGAGTTTGGAAGATCTGAAGCTGAAAAATA 
               
               
                   
                 TVNELESGQISYDEVGERIKDFLQ 
                 CCAAGATCGAAGTTTTGGAAGAGGAGCTCAGA 
               
               
                   
                 GSSCIAGIYNETTKQKLGIYEAMK 
                 CTGGCCCGAGATGCCAACTCGGAAAACTGTAA 
               
               
                   
                 I 
                 TAAGAACAAATTCCTGGATCAGAACCTGCAGA 
               
               
                   
                 GLVRPGTALELLEAQAATGFIVDP 
                 AATACCAGGCAGAGTGTTCCCAGTTCAAAGCG 
               
               
                   
                 VSNLRLPVEEAYKRGLVGIEFKEK 
                 AAGCTTGCGAGCCTGGAGGAGCTGAAGAGACA 
               
               
                   
                 LLSAERAVTOYNDPETGNIISLFQ 
                 GGCTGAGCTGGATGGGAAGTCGGCTAAGCAAA 
               
               
                   
                 AMNKELIEKGHGIRLLEAQIATGG 
                 ATCTAGACAAGTGCTACGGCCAAATAAAAGAA 
               
               
                   
                 IIDPKESHRLPVDIAYKRGYFNEEL 
                 CTCAATGAGAAGATCACCCGACTGACTTATGA 
               
               
                   
                 SEILSDPSDDTKGFFDPNTEENLT 
                 GATTGAAGATGAAAAGAGAAGAAGAAAATCTG 
               
               
                   
                 YLQLKERCIKDEETGLCLLPLKEK 
                 TGGAAGACAGATTTGACCAACAGAAGAATGAC 
               
               
                   
                 KKQVQTSQKNTLRKRRVVIVDPE 
                 TATGACCAACTGCAGAAAGCAAGGCAATGTGA 
               
               
                   
                 TNKEMSVQEAYKKGLIDYETFKE 
                 AAAGGAGAACCTTGGTTGGCAGAAATTAGAGT 
               
               
                   
                 LCEQECEWEEITITGSDGSTRVVL 
                 CTGAGAAAGCCATCAAGGAGAAGGAGTACGAG 
               
               
                   
                 VDRKTGSQYDIQDAIDKGLVDRK 
                 ATTGAAAGGTTGAGGGTTCTACTGCAGGAAGA 
               
               
                   
                 FFDQYRSGSISITQFADMISIKNG 
                 AGGCACCC 
               
               
                   
                 VGTSSSMGSGVSDDVFSSSRHESV 
                 GGAAGAGAGAATATGAAAATGAGCTGGCAAAG 
               
               
                   
                 SKISTISSVRNLTIRSSSFSDTLEES 
                 GTAAGAAACCACTATAATGAGGAGATGAGTAA 
               
               
                   
                 SPIAAIFDTENLEKISITEGIERGIV 
                 TTTAAGGAACAAGTATGAAACAGAGATTAACA 
               
               
                   
                 DSITGQRLLEAQACTGGIIHPTTG 
                 TTACGAAGACCACCATCAAGGAGATATCCATG 
               
               
                   
                 QKLSLQDAVSQGVIDQDMATRLK 
                 CAAAAAGAGGATGATTCCAAAAATCTTAGAAA 
               
               
                   
                 PAQKAFIGFEGVKGKKKMSAAEA 
                 CCAGCTTGATAGACTTTCAAGGGAAAATCGAG 
               
               
                   
                 VKEKWLPYEAGQRFLEFQYLTGO 
                 ATCTGAAGGATGAAATTGTCAGGCTCAATGAC 
               
               
                   
                 LVDPEVHGRISTEEAIRKGFIDGR 
                 AGCATCTTGCAGGCCACTGAGCAGCGAAGGCG 
               
               
                   
                 AAQRIQDTSSYAKILTCPKTKLKI 
                 AGCTGAAGAAAACGCCCTTCAGCAAAAGGCCT 
               
               
                   
                 SYKDAINRSMVEDITGLRLLEAAS 
                 GTGGCTCTGAGATAATGCAGAAGAAGCAGCAT 
               
               
                   
                 VSSKGLPSPYNMSSAPGSRSGSRS 
                 CTGGAGATAGAACTGAAGCAGGTCATGCAGCA 
               
               
                   
                 GSRSGSRSGSRSGSRRGSFDATGN 
                 GCGCTCTGAGGACAATGCCCGGCACAAGCAGT 
               
               
                   
                 SSYSYSYSFSSSSIGH (SEQ ID NO: 
                 CCCTGGAGGAGGCTGCCAAGACCATTCAGGAC 
               
               
                   
                 220) 
                 AAAAATAAGGAGATCGAGAGACTCAAAGCTGA 
               
               
                   
                   
                 GTTTCAGGAGGAGGCCAAGCGCCGCTGGGAAT 
               
               
                   
                   
                 ATGAAAATGAACTGAGTAAGGTAAGAAACAAT 
               
               
                   
                   
                 TATGATGAGGAGATCATTAGCTTAAAAAATCA 
               
               
                   
                   
                 GTTTGAGACCGAGATCAACATCACCAAGACCA 
               
               
                   
                   
                 CCATCCACCAGCTCACCATGCAGAAGGAAGAG 
               
               
                   
                   
                 GATACCAGTGGCTACCGGGCTCAGATAGACAA 
               
               
                   
                   
                 TCTCACCCGAGAAAACAGGAGCTTATCTGAAG 
               
               
                   
                   
                 AAATAAAGAGGCTGAAGAACACTCTAACCCAG 
               
               
                   
                   
                 ACCACAGAGAATCTCAGGAGGGTGGAAGAAGA 
               
               
                   
                   
                 CATCCAACAGCAAAAGGCCACTGGCTCTGAGG 
               
               
                   
                   
                 TGTCTCAGAGGAAACAGCAGCTGGAGGTTGAG 
               
               
                   
                   
                 CTGAGACAAGTCACTCAGATGCGAACAGAGGA 
               
               
                   
                   
                 GAGCGTAAGATATAAGCAATCTCTTGATGATGC 
               
               
                   
                   
                 TGCCAAAACCATCCAGGATAAAAACAAGGAGA 
               
               
                   
                   
                 TAGAAAGGTTAAAACAACTGATCGACAAAGAA 
               
               
                   
                   
                 ACAAATGACCGGAAATGCCTGGAAGATGAAAA 
               
               
                   
                   
                 CGCGAGATTACAAAGGGTCCAGTATGACCTGC 
               
               
                   
                   
                 AGAAAGCAAACAGTAGTGCGACGGAGACAATA 
               
               
                   
                   
                 AACAAACTGAAGGTTCAGGAGCAAGAACTGAC 
               
               
                   
                   
                 ACGCCTGAGGATCGACTATGAAAGGGTTTCCC 
               
               
                   
                   
                 AGGAGAGGACTGTGAAGGACCAGGATATCACG 
               
               
                   
                   
                 CGGTTCCAGAACTCTCTGAAAGAGCTGCAGCTG 
               
               
                   
                   
                 CAGAAGCAGAAGGTGGAAGAGGAGCTGAATCG 
               
               
                   
                   
                 GCTGAAGAGGACCGCGTCAGAAGACTCCTGCA 
               
               
                   
                   
                 AGAGGAAGAAGCTGGAGGAAGAGCTGGAAGG 
               
               
                   
                   
                 CATGAGGAGGTCGCTGAAGGAGCAAGCCATCA 
               
               
                   
                   
                 AAATCACCAACCTGACCCAGCAGCTGGAGCAG 
               
               
                   
                   
                 GCATCCATTCTTAAGAAGAGGAGTGAGGATGA 
               
               
                   
                   
                 CCTCCGGCAGCAGAGGGACGTGCTGGATGGCC 
               
               
                   
                   
                 ACCTGAGGGAAAAGCAGAGGACCCAGGAAGA 
               
               
                   
                   
                 GCTGAGGAGGCTCTCTTCTGAGGTCGAGGCCCT 
               
               
                   
                   
                 GAGGCGGCAGTTACTCCAGGAACAGGAAAGTG 
               
               
                   
                   
                 TCAAACAAGCTCACTTGAGGAATGAGCATTTCC 
               
               
                   
                   
                 AGAAGGCGATAGAAGATAAAAGCAGAAGCTTA 
               
               
                   
                   
                 AATGAAAGCAAAATAGAAATTGAGAGGCTGCA 
               
               
                   
                   
                 GTCTCTCACAGAGAACCTGACCAAGGAGCA 
               
               
                   
                   
                 CTTGATGTTAGAAGAAGAACTGCGGAACCTGA 
               
               
                   
                   
                 GGCTGGAGTACGATGACCTGAGGAGAGGACGA 
               
               
                   
                   
                 AGCGAAGCGGACAGTGATAAAAATGCAACCAT 
               
               
                   
                   
                 CTTGGAACTAAGGAGCCAGCTGCAGATCAGCA 
               
               
                   
                   
                 ACAACCGGACCCTGGAACTGCAGGGGCTGATT 
               
               
                   
                   
                 AATGATTTACAGAGAGAGAGGGAAAATTTGAG 
               
               
                   
                   
                 ACAGGAAATTGAGAAATTCCAAAAGCAGGCTT 
               
               
                   
                   
                 TAGAGGCATCTAATAGGATTCAGGAATCAAAG 
               
               
                   
                   
                 AATCAGTGTACTCAGGTGGTACAGGAAAGAGA 
               
               
                   
                   
                 GAGCCTTCTGGTGAAAATCAAAGTCCTGGAGC 
               
               
                   
                   
                 AAGACAAGCCAAGGCTGCAGAGGCTGGAGGAT 
               
               
                   
                   
                 GAGCTGAATCGTCCAAAATCAACTCTAGAGGC 
               
               
                   
                   
                 AGAAACCAGGGTGAAACAGCGCCTGGAGTGTG 
               
               
                   
                   
                 AGAAACAGCAAATTCAGAATGACCTGAATCAG 
               
               
                   
                   
                 TGGAAGACTCAATATTCCCGCAAGGAGGAGGC 
               
               
                   
                   
                 TATTAGGAAGATAGAATCGGAAAGAGAAAAGA 
               
               
                   
                   
                 GTGAGAGAGAGAAGAACAGTCTTAGGAGTGAG 
               
               
                   
                   
                 ATCGAAAGACTCCAAGCAGAGATCAAGAGAAT 
               
               
                   
                   
                 TGAAGAGAGGTGCAGGCGTAAGCTGGAGGATT 
               
               
                   
                   
                 CTACCAGGGAGACACAGTCACAGTTAGAAACA 
               
               
                   
                   
                 GAACGCTCCCGATATCAGAGGGAGATTGATAA 
               
               
                   
                   
                 ACTCAGACAGCGCCCATATGGGTCCCATCGAG 
               
               
                   
                   
                 AGACCCAGACTGAGTGTGAGTGGACCGTTGAC 
               
               
                   
                   
                 ACCTCCAAGCTGGTGTTTGATGGGCTGAGGAA 
               
               
                   
                   
                 GAAGGTGACAGCAATGCAGCTCTATGAGTGTC 
               
               
                   
                   
                 AGCTGATCGACAAAACAACCTTGGACAAACTA 
               
               
                   
                   
                 TTGAAGGGGAAGAAGTCAGTGGAAGAAGTTGC 
               
               
                   
                   
                 TTCTGAAATCCAGCCATTCCTTCGGGGTGCAGG 
               
               
                   
                   
                 ATCTATCGCTGGAGCATCTGCTTCTCCTAAGGA 
               
               
                   
                   
                 AAAATACTCTTTGGTAGAGGCCAAGAGAAAGA 
               
               
                   
                   
                 AATTAATCAGCCCAGAATCCACAGTCATGCTTC 
               
               
                   
                   
                 TGGAGGCCCAGGCAGCTACAGGTGGTATAATT 
               
               
                   
                   
                 GATCCCCATCGGAATGAGAAGCTGACTGTCGA 
               
               
                   
                   
                 CAGTGCCATAGCTCGGGACCTCATTGACTTCGA 
               
               
                   
                   
                 TGACCGTCAGCAGATATATGCAGCAGAAAAAG 
               
               
                   
                   
                 CTATCACTGGTTTTGATGATCCATTTTCAGGCA 
               
               
                   
                   
                 AGACAGTATCTGTTTCAGAAGCCATCAAGAAA 
               
               
                   
                   
                 AATTTGATTGATAGAGAAACCGGAATGCGCCT 
               
               
                   
                   
                 GCTGGAAGCCCAGATTGCTTCAGGGGGTGTAG 
               
               
                   
                   
                 TAGACGCTGTGAACAGTGTCTTTTTGCCAAAAG 
               
               
                   
                   
                 ATGTCGCCTTGGCCCGGGGGCTGATTGATAGAG 
               
               
                   
                   
                 ATTTGTATCGATCCCTGAATGATCCCCGAGATA 
               
               
                   
                   
                 GTCAGAAAAACTTTGTGGATCCAGTCACCAAA 
               
               
                   
                   
                 AAGAAGGTCAGTTACGTGCAGCTGAAGGAACG 
               
               
                   
                   
                 GTGCAGAATCGAACCACATACTGGTCTGCTCTT 
               
               
                   
                   
                 G 
               
               
                   
                   
                 CTTTCAGTACAGAAGAGAAGCATGTCCTTCCAA 
               
               
                   
                   
                 GGAATCAGACAACCTGTGACCGTCACTGAGCT 
               
               
                   
                   
                 AGTAGATTCTGGTATATTGACACCGTCCACTGT 
               
               
                   
                   
                 CAATGAACTGGAATCTGGTCAGATTTCTTATGA 
               
               
                   
                   
                 CGAGGTTGGTGAGAGAATTAAGGACTTCCTCC 
               
               
                   
                   
                 AGGGTTCAAGCTGCATAGCAGGCATATACAAT 
               
               
                   
                   
                 GAGACCACAAAACAGAAGCTTGGCATTTATGA 
               
               
                   
                   
                 GGCCATGAAAATTGGCTTAGTCCGACCTGGTAC 
               
               
                   
                   
                 TGCTCTGGAGTTGCTGGAAGCCCAAGCAGCTAC 
               
               
                   
                   
                 TGGCTTTATAGTGGATCCTGTTAGCAACTTGAG 
               
               
                   
                   
                 GTTACCAGTGGAGGAAGCCTACAAGAGAGGTC 
               
               
                   
                   
                 TGGTGGGCATTGAGTTCAAAGAGAAGCTCCTGT 
               
               
                   
                   
                 CTGCAGAACGAGCTGTCACTGGGTATAATGATC 
               
               
                   
                   
                 CTGAAACAGGAAACATCATCTCTTTGTTCCAAG 
               
               
                   
                   
                 CCATGAATAAGGAACTCATCGAAAAGGGCCAC 
               
               
                   
                   
                 GGTATTCGCTTATTAGAAGCACAGATCGCAACC 
               
               
                   
                   
                 GGGGGGATCATTGACCCAAAGGAGAGCCATCG 
               
               
                   
                   
                 TTTACCAGTTGACATAGCATATAAGAGGGGCTA 
               
               
                   
                   
                 TTTCAATCAGGAACTCAGTGAGATTCTCTCAGA 
               
               
                   
                   
                 TCCAAGTGATGATACCAAAGGATTTTTTGACCC 
               
               
                   
                   
                 CAACACTGAAGAAAATCTTACCTATCTGCAACT 
               
               
                   
                   
                 AAAAGAAAGATCCATTAAGGATGAGGAAACAG 
               
               
                   
                   
                 GGCTCTGTCTTCTGCCTCTGAAAGAAAAGAAGA 
               
               
                   
                   
                 AACAGGTGCAGACATCACAAAAGAATACCCTC 
               
               
                   
                   
                 AGGAAGCGTAGAGTGGTCATAGTTGACCCAGA 
               
               
                   
                   
                 AACCAATAAAGAAATGTCTGTTCAGGAGGCCT 
               
               
                   
                   
                 ACAAGAAGGGCCTAATTGATTATGAAACCTTC 
               
               
                   
                   
                 AAAGAACTGTGTGAGCAGGAATGTGAATGGGA 
               
               
                   
                   
                 AGAAATAACCATCACGGGATCAGATGGCTCCA 
               
               
                   
                   
                 CCAGGGTGGTCCTGGTAGATAGAAAGACAGGC 
               
               
                   
                   
                 AGTCAGTATGATATTCAAGATGCTATTGACAAG 
               
               
                   
                   
                 GGCCTTGTTGACAGGAAGTTCTTTGATCAGTAC 
               
               
                   
                   
                 CGATCCGGCAGCCTCAGCCTCACTCAATTTGCT 
               
               
                   
                   
                 GACATGATCTCCTTGAAAAATGGTGTCGGCACC 
               
               
                   
                   
                 AGCAGCAGCATGGGCAGTGGTGTCAGCGATGA 
               
               
                   
                   
                 TGTTTTTAGCAGCTCCCGACATGAATCAGTAAG 
               
               
                   
                   
                 TAAGATTTCCACCATATCCAGCGTCAGGAATTT 
               
               
                   
                   
                 AACCATAAGGAGCAGCTCTTTTTCAGACACCCT 
               
               
                   
                   
                 GGAAGAATCGAGCCCCATTGCAGCCATCTTTGA 
               
               
                   
                   
                 CACAGAAAACCTGGAGAAAATCTCCATTACAG 
               
               
                   
                   
                 AAGGTATAGAGCGGGGCATCGTTGACAGCATC 
               
               
                   
                   
                 ACGGGTCAGAGGCTT 
               
               
                   
                   
                 CTGGAGGCTCAGGCCTGCACAGGTGGCATCAT 
               
               
                   
                   
                 CCACCCAACCACGGGCCAGAAGCTGTCACTTC 
               
               
                   
                   
                 AGGACGCAGTCTCCCAGGGTGTGATTGACCAA 
               
               
                   
                   
                 GACATGGCCACCAGGCTGAAGCCTGCTCAGAA 
               
               
                   
                   
                 AGCCTTCATAGGCTTCGAGGGTGTGAAGGGAA 
               
               
                   
                   
                 AGAAGAAGATGTCAGCAGCAGAGGCAGTGAAA 
               
               
                   
                   
                 GAAAAATGGCTCCCGTATGAGGCTGGCCAGCG 
               
               
                   
                   
                 CTTCCTGGAGTTCCAGTACCTCACGGGAGGTCT 
               
               
                   
                   
                 TGTTGACCCGGAAGTGCATGGGAGGATAAGCA 
               
               
                   
                   
                 CCGAAGAAGCCATCCGGAAGGGGTTCATAGAT 
               
               
                   
                   
                 GGCCGCGCCGCACAGAGGCTGCAAGACACCAG 
               
               
                   
                   
                 CAGCTATGCCAAAATCCTGACCTGCCCCAAAAC 
               
               
                   
                   
                 CAAATTAAAAATATCCTATAAGGATGCCATAA 
               
               
                   
                   
                 ATCGCTCCATGGTAGAAGATATCACTGGGCTGC 
               
               
                   
                   
                 GCCTTCTGGAAGCCGCCTCCCTCTCGTCCAAGG 
               
               
                   
                   
                 GCTTACCCAGCCCTTACAACATGTCTTCGGCTC 
               
               
                   
                   
                 CGGGGTCCCGCTCCGGCTCCCGCTCGGGATCTC 
               
               
                   
                   
                 GCTCCGGATCTCGCTCCCGGTCCCGCAGTGGGT 
               
               
                   
                   
                 CCCGGAGAGGAAGCTTTGACGCCACAGGGAAT 
               
               
                   
                   
                 TCTTCCTACTCTTATTCCTACTCATTTAGCAGTA 
               
               
                   
                   
                 GTTCTATTGGGCACTAG (SEQ ID NO: 219) 
               
               
                   
               
               
                 Human DSP 
                 MSCNGGSHPRINTLGRMIRAESGP 
                 ATGAGCTGCAACGGAGGCTCCCACCCGCGGAT 
               
               
                 DPII 
                 DLRYEVTSGGGGTSRMYYSRRG 
                 CAACACTCTGGGCCGCATGATCCGCGCCGAGTC 
               
               
                 isoform 
                 VITDQNSDGYCQTGTMSRHQNQ 
                 TGGCCCGGACCTGCGCTACGAGGTGACCAGCG 
               
               
                   
                 NTIQELLQNCSDCLMRAELIVQPE 
                 GCGGCGGGGGCACCAGCAGGATGTACTATTCT 
               
               
                   
                 LKYGDGIQLTRSRELDECFAQAN 
                 CGGCGCGGCGTGATCACCGACCAGAACTCGGA 
               
               
                   
                 DQMEILDSLIREMRQMGQPCDAY 
                 CGGCTACTGTCAAACCGGCACGATGTCCAGGC 
               
               
                   
                 QKRLLQLQEQMRALYKAISVPRV 
                 ACCAGAACCAGAACACCATCCAGGAGCTGCTG 
               
               
                   
                 RRASSKGGGGYTCQSGSGWDEFT 
                 CAGAACTGCTCCGACTGCTTGATGCGAGCAGA 
               
               
                   
                 KHVTSECLGWMRQQRAEMDMV 
                 GCTCATCGTGCAGCCTGAATTGAAGTATGGAG 
               
               
                   
                 AWGVDLASVEQHINSHRGIHNSI 
                 ATGGAATACAACTGACTCGGAGTCGAGAATTG 
               
               
                   
                 GDYRWQLDKIKADLREKSAIYQL 
                 GATGAGTGTTTTGCCCAGGCCAATGACCAAATG 
               
               
                   
                 EEEYENLLKASFERMDHLRQLQN 
                 GAAATCCTCGACAGCTTGATCAGAGAGATGCG 
               
               
                   
                 IIQATSREIMWINDCEEEELIYDW 
                 GCAGATGGGCCAGCCCTGTGATGCTTACCAGA 
               
               
                   
                 SDKNTNIAQKQEAFSIRMSQLEVK 
                 AAAGGCTTCTTCAGCTCCAAGAGCAAATOCGA 
               
               
                   
                 EKELNKLKQESDQLVLNQHPASD 
                 GCCCTTTATAAAGCCATCAGTGTCCCTCGAGTC 
               
               
                   
                 KIEAYMDTLQTQWSW 
                 CGCAGGGCCAGCTCCAAGGGTGGTGGAGGCTA 
               
               
                   
                 ILQITKCIDVHLKENAAYFQFFEE 
                 CACTTGTCAGAGTGGCTCTGGCTGGGATGAGTT 
               
               
                   
                 AQSTEAYLKGLQDSIRKKYPCDK 
                 CACCAAACATGTCACCAGTGAATGTTTGGGGTG 
               
               
                   
                 NMPLQHLLEQIKELEKEREKILEY 
                 GATGAGGCAGCAAAGGGCGGAGATGGACATGG 
               
               
                   
                 KRQVQNLVNKSKKIVQLKPRNPD 
                 TGGCCTGGGGTGTGGACCTGGCCTCAGTGGAG 
               
               
                   
                 YRSNKPIILRALCDYKQDQKIVHK 
                 CAGCACATTAACAGCCACCGGGGCATCCACAA 
               
               
                   
                 GDECILKDNNERSKWYVTGPGGV 
                 CTCCATCGGCGACTATCGCTGGC 
               
               
                   
                 DMLVPSVGLIIPPPNPLAVDLSCKI 
                 AGCTGGACAAAATCAAAGCCGACCTGCGCGAG 
               
               
                   
                 EQYYEAILALWNQLYINMKSLVS 
                 AAATCTGCGATCTACCAGTTGGAGGAGGAGTA 
               
               
                   
                 WHYCMIDIEKIRAMTIAKLKTMR 
                 TGAAAACCTGCTGAAAGCGTCCTTTGAGAGGA 
               
               
                   
                 QEDYMKTIADLELHYQEFIRNSQ 
                 TGGATCACCTGCGACAGCTGCAGAACATCATTC 
               
               
                   
                 GSEMFGDDDKRKIQSQFTDAQKH 
                 AGGCCACGTCCAGGGAGATCATGTGGATCAAT 
               
               
                   
                 YQTLVIQLPGYPQHQTVTTTEITH 
                 GACTGCGAGGAGGAGGAGCTGCTGTACGACTG 
               
               
                   
                 HGTCQDVNHNKVIETNRENDKQE 
                 GAGCGACAAGAACACCAACATCGCTCAGAAAC 
               
               
                   
                 TWMLMELQKIRRQIEHCEGRMTL 
                 AGGAGGCCTTCTCCATACGCATGAGTCAACTGG 
               
               
                   
                 KNLPLADQGSSHHITVKINELKSV 
                 AAGTTAAAGAAAAAGAGCTCAATAAGCTGAAA 
               
               
                   
                 QNDSQAIAEVLNQLKDMLANFRG 
                 CAAGAAAGTGACCAACTTGTCCTCAATCAGCAT 
               
               
                   
                 SEKYCYLQNEVFGLFQKLENING 
                 CCAGCTTCAGACAAAATTGAGGCCTATATGGA 
               
               
                   
                 VTDGYLNSLCTVRALLQAILQTE 
                 CACTCTGCAGACGCAGTGGAGTTGGATTCTTCA 
               
               
                   
                 DMLKVYEARLTEEETVCLDLDKV 
                 GATCACCAAGTGCATTGATGTTCATCTGAAAGA 
               
               
                   
                 EAYRCGLKKIKNDLNLKKSLLAT 
                 AAATGCTGCCTACTTTCAGTTTTTTGAAGAGGC 
               
               
                   
                 MKTELQKAQQIHS 
                 GCAGTCTACTGAAGCATACCTGAAGGGGCTCC 
               
               
                   
                 QTSQQYPLYDLDLGKFGEKVTQL 
                 AGGACTCCATCAGGAAGAAGTACCCCTGCGAC 
               
               
                   
                 TDRWQRIDKQIDFRLWDLEKQIK 
                 AAGAACATGCCCCTGCAGCACCTGCTGGAACA 
               
               
                   
                 QLRNYRDNYQAFCKWLYDAKRR 
                 GATCAAGGAGCTGGAGAAAGAACGAGAGAAA 
               
               
                   
                 QDSLESMKFGDSNTVMRFLNEQK 
                 ATCCTTGAATACAAGCGTCAGGTGCAGAACTTG 
               
               
                   
                 NLHSEISGKRDKSEEVQKIAELCA 
                 GTAAACAAGTCTAAGAAGATTGTACAGCTGAA 
               
               
                   
                 NSIKDYELQLASYTSGLETLLNIPI 
                 GCCTCGTAACCCAGACTACAGAAGCAATAAAC 
               
               
                   
                 KRTMIQSPSGVILQEAADVHARYI 
                 CCATTATTCTCAGAGCTCTCTG 
               
               
                   
                 ELLTRSGDYYRFLSEMLKSLEDL 
                 TGACTACAAACAAGATCAGAAAATCGTGCATA 
               
               
                   
                 KLKNTKIEVLEEELRLARDANSEN 
                 AGGGGGATGAGTGTATCCTGAAGGACAACAAC 
               
               
                   
                 CNKNKFLDQNLQKYQAECSQFK 
                 GAGCGCAGCAAGTGGTACGTGACGGGCCCGGG 
               
               
                   
                 AKLASLEELKRQAELDGKSAKQN 
                 AGGCGTTGACATGCTTGTTCCCTCTGTGGGGCT 
               
               
                   
                 LDKCYGQIKELNEKITRLTYEIED 
                 GATCATCCCTCCTCCGAACCCACTGGCCGTGGA 
               
               
                   
                 EKRRRKSVEDRFDQQKNDYDQL 
                 CCTCTCTTGCAAGATTGAGCAGTACTACGAAGC 
               
               
                   
                 QKARQCEKENLGWQKLESEKAIK 
                 CATCTTGGCTCTGTGGAACCAGCTCTACATCAA 
               
               
                   
                 EKEYEIERLRVLLQEEGTRKREYE 
                 CATGAAGAGCCTGGTGTCCTGGCACTACTGCAT 
               
               
                   
                 NELAKASNRIQESKNQCTQVVQE 
                 GATTGACATAGAGAAGATCAGGGCCATGACAA 
               
               
                   
                 RESLLVKIKVLEQDKARLQRLED 
                 TCGCCAAGCTGAAAACAATGCGGCAGGAAGAT 
               
               
                   
                 ELNRAKSTIEAETRVKQRLECEK 
                 TACATGAAGACGATAGCCGACCTTGAGTTACAT 
               
               
                   
                 QQ 
                 TACCAAGAGTTCATCAGAAATAGCCAAGGCTC 
               
               
                   
                 IQNDLNQWKTQYSRKEEAIRKIES 
                 AGAGATGTTTCGAGATCATGACAAGCGGAAAA 
               
               
                   
                 EREKSEREKNSLRSEIERLQAEIKR 
                 TACAGTCTCAGTTCACCGATGCCCAGAAGCATT 
               
               
                   
                 IEERCRRKLED 
                 ACCAGACCCTGGTCATTCAGCTCCCTGGCTATC 
               
               
                   
                 STRETQSQLETERSRYQREIDKLR 
                 CCCAGCACCAGACAGTGACCACAACTGAAATC 
               
               
                   
                 QRPYGSHRETQTECEWTVDTSKL 
                 ACTCATCATGGAACCTGCCAAGATGTCAACCAT 
               
               
                   
                 VFDGLRKKVTAMQLYECQLIDKT 
                 AATAAAGTAATTGAAACCAACAGAGAAAATGA 
               
               
                   
                 TLDKLLKGKKSVEEVASEIQPFLR 
                 CAAGCAAGAAACATGGATGCTGATGGAGCTGC 
               
               
                   
                 GAGSTAGASASPKEKYSLVEAKR 
                 AGAAGATTCGCAGGCAGATAGAGCACTGCGAG 
               
               
                   
                 KKLISPESTVMLLEAQAATGGIID 
                 GGCAGGATGACTCTCAAAAACCTCCCTCTAGCA 
               
               
                   
                 PHRNEKLTVDSAIARDLIDFDDRQ 
                 GACCAGGGATCTTCTCACCACATCACAGTGAA 
               
               
                   
                 QIYAAEKAITGFDDPFSGKTVSVS 
                 AATTAACGAGCTTAAGAGTGTGCAGAATGATT 
               
               
                   
                 EAIKKNLIDRETGMRLLEAQIASG 
                 CACAAGCAATTGCTGAGGTTCTCAACCAGCTTA 
               
               
                   
                 GVVDPVNSVFLPKDVALARGLID 
                 AAGATATGCTTGCCAACTTCAGAGGTTCTGAAA 
               
               
                   
                 RDLYRSLNDPRDSQKNFVDPVTK 
                 AGTACTGCTATTTACAGAATGAAGTATTTGGAC 
               
               
                   
                 KKVSYVQLKERCRIEPHTGLLLLS 
                 TATTTCAGAAACTGGAAAATATCAATGGTGTTA 
               
               
                   
                 VQKRSMSFQGIRQPVTVTELVDS 
                 CAGATGGCTACTTAAATAGCTTATGCACAGTAA 
               
               
                   
                 GILRPSTVNELESGQISYDEVGERI 
                 GGGCACTGCTCCAGGCTATTCTCCAAACAGAA 
               
               
                   
                 KDFLQGSSCIAGIYNETTKQKLGI 
                 GACATGTTAAAGGTTTATGAAGCCAGGCTCACT 
               
               
                   
                 YEAMKIOIVRPGTALELLEAQAA 
                 GAGGAGGAAACTGTCTGCCTGGACCTGGATAA 
               
               
                   
                 TGFIVDPVSNLRLPVEEAYKRGLV 
                 AGTGGAAGCTTACCGCTGTGGACTGAAGAAAA 
               
               
                   
                 GIEFKEKLISAERAVTGYNDPETG 
                 TAAAAAATGA (SEQ ID NO: 221) 
               
               
                   
                 NIISLFQAMNKELIEKGHGIRLLEA 
                 CTTGAACTTGAAGAAGTCGTTGTTGGCCACTAT 
               
               
                   
                 QIATGGIIDPKESHRLPVDIAYKRG 
                 GAAGACAGAACTACAGAAAGCCCAGCAGATCC 
               
               
                   
                 YFNEELSEILSDPSDDTKGFFDPNT 
                 ACTCTCAGACTTCACAGCAGTATCCACTTTATG 
               
               
                   
                 EENLTYLQLKERCIKDEETGLCLL 
                 ATCTGGACTTGGGCAAGTTCGGTGAAAAAGTC 
               
               
                   
                 PLKEKKKQVQTSQKNTLRKRRVV 
                 ACACAGCTGACAGACCGCTGGCAAAGGATAGA 
               
               
                   
                 IVDPETNKEMSVQEAYKKGLIDY 
                 TAAACAGATCGACTTTAGGTTATGGGACCTGGA 
               
               
                   
                 ETFKELCEQECEWEEITITGSDGST 
                 GAAACAAATCAAGCAATTGAGGAATTATCGTG 
               
               
                   
                 RVVLVDRKTGSQYDIQDAIDKGL 
                 ATAACTATCAGGCTTTCTGCAAGTGGCTCTATG 
               
               
                   
                 VDRKFFDQYRSGSLSLTQFADMIS 
                 ATGCTAAACGCCGCCAGGATTCCTTAGAATCCA 
               
               
                   
                 LKNGVGTSSSMGSGVSDDVFSSS 
                 TGAAATTTGGAGATTCCAACACAGTCATGCGGT 
               
               
                   
                 RHESVSKISTISSVRNLTIRSSSFSD 
                 TTTTGAATGAGCAGAAGAACTTGC 
               
               
                   
                 TLEESSPIAAIFDTENLEKISITEGIE 
                 ACAGTGAAATATCTGGCAAACGAGACAAATCA 
               
               
                   
                 RGIVDSITGQRLLEAQACTGGIIHP 
                 GAGGAAGTACAAAAAATTGCTGAACTTTGCGC 
               
               
                   
                 TTGQKLSLQDAVSQGVIDQDMAT 
                 CAATTCAATTAAGGATTATGAGCTCCAGCTGGC 
               
               
                   
                 RLKPAQKAFIGFEGVKGKKKMSA 
                 CTCATACACCTCAGGACTGGAAACTCTGCTGAA 
               
               
                   
                 AEAVKEKWLPYEAGQRFLEFQYL 
                 CATACCTATCAAGAGGACCATGATTCAGTCCCC 
               
               
                   
                 TGGLVDPEVHGRISTEEAIRKGFI 
                 TTCTGGGGTGATTCTGCAAGAGGCTGCAGATGT 
               
               
                   
                 DGRAAQRLQDTSSYAKILTCPKT 
                 TCATGCTCGGTACATTGAACTACTTACAAGATC 
               
               
                   
                 KLKISYKDAINRSMVEDITGLRLL 
                 TGGAGACTATTACAGGTTCTTAAGTGAGATGCT 
               
               
                   
                 EAASVSSKGLPSPYNMSSAPGSRS 
                 GAAGAGTTTGGAAGATCTGAAGCTGAAAAATA 
               
               
                   
                 GSRSGSRSGSRSGSRSGSRRGSFD 
                 CCAAGATCGAAGTTTTGGAAGAGGAGCTCAGA 
               
               
                   
                 ATGNSSYSYSYSFSSSSIGH (SEQ 
                 CTGGCCCGAGATGCCAACTCGGAA 
               
               
                   
                 ID NO: 222) 
                 AACTGTAATAAGAACAAATTCCTGGATCAGAA 
               
               
                   
                   
                 CCTGCAGAAATACCAGGCAGAGTGTTCCCAGTT 
               
               
                   
                   
                 CAAAGCGAAGCTTGCGAGCCTGGAGGAGCTGA 
               
               
                   
                   
                 AGAGACAGGCTGAGCTGGATGGGAAGTCGGCT 
               
               
                   
                   
                 AAGCAAAATCTAGACAAGTGCTACGGCCAAAT 
               
               
                   
                   
                 AAAAGAACTCAATGAGAAGATCACCCGACTGA 
               
               
                   
                   
                 CTTATGAGATTGAAGATGAAAAGAGAAGAAGA 
               
               
                   
                   
                 AAATCTGTGGAAGACAGATTTGACCAACAGAA 
               
               
                   
                   
                 GAATGACTATGACCAACTGCAGAAAGCAAGGC 
               
               
                   
                   
                 AATGTGAAAAGGAGAACCTTGGTTGGCAGAAA 
               
               
                   
                   
                 TTAGAGTCTGAGAAAGCCATCAAGGAGAAGGA 
               
               
                   
                   
                 GTACGAGATTGAAAGGTTGAGGGTTCTACTGC 
               
               
                   
                   
                 AGGAAGAAGGCACCC 
               
               
                   
                   
                 GGAAGAGAGAATATGAAAATGAGCTGGCAAAG 
               
               
                   
                   
                 GCATCTAATAGGATTCAGGAATCAAAGAATCA 
               
               
                   
                   
                 GTGTACTCAGGTGGTACAGGAAAGAGAGAGCC 
               
               
                   
                   
                 TTCTGGTGAAAATCAAAGTCCTGGAGCAAGAC 
               
               
                   
                   
                 AAGGCAAGGCTGCAGAGGCTGGAGGATGAGCT 
               
               
                   
                   
                 GAATCGTGCAAAATCAACTCTAGAGGCAGAAA 
               
               
                   
                   
                 CCAGGGTGAAACAGCGCCTGGAGTGTGAGAAA 
               
               
                   
                   
                 CAGCAAATTCAGAATGACCTGAATCAGTGGAA 
               
               
                   
                   
                 GACTCAATATTCCCGCAAGGAGGAGGCTATTA 
               
               
                   
                   
                 GGAAGATAGAATCGGAAAGAGAAAAGAGTGA 
               
               
                   
                   
                 GAGAGAGAAGAACAGTCTTAGGAGTGAGATCG 
               
               
                   
                   
                 AAAGACTCCAAGCAGAGATCAAGAGAATTGAA 
               
               
                   
                   
                 GAGAGGTCCAGGCGTAAGCTGGAGGATTCTAC 
               
               
                   
                   
                 CAGGCAGACACAGTCACAGTTAGAAACAGAAC 
               
               
                   
                   
                 GCT 
               
               
                   
                   
                 CCCGATATCAGAGGGAGATTGATAAACTCAGA 
               
               
                   
                   
                 CAGCGCCCATATGGGTCCCATCGAGAGACCCA 
               
               
                   
                   
                 GACTGAGTGTGAGTGGACCGTTGACACCTCCA 
               
               
                   
                   
                 AGCTGGTGTTTGATGGGCTGAGGAAGAAGGTG 
               
               
                   
                   
                 ACAGCAATGCAGCTCTATGAGTGTCAGCTGATC 
               
               
                   
                   
                 GACAAAACAACCTTGGACAAACTATTGAAGGG 
               
               
                   
                   
                 GAAGAAGTCAGTGGAAGAAGTTGCTTCTGAAA 
               
               
                   
                   
                 TCCAGCCATTCCTTCGGGGTGCAGGATCTATCG 
               
               
                   
                   
                 CTGGAGCATCTGCTTCTCCTAAGGAAAAATACT 
               
               
                   
                   
                 CTTTGGTAGAGGCCAAGAGAAAGAAATTAATC 
               
               
                   
                   
                 AGCCCAGAATCCACAGTCATGCTTCTGGAGGCC 
               
               
                   
                   
                 CAGGCAGCTACAGGTGGTATAATTGATCCCCAT 
               
               
                   
                   
                 CGGAATGAGAAGCTGACTGTCGACAGTGCCAT 
               
               
                   
                   
                 AGCTCGGGACCTCATTGACTTCGATGACCGTCA 
               
               
                   
                   
                 GCAGATATATGCAGCAGAAAAAGCTATCACTG 
               
               
                   
                   
                 GTTTTGATGATCCATTTTCAGGCAAGACAGTAT 
               
               
                   
                   
                 CTGTTTCAGAAGCCATCAAGAAAAATTTGATTG 
               
               
                   
                   
                 ATAGAGAAACCGGAATGCGCCTGCTGGAAGCC 
               
               
                   
                   
                 CAGATTGCTTCAGGGGGTGTAGTAGACCCTGTG 
               
               
                   
                   
                 AACAGTGTCTTTTTGCCAAAAGATGTCGCCTTG 
               
               
                   
                   
                 GCCCGGGGGCTGATTGATAGAGATTTGTATCGA 
               
               
                   
                   
                 TCCCTGAATGATCCCCGAGATAGTCAGAAAAA 
               
               
                   
                   
                 CTTTGTGGATCCAGTCACCAAAAAGAAGGTCA 
               
               
                   
                   
                 GTTACGTGCAGCTGAAGGAACGGTGCAGAATC 
               
               
                   
                   
                 GAACCACATACTGGTCTGCTCTTGCTTTCAGTA 
               
               
                   
                   
                 CAGAAGAGAAGCATGTCCTTCCAAGGAATCAG 
               
               
                   
                   
                 ACAACCTGTGACCGTCACTGAGCTAGTAGATTC 
               
               
                   
                   
                 TGGTATATTGAGACCGTCCACTGTCAATGAACT 
               
               
                   
                   
                 GGAATCTGGTCAGATTTCTTATGACGAGGTTGG 
               
               
                   
                   
                 TGAGAGAATTAAGGACTTCCTCCAGGGTTCAA 
               
               
                   
                   
                 GCTGCATAGCAGGCATATACAATGAGACCACA 
               
               
                   
                   
                 AAACAGAAGCTTGGCATTTATGAGGCCATGAA 
               
               
                   
                   
                 AATTGGCTTAGTCCGACCTGGTACTGCTCTGGA 
               
               
                   
                   
                 GTTGCTGGAAGCCCAAGCAGCTACTGGCTTTAT 
               
               
                   
                   
                 AGTGGATCCTGTTAGCAACTTGAGGTTACCAGT 
               
               
                   
                   
                 GGAGGAAGCCTACAAGAGAGGTCTGGTGGGCA 
               
               
                   
                   
                 TTGAGTTCAAAGAGAAGCTCCTGTCTGCAGAAC 
               
               
                   
                   
                 GAGCTGTCACTGGGTATAATGATCCTGAAACA 
               
               
                   
                   
                 GGAAACATCATCTCTTTGTTCCAAGCCATGAAT 
               
               
                   
                   
                 AAGGAACTCATCGAAAAGGGCCACGGTATTCG 
               
               
                   
                   
                 CTTATTAGAAGCACAGATCGCAACCGGGCGGA 
               
               
                   
                   
                 TCATTGACCCAAAGGACAGCCATCGTTTACCAG 
               
               
                   
                   
                 TTGACATAGCATATAAGAGGGGCTATTTCAATG 
               
               
                   
                   
                 AG 
               
               
                   
                   
                 GAACTCAGTGAGATTCTCTCAGATCCAAGTGAT 
               
               
                   
                   
                 GATACCAAAGGATTTTTTGACCCCAACACTGAA 
               
               
                   
                   
                 GAAAATCTTACCTATCTGCAACTAAAAGAAAG 
               
               
                   
                   
                 ATGCATTAAGGATGAGGAAACAGGGCTCTGTC 
               
               
                   
                   
                 TTCTGCCTCTGAAAGAAAAGAAGAAACAGGTG 
               
               
                   
                   
                 CAGACATCACAAAAGAATACCCTCAGGAAGCG 
               
               
                   
                   
                 TAGAGTGGTCATAGTTGACCCAGAAACCAATA 
               
               
                   
                   
                 AAGAAATGTCTGTTCAGGAGGCCTACAAGAAG 
               
               
                   
                   
                 GOCCTAATTGATTATGAAACCTTCAAAGAACTG 
               
               
                   
                   
                 TGTGAGCAGGAATGTGAATGGGAAGAAATAAC 
               
               
                   
                   
                 CATCACGGGATCAGATGGCTCCACCAGGGTGG 
               
               
                   
                   
                 TCCTGGTAGATAGAAAGACAGGCAGTCAGTAT 
               
               
                   
                   
                 GATATTCAAGATGCTATTGACAAGGGCCTTGTT 
               
               
                   
                   
                 GACAGGAAGTTCTTTGATCAGTACCGATCCGGC 
               
               
                   
                   
                 AGCCTCAGCCTCACTCAATTTGCTGACATGATC 
               
               
                   
                   
                 TCCTTGAAAAATGGTGTCGGCACCAGCAGCAG 
               
               
                   
                   
                 CATGGGCAGTGGTGTCAGCGATGATGTTTTTAG 
               
               
                   
                   
                 CAGCTCCCGACATGAATCAGTAAGTAAGATTTC 
               
               
                   
                   
                 CACCATATCCAGCGTCAGGAATTTAACCATAAG 
               
               
                   
                   
                 GAGCAGCTCTTTTTCAGACACCCTGGAAGAATC 
               
               
                   
                   
                 GAGCCCCATTGCAGCCATCTTTGACACAGAAA 
               
               
                   
                   
                 ACCTGGAGAAAATCTCCA 
               
               
                   
                   
                 TTACAGAAGGTATAGAGCGGGGCATCGTTGAC 
               
               
                   
                   
                 AGCATCACGGGTCAGAGGCTTCTGGAGGCTCA 
               
               
                   
                   
                 GGCCTGCACAGGTGGCATCATCCACCCAACCA 
               
               
                   
                   
                 CGGGCCAGAAGCTGTCACTTCAGGACGCAGTC 
               
               
                   
                   
                 TCCCAGGGTGTGATTGACCAAGACATGGCCAC 
               
               
                   
                   
                 CAGGCTGAAGCCTGCTCAGAAAGCCTTCATAG 
               
               
                   
                   
                 GCTTCGAGGGTGTGAAGGGAAAGAAGAAGATG 
               
               
                   
                   
                 TCAGCAGCAGAGGCAGTGAAAGAAAAATGGCT 
               
               
                   
                   
                 CCCGTATGAGGCTGGCCAGCGCTTCCTGGAGTT 
               
               
                   
                   
                 CCAGTACCTCACGGGAGGTCTTGTTGACCCGGA 
               
               
                   
                   
                 AGTGCATGGGAGGATAAGCACCGAAGAAGCCA 
               
               
                   
                   
                 TCCGGAAGGGGTTCATAGATGGCCGCGCCGCA 
               
               
                   
                   
                 CAGAGGCTGCAAGACACCAGCAGCTATGCCAA 
               
               
                   
                   
                 AATCCTGACCTGCCCCAAAACCAAATTAAAAA 
               
               
                   
                   
                 TATCCTATAAGGATGCCATAAATCGCTCCATGG 
               
               
                   
                   
                 TAGAAGATATCACTGGGCTGCGCCTTCTGGAAG 
               
               
                   
                   
                 CCGCCTCCGTGTCGTCCAAGGGCTTACCCAGCC 
               
               
                   
                   
                 CTTACAACATGTCTTCGGCTCCGGGGTCCCGCT 
               
               
                   
                   
                 CCGGCTCCCGCTCGGGATCTCGCTCCGGATCTC 
               
               
                   
                   
                 GCTCCGGGTCCCGCAGTGGGTCCCGGAGAGGA 
               
               
                   
                   
                 AGCTTTGACGCCACAGGGAATTCTTCCTACTCT 
               
               
                   
                   
                 TATTCCTACTCATTTAGCAGTAGTTCTATTGGG 
               
               
                   
                   
                 CACTAG (SEQ ID NO: 221) 
               
               
                   
               
               
                 Human 
                 MARSPGRAYALLLLLICFNVGSG 
                 ATGGCGCGGAGCCCGGGACGCGCGTACGCCCT 
               
               
                 DSG2 
                 LHLQVISTRNENKLLPKHPHLVR 
                 GCTGCTTCTCCTGATCTGCTTTAACGTTGGAAG 
               
               
                   
                 QKRAWITAPVALREGEDLSKKNP 
                 TGGACTTCACTTACAGGTCTTAAGCACAAGAAA 
               
               
                   
                 IAKIHSDLAEERGLKITYKYTGKG 
                 TGAAAATAAGCTGCTTCCTAAACATCCTCATTT 
               
               
                   
                 ITEPPFGIFVFNKDTGELNVTSILD 
                 AGTGCGGCAAAAGCGCGCCTGGATCACCGCCC 
               
               
                   
                 REETPFFILTGYAIDARGNNVEK 
                 CCGTGGCTCTTCGGGAGGGAGAGGATCTGTCC 
               
               
                   
                 PLELRIKVLDINDNEPVFTQDVFV 
                 AAGAAGAATCCAATTGCCAAGATACATTCTGA 
               
               
                   
                 GSVEELSAAHTLVMKINATDADE 
                 TCTTGCAGAAGAAAGAGGACTCAAAATTACTT 
               
               
                   
                 PNTLNSKISYRIVSLEPAYPPVFYL 
                 ACAAATACACTGGAAAAGGGATTACAGAGCCA 
               
               
                   
                 NKDTGEIYTTSVTLDREEHSSYTL 
                 CCTTTTGGTATATTTGTCTTTAACAAAGATACT 
               
               
                   
                 TVEARDGNGEVTDKPVKQAQVQI 
                 GGAGAACTGAATGTTACCAGCATTCTTGATCGA 
               
               
                   
                 RILDVNDNIPVVENKVLEGMVEE 
                 GAAGAAACACCATTTTTCTGCTAACAGGTTAC 
               
               
                   
                 NQVNVEVTRIKVFDADEIGSDNW 
                 GCTTTGGATGCAAGAGGAAACAATGTAGAGAA 
               
               
                   
                 LANFTFASGNEGGYFHIETDAQT 
                 ACCCTTAGAGCTACGCATTAAGGTTCTTGATAT 
               
               
                   
                 NEGIVTLIKEVDYEEMKNLDFSVI 
                 CAATGACAACGAACCAGTGTTCACACAGGATG 
               
               
                   
                 VANKAAFHKSIRSKYKPTPIPIKV 
                 TCTTTGTTGGGTCTGTTGAAGAGTTGAGTGCAG 
               
               
                   
                 KVKNVKEGIHFKSSVISIYVSESM 
                 CACATACTCTTGTGATGAAAATCAATGCAACAG 
               
               
                   
                 DRSSKGQIIGNFQAFDEDTGLPAH 
                 ATGCAGATGAGCCCAATACCCTGAATTCGAAA 
               
               
                   
                 ARYVKLEDRDNWISVDSVTSEIK 
                 ATTTCCTATAGAATCGTATCTCTGGAGCCTGCT 
               
               
                   
                 LAKLPDFESRYVQNGTYTVKIVAI 
                 TATCCTCCAGTGTTCTACCTAAATAAAGATACA 
               
               
                   
                 SEDYPRKTITOTVLINVEDINDNC 
                 GGAGAGATTTATACAACCAGTGTTACCTTGGAC 
               
               
                   
                 PTLIEPVQTICHDAEYVNVTAEDL 
                 AGAGAGGAACACAGCAGCTACACTTTGACAGT 
               
               
                   
                 DGHPNSOPFSFSVIDKPPGMAEK 
                 AGAAGCAAGAGATGGCAATGGAGAAGTTACAG 
               
               
                   
                 WKIARQESTSVLLQQSEKKLGRS 
                 ACAAACCTGTAAAACAAGCTCAAGTTCAGATT 
               
               
                   
                 EIQFLISDNQGFSCPEKQVLTITVC 
                 CGTATTTTGGATGTCAATGACAATATACCTGTA 
               
               
                   
                 ECIHGSGCREAQHDSYVGLGPAA 
                 GTAGAAAATAAAGTGCTTGAAGGGATGGTTGA 
               
               
                   
                 IALMILAFLLLLLVPLLLLMCHCG 
                 AGAAAATCAAGTCAACGTAGAAGTTACGCGCA 
               
               
                   
                 KGAKGETPIPGTIEMLHPWNNEG 
                 TAAAAGTGTTCGATGCAGATGAAATAGGTTCTG 
               
               
                   
                 APPEDKVVPSFLPVDQGGSLVGR 
                 ATAATTGGCTGGCAAATTTTACATTTGCATCAG 
               
               
                   
                 NGVGGMAKEATMKGSSSASIVK 
                 GAAATGA 
               
               
                   
                 GQHEMSEMDGRWEEHRSLLSGR 
                 AGGAGGTTATTTCCACATAGAAACAGATGCTC 
               
               
                   
                 ATQFTGATGAIMTTETTKTARAT 
                 AAACTAACGAAGGAATTGTGACCCTTATTAAG 
               
               
                   
                 GASRDMAGAQAAAVALNEEFLR 
                 GAAGTAGATTATGAAGAAATGAAGAATCTTGA 
               
               
                   
                 NYFTDKAASYTEEDENHTAKDCL 
                 CTTCAGTGTTATTGTCGCTAATAAAGCAGCTTT 
               
               
                   
                 LVYSQEETESLNASIGCCSFIEGEL 
                 TCACAAGTCGATTAGGAGTAAATACAAGCCTA 
               
               
                   
                 DDRFLDDLGLKFKTLAEVCLGQK 
                 CACCCATTCCCATCAAGGTCAAAGTGAAAAAT 
               
               
                   
                 IDINKEIEQRQKPATETSMNTASH 
                 GTGAAAGAAGGCATTCATTTTAAAAGCAGCGT 
               
               
                   
                 SLCEQTMVNSENTYSSGSSFPVPK 
                 CATCTCAATTTATGTTAGCGAGAGCATGGATAG 
               
               
                   
                 SLQEANAEKVTQEIVTERSVSSRQ 
                 ATCAAGCAAAGGCCAAATAATTGGAAATTTTC 
               
               
                   
                 AQKVATPLPDPMASRNVIATETS 
                 AAGCTTTTGATGAGGACACTGGACTACCAGCCC 
               
               
                   
                 YVTGSTMPPTTVILGPSQPQSLIVT 
                 ATGCAAGATATGTAAAATTAGAAGATAGAGAT 
               
               
                   
                 ERVYAPASTLVDQPYANEGTVVV 
                 AATTGGATCTCTGTGGATTCTGTCACATCTGAA 
               
               
                   
                 TERVIQPHGGGSNPLEGTQHLQD 
                 ATTAAACTTGCAAAACTTCCTGATTTTGAATCT 
               
               
                   
                 VPYVMVRERESFLAPSSGVQPTL 
                 AGATATGTTCAAAATGGCACATACACTGTAAA 
               
               
                   
                 AMPNIAVGQNVTVTERVLAPAST 
                 GATTGTGGCCATATCAGAAGATTATCCTAGAAA 
               
               
                   
                 LQSSYQIPTENSMTARNTTVSGAG 
                 AACCATCACTGGCACAGTCCTTATCAATGTTGA 
               
               
                   
                 VPGPLPDFGLEESGHSNSTITTSST 
                 AGACATCAACGACAACTGTCCCACACTGATAG 
               
               
                   
                 RVTKHSTVQHSYS (SEQ ID NO: 
                 AGCCTGTGCAGACAATCTGTCACGATGCAGAG 
               
               
                   
                 224) 
                 TATGTGAATGTTACTGCAGAGGACCTGGATGG 
               
               
                   
                   
                 ACACCCAAACAGTGGCCCTTTCAGTTTCTCCGT 
               
               
                   
                   
                 CATTGACAAACCACCTGGCATGGCAGAAAAAT 
               
               
                   
                   
                 GGAAAATAGCACGCCAAGAAAGTACCAGTGTG 
               
               
                   
                   
                 CTGCTGCAACAAAGTGAGAAAAAGCTTGGGAG 
               
               
                   
                   
                 AAGTGAAATTCAGTTCCTGATTTCAGACAATCA 
               
               
                   
                   
                 GGGTTTTAGTTGTCCTGAAAAGCAGGTCCTTAC 
               
               
                   
                   
                 ACTCACAGTTTGTGAGTGTCTGCATGGCAGCGG 
               
               
                   
                   
                 CTGCAGGGAAGCACAGCATGACTCCTATGTGG 
               
               
                   
                   
                 GCCTGGGACCCGCAGCAATTGCGCTCATGATTT 
               
               
                   
                   
                 TGGCCTTTCTGCTCCTGCTATTGGTACCACTTTT 
               
               
                   
                   
                 ACTGCTGA 
               
               
                   
                   
                 TGTGCCATTGCGGAAAGGGCGCCAAAGGCTTT 
               
               
                   
                   
                 ACCCCCATACCTGGCACCATAGAGATGCTGCAT 
               
               
                   
                   
                 CCTTGGAATAATGAAGGAGCACCACCTGAAGA 
               
               
                   
                   
                 CAAGGTGGTGCCATCATTTCTGCCAGTGGATCA 
               
               
                   
                   
                 AGGGGGCAGTCTAGTAGGAAGAAATGGAGTAG 
               
               
                   
                   
                 GAGGTATGGCCAAGGAAGCCACGATGAAAGGA 
               
               
                   
                   
                 AGTAGCTCTGCTTCCATTGTCAAAGGGCAACAT 
               
               
                   
                   
                 GAGATGTCCGAGATGGATGGAAGGTGGGAAGA 
               
               
                   
                   
                 ACACAGAAGCCTGCTTTCTGGTAGAGCTACCCA 
               
               
                   
                   
                 GTTTACAGGGGCCACAGGCGCTATCATGACCA 
               
               
                   
                   
                 CTGAAACCACGAAGACCGCAAGGGCCACAGGG 
               
               
                   
                   
                 GCTTCCAGAGACATGGCCGGAGCTCAGGCAGC 
               
               
                   
                   
                 TGCTGTTGCACTGAACGAAGAATTCTTAAGAAA 
               
               
                   
                   
                 TTATTTCACTGATAAAGCGGCCTCTTACACTGA 
               
               
                   
                   
                 GGAAGATGAAAATCACACAGCCAAAGATTGCC 
               
               
                   
                   
                 TTCTGGTTTATTCTCAGGAAGAAACTGAATCGC 
               
               
                   
                   
                 TGAATGCTTCTATTGCTTGTTGCAGTTTTATTGA 
               
               
                   
                   
                 AGGAGAGCTACATGACCGCTTCTTAGATCATTT 
               
               
                   
                   
                 GGGACTTAAATTCAAGACACTAGCTGAAGTTTG 
               
               
                   
                   
                 CCTGGGTCAAAAAATAGATATAAATAAGGAAA 
               
               
                   
                   
                 TTGAGCAGAGACAAAAACCTGCCACAGAAACA 
               
               
                   
                   
                 AGTATGAACACAGCTTC 
               
               
                   
                   
                 ACATTCACTCTGTGAGCAAACTATGGTTAATTC 
               
               
                   
                   
                 AGAGAATACCTACTCCTCTGGCAGTAGCTTCCC 
               
               
                   
                   
                 AGTTCCAAAATCTTTGCAAGAAGCCAATGCAG 
               
               
                   
                   
                 AGAAAGTAACTCAGGAAATAGTCACTGAAAGA 
               
               
                   
                   
                 TCTGTGTCTTCTAGGCAGGCGCAAAAGGTAGCT 
               
               
                   
                   
                 ACACCTCTTCCTGACCCAATGGCTTCTAGAAAT 
               
               
                   
                   
                 GTGATAGCAACAGAAACTTCCTATGTCACAGG 
               
               
                   
                   
                 GTCCACTATGCCACCAACCACTGTGATCCTGGG 
               
               
                   
                   
                 TCCTAGCCAGCCACAGAGCCTTATTGTGACAGA 
               
               
                   
                   
                 GAGGGTGTATGCTCCAGCTTCTACCTTGGTAGA 
               
               
                   
                   
                 TCAGCCTTATGCTAATGAAGGTACAGTTGTGGT 
               
               
                   
                   
                 CACTGAAAGAGTAATACAGCCTCATGGGGGTG 
               
               
                   
                   
                 GATCGAATCCTCTGGAAGGCACTCAGCATCTTC 
               
               
                   
                   
                 AAGATGTACCTTACGTCATGGTGAGGGAAAGA 
               
               
                   
                   
                 GAGAGCTTCCTTGCCCCCAGCTCAGGTGTGCAG 
               
               
                   
                   
                 CCTACTCTGGCCATGCCTAATATAGCAGTAGGA 
               
               
                   
                   
                 CAGAATGTGACAGTGACAGAAAGAGTTCTAGC 
               
               
                   
                   
                 ACCTGCTTCCACTCTGCAATCCAGTTACCAGAT 
               
               
                   
                   
                 TCCCACTGAAAATTCTATGACGGCTAGGAACAC 
               
               
                   
                   
                 CACGGTGTCTGGAGCTGGAGTCCCTGGCC 
               
               
                   
                   
                 CTCTGCCAGATTTTGGTTTAGAGGAATCTGGTC 
               
               
                   
                   
                 ATTCTAATTCTACCATAACCACATCTTCCACCA 
               
               
                   
                   
                 GAGTTACCAAGCATAGCACTGTACAGCATTCTT 
               
               
                   
                   
                 ACTCCTAA (SEQ ID NO: 223) 
               
               
                   
               
               
                 Human JUP 
                 MEVMNLMEQPIKVTEWQQTYTY 
                 ATGGAGGTGATGAACCTGATGGAGCAGCCTAT 
               
               
                   
                 DSGIHSGANTCVPSVSSKGIMEED 
                 CAAGGTGACTGAGTGGCAGCAGACATACACCT 
               
               
                   
                 EACGRQYTLKKTTTYTQGVPPSQ 
                 ACGACTCGGGTATCCACTCGGGCGCCAACACCT 
               
               
                   
                 GDLEYQMSTTARAKRVREAMCP 
                 GCGTGCCCTCCGTCAGCAGCAAGGGCATCATG 
               
               
                   
                 GVSGEDSSLLLATQVEGQATNLQ 
                 GAGGAGGATGAGGCCTGCGGGCGCCAGTACAC 
               
               
                   
                 RLAEPSQLLKSAIVHLINYQDDAE 
                 GCTCAAGAAAACCACCACTTACACCCAGGGGG 
               
               
                   
                 LATRALPEITKLLNDEDPVVVTK 
                 TGCCCCCCAGCCAAGGTGATCTGGAGTACCAG 
               
               
                   
                 AAMIVNQLSKKEASRRALMGSPQ 
                 ATGTCCACAACAGCCAGGGCCAAACGGGTGCG 
               
               
                   
                 LVAAVVRTMQNTSDLDTARCTTS 
                 GGAGGCCATGTGCCCTGGTGTGTCAGGCGAGG 
               
               
                   
                 ILHNLSHHREGLLAIFKSGGIPALV 
                 ACAGCTCGCTTCTGCTGGCCACCCAGGTGGAGG 
               
               
                   
                 RMLSSPVESVLFYAITTLHNLLLY 
                 GGCAGGCCACCAACCTGCAGCGACTGGCCGAG 
               
               
                   
                 QEGAKMAVRLADGLQKMVPLLN 
                 CCGTCCCAGCTGCTCAAGTCGGCCATTGTGCAT 
               
               
                   
                 KNNPKFLAITTDCLQLLAYGNQE 
                 CTCATCAACTACC 
               
               
                   
                 SKLIILANGGPQALVQIMRNYSYE 
                 AGGACGATGCCGAGCTGGCCACTCGCGCCCTG 
               
               
                   
                 KLLWTTSRVLKVLSVCPSNKPAIV 
                 CCCGAGCTCACCAAACTGCTCAACGACGAGGA 
               
               
                   
                 EAGGMQALGKHLTSNSPRLVQN 
                 CCCGGTGGTGGTGACCAAGGCGGCCATGATTG 
               
               
                   
                 CLWTLRNLSDVATKQEGLESVLK 
                 TGAACCAGCTGTCGAAGAAGGAGGCGTCGCGG 
               
               
                   
                 ILVNQLSVDDVNVLTCATGTLSN 
                 CGGGCCCTGATGGGCTCGCCCCAGCTGGTGGCC 
               
               
                   
                 LTCNNSKNKTLVTQNSGVEALIH 
                 GCTGTCGTGCGTACCATGCAGAATACCAGCGA 
               
               
                   
                 AILRAGDKDDITEPAVCALRHLTS 
                 CCTGGACACAGCCCGCTGCACCACCAGCATCCT 
               
               
                   
                 RHPEAEMAQNSVRLNY 
                 GCACAACCTCTCCCACCACCGGGAGGGGCTGC 
               
               
                   
                 GIPAIVKLLNQPNQWPLVKATIGL 
                 TCGCCATCTTCAAGTCGGGTGGCATCCCTGCTC 
               
               
                   
                 IRNLALCPANHAPLQEAAVIPRLV 
                 TGGTCCGCATGCTCAGCTCCCCTGTGGAGTCGG 
               
               
                   
                 QLLVKAHQDAQRHVAAGTQQPY 
                 TCCTGTTCTATGCCATCACCACGCTGCACAACC 
               
               
                   
                 TDGVRMEEIVEGCTGALHILARD 
                 TGCTCCTGTACCAGGAGGGCGCCAAGATGGCC 
               
               
                   
                 PMNRMEIFRLNTIPIFVQLLYSSV 
                 GTGCGCCTGGCCGACGGGCTGCAAAAGATGGT 
               
               
                   
                 ENIQRVAAGVLCELAQDKEAADA 
                 GCCCCTGCTCAACAAGAACAACCCCAAGTTCCT 
               
               
                   
                 IDAEGASAPLMELIHSRNEGTAT 
                 GGCCATCACCACCGACTGCCTGCAGCTCCTGGC 
               
               
                   
                 YAAAVLFRISEDKNPDYRKRVSV 
                 CTACGGCAACCAGGAGAGCAAGCTGATCATCC 
               
               
                   
                 ELTNSLFKHDPAAWEAAQSMIPIN 
                 TGGCCAATGGTGGGCCCCAGGCCCTCGTGCAG 
               
               
                   
                 EPYGDDMDATYRPMYSSDVPLDP 
                 ATCATGCGTAACTACAGTTATGAAAAGCTGCTC 
               
               
                   
                 LEMHMDMDGDYPIDTYSDGLRPP 
                 TGGACCACCAGTCGTGTGCTCAAGGTGCTATCC 
               
               
                   
                 YPTADHMLA (SEQ ID NO: 226) 
                 GTGTGTCCCAGCAATAAGCCTGCCATTGTGGAG 
               
               
                   
                   
                 GCTGGTGGGATGCAGGCCCTGGGCAAGCACCT 
               
               
                   
                   
                 GACCAGCAACAGCCCCCGCCTGGTGCAGAACT 
               
               
                   
                   
                 GCCTGTGGACCCTGCGCAACCTCTCAGATGTGG 
               
               
                   
                   
                 CCACCAAGCAGGAGGGCCTGGAGAGTGTGCTG 
               
               
                   
                   
                 AAGATTCTGGTGAATCAGCTGAGTGTGGATGA 
               
               
                   
                   
                 CGTCAACGTCCTCACCTGTGCCACGGGCACACT 
               
               
                   
                   
                 CTCCAACCTGACATGCAACAACAGCAAGAACA 
               
               
                   
                   
                 AGACGCTGGTGACACAGAACAGCGGTGTGGAG 
               
               
                   
                   
                 GCTCTCATCCATGCCATCCTGCGTGCTGGTGAC 
               
               
                   
                   
                 AAGGACGACATCACGGAGCCTGCCGTCTGCGC 
               
               
                   
                   
                 TCTGCGCCACCTCACTAGCCGCCACCCTGAGGC 
               
               
                   
                   
                 CGAGATGGCCCAGAACTCTGTGCGTCTCAACTA 
               
               
                   
                   
                 TGGCATCCCAGCCATCGTGAAGCTGCTCAACCA 
               
               
                   
                   
                 GCCCAACCAGTGGCCACTGGTCAAGGCAACCA 
               
               
                   
                   
                 TCGGCTTGATCAGGAATCTGGCCCTGTGCCCAG 
               
               
                   
                   
                 CCAACCATGCCCCGCTGCAGGAGGCAGCGGTC 
               
               
                   
                   
                 ATCCCCCGCCTCGTCCAACTGCTGGTGAAGGCC 
               
               
                   
                   
                 CACCAGGATGCCCAGCGCCACGTAGCTGCAGG 
               
               
                   
                   
                 CACACAGCAGCCCTACACGGATGGTGTGAGGA 
               
               
                   
                   
                 TGGAGGAGATTGTGGAGGGCTGCACCGGAGCA 
               
               
                   
                   
                 CTGCACATCCTCGCCCGGGACCCCATGAACCGC 
               
               
                   
                   
                 ATGGAGATCTTCCGGCTCAACACCATTCCCCTG 
               
               
                   
                   
                 TTTGTGCAGCTCCTGTACTCGTCGGTGGAGAAC 
               
               
                   
                   
                 ATCCAGCGCGTGGCTGCCGGGGTGCTGTGTGA 
               
               
                   
                   
                 GCTGGCCCAGGACAAGGAGGCGGCCGACGCCA 
               
               
                   
                   
                 TTGATGCAGAGGGGGCCTCGGCCCCACTCATG 
               
               
                   
                   
                 GAGTTGCTGCACTCCCGCAACGAGGGCACTGC 
               
               
                   
                   
                 CACCTACGCTGCTGCCGTCCTGTTCCGCATCTC 
               
               
                   
                   
                 CGAGGACAAGAACCCAGACTACCGGAAGCGCG 
               
               
                   
                   
                 TGTCCGTGGAGCTCACCAACTCCCTCTTCAAGC 
               
               
                   
                   
                 ATGACCCGGCTGCCTGGGAGGCTGCCCAGAGC 
               
               
                   
                   
                 ATGATTCCCATCAATGAGCCCTATGGAGATGAC 
               
               
                   
                   
                 ATGGATGCCACCTACCGCCCCATGTACTCCAGC 
               
               
                   
                   
                 GATGTGCCCCTTGACCCGCTGGAGATGCACATG 
               
               
                   
                   
                 GACATGGATGGAGACTACCCCATCGACACCTA 
               
               
                   
                   
                 CACCGACGCCCTCAGGCCCCCCTACCCCACTCC 
               
               
                   
                   
                 AGACCACATGCTGGCCTAG (SEQ ID NO: 225) 
               
               
                   
               
               
                 Human 
                 MSGGRFDFDDGGAYCGGWEGGK 
                 ATGAGTGGGGGCCGCTTCGACTTTGATGATGGA 
               
               
                 JPH2 N- 
                 AHGHGLCTGPKGQGEYSGSWNF 
                 GGGGCGTACTGCGGGGGCTGGGAGGGGGGAAA 
               
               
                 terminal 
                 GFEVAGVYTWPSGNTFEGYWSQ 
                 GGCCCATGGGCATGGACTGTGCACAGGCCCCA 
               
               
                 fragment 
                 GKRHGLGIETKGRWLYKGEWTH 
                 AGGGCCAGGGCGAATACTCTGGCTCCTGGAAC 
               
               
                   
                 GFKGRYGIRQSSSSGAKYEGTWN 
                 TTTGGCTTTGAGGTGGCAGGTGTCTACACCTGG 
               
               
                   
                 NGLQDGYGTETYADGGTYQGQF 
                 CCCAGCGGAAACACCTTTGAGGGATACTGGAG 
               
               
                   
                 TNGMRHGYGVRQSVPYGMAVV 
                 CCAGGGCAAACGGCATGGGCTGGGCATAGAGA 
               
               
                   
                 VRSPLRTSLSSLRSEHSNGTVAPD 
                 CCAAGGGGCGCTGGCTCTACAAGGGCGAGTGG 
               
               
                   
                 SPASPASDGPALPSPAIPRGGFALS 
                 ACACATGGCTTCAAGGGACGCTACGGAATCCG 
               
               
                   
                 LLANAEAAARAPKGGGLFQRGA 
                 GCAGAGCTCAAGCAGCGGTGCCAAGTATGAGG 
               
               
                   
                 LLGKLRRAESRTSVGSQRSRVSFL 
                 GCACCTGGAACAATGGCCTGCAAGACGGCTAT 
               
               
                   
                 KSDLSSGASDAASTASLGEAAEG 
                 GGCACCGAGACCTATGCTGATGGAGGGACGTA 
               
               
                   
                 ADEAAPFEADIDATTTETYMGEW 
                 CCAAGGCCAGTTCACCAACGGCATGCGCCATG 
               
               
                   
                 KNDKRSGFGVSERSSGLRYEGEW 
                 GCTACGGAGTACGCCAGAGCGTGCCCTACGGG 
               
               
                   
                 LDNLRHGYGCTTLPDGHREEGKY 
                 ATGGCCGTGGTGGTGCGCTCGCCGCTGCGCACG 
               
               
                   
                 RHNVLVKDTKRRMIQIKSNKVR 
                 TCGCTGTCGTCCCTGCGCAGCGAGCACAGCAAC 
               
               
                   
                 QKVEHSVEGAQRAAAIARQKAEI 
                 GGCACGGTGGCCCCGGACTCTCCCGCCTCGCCG 
               
               
                   
                 AASRTSHAKAKAEAAEQAALAA 
                 GCCTCCGACGGCCCCGCGCTGCCCTCGCCCGCC 
               
               
                   
                 NQESNIARTLARELAPDFYQPGPE 
                 ATCCCGCGTGGCGGCTTCGCGCTCAGCCTCCTG 
               
               
                   
                 YQKRRLLQEILENSESLLEPPDRG 
                 GCCAATGCCGAGGCGGCCGCGCGGGCGCCCAA 
               
               
                   
                 AGAAGLPQPPRESPQLHERETPRP 
                 GGGCGGCGGCCTCTTCCAGCGGGGCGCGCTGC 
               
               
                   
                 EGGSPSPAGTPPQPKRPRPGVSKD 
                 TGGGCAAGCTGCGGCGCGCAGAGTCGCGCACG 
               
               
                   
                 GLLSPGAWNGEPSGEGSRSVTPSE 
                 TCCGTGGGTAGCCAGCGCAGCCGTGTCAGCTTC 
               
               
                   
                 GAGRRSPARPATERMAIEALQAP 
                 CTTAAGAGCGACCTCAGCTCGGGCGCCAGCGA 
               
               
                   
                 PAPSREPEVALYQGYHSYAVR 
                 CGCCGCGTCCACCGCCAGCCTGGGAGAGGCCG 
               
               
                   
                 (SEQ ID NO: 228) 
                 CCGAGGGCGCCGACGAGGCCGCACCCTTCGAG 
               
               
                   
                   
                 GCCGATATCGACGCCACCACCACCGAGACCTA 
               
               
                   
                   
                 CATGGGCGAGTGGAAGAACGACAAACGCTCGG 
               
               
                   
                   
                 GCTTCGGCGTGAGCGAACGCTCCAGTGGCCTCC 
               
               
                   
                   
                 GCTACGAGGGCGAGTGGCTGGACAACCTGCGC 
               
               
                   
                   
                 CACGGCTATGGCTGCACCACGCTGCCCGACGG 
               
               
                   
                   
                 CCACCGCGAGGAGGGCAAGTACCGCCACAACG 
               
               
                   
                   
                 TGCTGGTCAAGGACACCAAGCGCCGCATGCTG 
               
               
                   
                   
                 CAGCTCAAGAGCAACAAGGTCCGCCAGAAAGT 
               
               
                   
                   
                 GGAGCACAGTGTGGAGGGTGCCCAGCGCGCCG 
               
               
                   
                   
                 CTGCTATCGCGCGCCAGAAGGCCGAGATTGCC 
               
               
                   
                   
                 GCCTCCAGGACAAGCCACGCCAAGGCCAAAGC 
               
               
                   
                   
                 TGAGGCAGCGGAACAGGCCGCCCTGGCTGCCA 
               
               
                   
                   
                 ACCAGGAGTCCAACATTGCTCGCACTTTGGCCA 
               
               
                   
                   
                 GGGAGCTGGCTCCGGACTTCTACCAGCCAGGTC 
               
               
                   
                   
                 CGGAATATCAGAAGCGCCGGCTGCTGCAGGAG 
               
               
                   
                   
                 ATCCTGGAGAACTCGGAGAGCCTGCTGGAGCC 
               
               
                   
                   
                 CCCCGACCGGGGCGCCGGCGCAGCGGGCCTCC 
               
               
                   
                   
                 CACAGCCGCCCCGCGAGAGCCCGCAGCTGCAC 
               
               
                   
                   
                 GAGCGTGAGACCCCTCGGCCCGAGGGTGGCTC 
               
               
                   
                   
                 CCCGTCACCGGCCGGGACGCCCCCGCAGCCCA 
               
               
                   
                   
                 AGCGGCCCAGGCCCGGGGTGTCCAAGGACGGC 
               
               
                   
                   
                 CTGCTGAGCCCAGGCGCCTGGAACGGCGAGCC 
               
               
                   
                   
                 CAGCGGTGAGGGCAGCCGGTCAGTCACTCCGT 
               
               
                   
                   
                 CCGAGGGCGCGGGCCGCCGCAGCCCCGCGCGT 
               
               
                   
                   
                 CCAGCCACCGAGCGCATGGCCATCGAGGCTCT 
               
               
                   
                   
                 GCAGGCACCGCCTGCGCCGTCGCGGGAGCCGG 
               
               
                   
                   
                 AGGTGGCGCTTTACCAGGGCTACCACAGCTATG 
               
               
                   
                   
                 CTGTGCGC (SEQ ID NO: 227) 
               
               
                   
               
               
                 Human PLN 
                 MEKVQYLTRSAIRRASTIEMPQQ 
                 ATGGAGAAAGTCCAATACCTCACTCGCTCAGCT 
               
               
                   
                 ARQKLQNLFINFCLILICLLLICIIV 
                 ATAAGAAGAGCCTCAACCATTGAAATGCCTCA 
               
               
                   
                 MLL (SEQ ID NO: 230) 
                 ACAAGCACGTCAAAAGCTACAGAATCTATTTAT 
               
               
                   
                   
                 CAATTTCTGTCTCATCTTAATATGTCTCTTGCTG 
               
               
                   
                   
                 ATCTGTATCATCGTGATGCTTCTCTGA (SEQ ID 
               
               
                   
                   
                 NO: 229) 
               
               
                   
               
            
           
         
       
     
     Promoters and Enhancers 
     In some embodiments, the expression cassette of the disclosure comprises a promoter. The term “promoter” as used herein refers to a DNA sequence that directs the binding of RNA polymerase and thereby promotes RNA synthesis. Promoters and corresponding protein or polypeptide expression may be ubiquitous, meaning strongly active in a wide range of cells, tissues and species or cell-type specific, tissue-specific, or species specific. Examples of ubiquitous promoters include the CAG promoter and CMB promoter (Yue et al.  BioTeehniques  33:672-678 (2002)). Promoters may be “constitutive,” meaning continually active, or “inducible,” meaning the promoter can be activated or deactivated by the presence or absence of biotic or abiotic factors. Also included in the nucleic acid constructs or vectors of the invention are enhancer sequences that may or may not be contiguous with the promoter sequence. Enhancer sequences influence promoter-dependent gene expression and may be located in the 5′ or 3′ regions of the native gene. 
     Various promoters may be used. The promoter may be cell-type specific. Constitutive promoters are used in expression cassettes and can be, for example, the cytomegalovirus enhancer fused to the chicken β-actin promoter (CAG), simian virus 40 (SV40) promoter, and the herpes simplex virus thymidine kinase (HSV-TK) promoter (Damdindoij et al.  PLoS One.  9:e106472 (2014)). Other cell-type specific promoters may also be used. Cardiac cell specific promoters can be, for example, the MLC2v promoter (Phillips et al.  Hypertension  39:651-5 (2002)) and the cardiac Troponin-T (cTnT) promoter (Konkalmatt et al.  Circ Cardiovasc Imaging.  6:478-486 (2013)). The transgene polynucleotide sequence in an expression cassette can be, for example, an open reading frame encoding a protein. The ITRs in an expression cassette serve as markers used for viral packaging of the expression cassette (Clark et al.  Hum Gene Ther.  6:1329-41 (1995)). 
     Advantageously, the promoter, optionally in conjunction with an enhancer, enables expression of the polynucleotide encoding a polypeptide (e.g., a DWORF polypeptide), or functional variant thereof, in a target cell. 
     In some embodiments, the expression cassette comprises a single promoter. In some embodiments, the expression cassette comprises at least one promoter. In some embodiments, the expression cassette comprises two promoters. In some embodiments, the expression cassette comprises a ubiquitous promoter. In some embodiments, the expression cassette comprises an inducible promoter. In some embodiments, the expression cassette comprises a cell-type specific promoter. In some embodiments, the promoter specifically promotes expression of the polynucleotide encoding a polypeptide, or functional variant thereof, in a cardiac cell (e.g., a cardiomyocyte). In some embodiments, the promoter specifically promotes expression of the polynucleotide encoding the DWORF polypeptide, or functional variant thereof, in a cardiac cell. In some embodiments, the promoter specifically promotes expression of the polynucleotide encoding the DWORF polypeptide, or functional variant thereof, in a cardiomyocyte. Illustrative promoter and enhancer sequences are provided in Table 3. 
     in some embodiments, the promoter is a chicken cardiac troponin-T (cTnT or ccTnT) promoter. In some embodiments, the chicken cTnT promoter comprises a polynucleotide sequence that shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 11. In some embodiments, the chicken cTnT promoter comprises SEQ ID NO: 11. 
     In some embodiments, the promoter is a human cTnT promoter. In some embodiments, the promoter is a short human cTnT promoter. in some embodiments, the short human cTnT promoter comprises a polynucleotide sequence that shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 12. In some embodiments, the short human cTnT promoter comprises SEQ ID NO: 12. In some embodiments, the promoter is a long human cTnT promoter. In some embodiments, the long human cTnT promoter comprises a polynucleotide sequence that shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 13. In some embodiments, the long human cTnT promoter comprises SEQ ID NO: 13. 
     The expression cassette can include one or more enhancers. The term “enhancer” as used herein refers to a DNA sequence that directs the binding of transcriptional regulatory proteins (e.g., transcriptional machinery) and RNA polymerase, and thereby promotes RNA synthesis. The enhancer can be operably linked to a promoter and modulate the expression of a transgene operably linked to a promoter. The presence of an enhancer can modulate transgene expression by, for example, increasing expression or decreasing expression. An enhancer can modulate transgene expression by, for example, increasing expression levels in a desired cell type, for example, a cardiac cell. An enhancer can modulate transgene expression by, for example, decreasing expression levels in an “off-target” cell type, or a cell type in which expression is not desired. 
     In some embodiments, the expression cassette comprises a single enhancer. In some embodiments, the expression cassette comprises at least one enhancer. In some embodiments, the expression cassette comprises two enhancers. In some embodiments, the expression cassette comprises three enhancers. In some embodiments, the expression cassette comprises four enhancers. In some embodiments, the expression cassette comprises an enhancer that is operably linked to a promoter. For example, a ACTC1 cardiac enhancer can be linked to a human cTnT promoter. In some embodiments, the expression cassette comprises an enhancer that is operably linked to another enhancer. For example, a ACTC1 cardiac enhancer can be operably linked to an αMHC enhancer. In some embodiments, the expression cassette comprises an enhancer that is operably linked to a promoter and operably linked to another enhancer. 
     In some embodiments, the enhancer comprises an ACTC1 cardiac enhancer (ACTC1e). In some embodiments, the ACTC1 cardiac enhancer shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 78. In some embodiments, the ACTC1 cardiac enhancer comprises SEQ ID NO: 78. some embodiments, the enhancer comprises an αMHC enhancer (αMHCe). In some embodiments, the αMHC enhancer shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 79. In some embodiments, the αMHC enhancer comprises SEQ ID NO: 79. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Illustrative Promoter and Enhancer Sequences 
               
            
           
           
               
               
            
               
                 Promoter/ 
                   
               
               
                 Enhancer 
                   
               
               
                 Name 
                 Sequences 
               
               
                   
               
               
                 Chicken cTnT 
                 GGGATAAAAGCAGTCTGGGCTTTCACATGACAGCATCTGGGGCTGCGGCAGAGG 
               
               
                   
                 GTCGGGTCCGAAGCGCTGCCTTATCAGCGTCCCCAGCCCTGGGAGGTGACAGCTG 
               
               
                   
                 GCTGGCTTGTGTCAGCCCCTCGGGCACTCACGTATCTCCGTCCGACGGGTTTAAAA 
               
               
                   
                 TAGCAAAACTCTGAGGCCACACAATAGCTTGGGCTTATATGGGCTCCTGTGGGGG 
               
               
                   
                 AAGGGGGAGCACGGAGGGGGCCGGGGCCGCTGCTGCCAAAATAGCAGCTCACAA 
               
               
                   
                 GTGTTGCATTCCTCTCTGGGCGCCGGGCACATTCCTGCTGGCTCTGCCCGCCCCGG 
               
               
                   
                 GGTGGGCGCCGGGGGGACCTTAAAGCCTCTGCCCCCCAAGGAGCCCTTCCCAGAC 
               
               
                   
                 AGCCGCCGGCACCCACCGCTCCGTGGGA (SEQ ID NO: 11) 
               
               
                   
               
               
                 Short Human 
                 GTCATGGAGAAGACCCACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCA 
               
               
                 cTnT 
                 ACCTGCCTAAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTA 
               
               
                   
                 CCCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAG 
               
               
                   
                 ATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCC 
               
               
                   
                 TGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGATTC 
               
               
                   
                 TCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATCTGCTCTGGT 
               
               
                   
                 TTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGGCTTATATGGCGTGGGG 
               
               
                   
                 TACATGTTCCTGTAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCC 
               
               
                   
                 CACCCCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCCTCC 
               
               
                   
                 GCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATC 
               
               
                   
                 CTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACGCCTCCA  
               
               
                   
                 (SEQ ID NO: 12) 
               
               
                   
               
               
                 Long Human 
                 AGAGGACCCTTTCAAGGACATTAGTGGTGGAGGCAGCATAGTAGCTCCCAAGGCA 
               
               
                 cTnT 
                 GAGGGATTGAGAGAAGAGTTTGAGGACTGGGAAGGCGGGACACATGATTGGGTG 
               
               
                   
                 ATGGGAGAAGGGGGCAGAGAATAGCGAGATTGCTTTCTTTGCCCACGGAGAAAC 
               
               
                   
                 AGAGGAGTGTGGATCATGAATGGGCAAGATCTTTAAGTGCCAGGGGGGGTCATG 
               
               
                   
                 GAGGAGGGGAGGGCCTGCTCCAGAGGAGGACCATTCCTGCTTCAGAGCCAAGCA 
               
               
                   
                 GGACCTAGGCTGTGAAGATTCGGAGAAAGAGATGGAGGGGAGAGTCAGCTCAGC 
               
               
                   
                 TGCTTACTGGCTTGCTTTCCTCCTGTCTCTTTCATTTTCATAATCTACCAAACCCTG 
               
               
                   
                 CAATGGGCCAGCCTTGAACATACAAGTGCATGTGCATGGTCAGACACAGGCAAGC 
               
               
                   
                 AAGCAAGACCCCTAGGCCTGACCTATGCATCTGCAATCTAGTAGGTTTAGCAGAT 
               
               
                   
                 CATAGCCCCGCACTGCTTGATTTTAAAGCCGTTAGGGGATGACCTTTGACAGTCCG 
               
               
                   
                 CATCACCCCTCTCACACAACGAGCGCCTGTTCAAGGTTCTTGACTGGAAGTTCTAC 
               
               
                   
                 CTTGTATCTGGCCTCCTGTAGCAGTTTCAGTCCATTCCCTGTGAGGAGGGTGTGCC 
               
               
                   
                 ACATGGCTTTGGGGGTCATGGAGAAGACCCACCTTGCAGATGTCCTCACTGGGGC 
               
               
                   
                 TGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCT 
               
               
                   
                 GGAAGATGTCTTTACCCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGC 
               
               
                   
                 CCTCTGCCTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCT 
               
               
                   
                 TCTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCT 
               
               
                   
                 GCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTG 
               
               
                   
                 CATATCTGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGGCT 
               
               
                   
                 TATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTGCCAAAATAG 
               
               
                   
                 CAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGC 
               
               
                   
                 ACATTCCTCCCTCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAA 
               
               
                   
                 AGCCCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACGCCTCC 
               
               
                   
                 AGGATCTGTCGGCAGCTGCTGTTCTGAGGTAAGGCTCGGGCAGGGCTCTGGGGAA 
               
               
                   
                 GAGGAGAGCAGAGAATGGACGGGGAGATGTGAGGGTCTTGGGCCCTGGCATATT 
               
               
                   
                 TACCCAGAGTCTGCCTGTGTCCGCAGAAGTCCATGGCCCCTCCTGGTGGAGGCCA 
               
               
                   
                 CACTTCAGAGGACAGGTTGCCAGGTCTGGGCTCCAAGATTGGTACAATAGAGCAG 
               
               
                   
                 AGAGA (SEQ ID NO: 13) 
               
               
                   
               
               
                 ACTC1 cardiac 
                 AACTGGCCTGCCCGAGACCAAACGTGCGGAACGTAGTTAAGTGTTAGAGGTAGG 
               
               
                 enhancer 
                 ATTTGAAGCCTGTCGATCATTCTGATTCTCCTTTTCTCTACGTCTGCTTCCTGTCAA 
               
               
                 (ACTC1e) 
                 TGGGCATCCTCACTGTCAAATGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGG 
               
               
                   
                 CAGGCCTCTCCCCAGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCA 
               
               
                   
                 TCCCAAACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCCCTG 
               
               
                   
                 AAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTCTAGACAGAGA 
               
               
                   
                 TGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACTGAAGGAAAAGCACAGC 
               
               
                   
                 ATTAGAAGTCCAAGCA (SEQ ID NO: 78) 
               
               
                   
               
               
                 αMHC cardiac 
                 CCTTCAGATTAAAAATAACTAAGGTAAGGGCCATGTGGGTAGGGGAGGTGGTGTG 
               
               
                 enhancer 
                 AGACGGTCCTGTCTCTCCTCTATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTG 
               
               
                 (αMHCe) 
                 CCCAAGGACTAAAAAAAGGCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTT 
               
               
                   
                 CATGGGCAAACCTCAGGGCTGCTGTC (SEQ ID NO: 79) 
               
               
                   
               
            
           
         
       
     
     Introns 
     The expression cassette can include an intron sequence, for example, a synthetic or chimeric introit sequence. The intron sequence can be used to adjust the length (i.e., size) of the expression cassette for improving recombinant AAV packaging. The intron sequence can be used to improve the efficiency of transgene expression (i.e., mRNA production or transcription) in a host cell containing the expression cassette. In some embodiments, the expression cassette comprises an intron. In some embodiments, the intron comprises the CMV intron (CMVint). In some embodiments, the CMV intron shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 80. In some embodiments, the CMV intron comprises SEQ ID NO: 80. In some embodiments, the intron comprises a chimeric intron. In some embodiments, the chimeric intron shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 81. In some embodiments, the chimeric intron comprises SEQ ID NO: 81. 
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 Illustrative Intron Sequences 
               
            
           
           
               
               
               
            
               
                   
                 Intron 
                 Intron Sequence 
               
               
                   
               
               
                   
                 CMV 
                 GTAAGTACCGCCTATAGACTCTATAGGCACACCCC 
               
               
                   
                 intron 
                 TTTGGCTCTTATGCATGCTGACAGACTAACAGACT 
               
               
                   
                   
                 GTTCCTTTCCTGGGTCTTTTCTGCAG 
               
               
                   
                   
                 (SEQ ID NO: 80) 
               
               
                   
               
               
                   
                 Chimeric 
                 GTAAGTATCAAGGTTACAAGACAGGTTTAAGGAGA 
               
               
                   
                 Intron 
                 CCAATAGAAACTGGGCTTGTCGAGACAGAGAAGAC 
               
               
                   
                 (Chimint) 
                 TCTTGCGTTTCTGATAGGCACCTATTGGTCTTACT 
               
               
                   
                   
                 GACATCCACTTTGCCTTTCTCTCCACAG  
               
               
                   
                   
                 (SEQ ID NO: 81) 
               
               
                   
               
            
           
         
       
     
     WPRE Sequences and Other Post-Transcriptional Elements 
     In some embodiments, the expression cassette comprises a posttranscriptional regulatory element. 
     In some embodiments, the expression cassette comprises a woodchuck hepatitis virus post-transcriptional element (WPRE). The WPRE sequence can be inserted, for example, proximal to on the 3′ end of a transgene in a viral vector to, for example, optimize gene expression in a viral vector (Lee et al.  Exp Physiol.  90:33-37 (2005)). In some embodiments, the WPRE comprises a polynucleotide sequence that shares at least 90%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 26. In some embodiments, the WPRE comprises SEQ ID NO: 26. 
     
       
         
           
               
             
               
                 TABLE 4 
               
               
                   
               
               
                 Illustrative WPRE Sequence 
               
               
                 WPRE Sequence 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 TCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTA 
               
               
                 TGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCA 
               
               
                 TGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTG 
               
               
                 GTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGT 
               
               
                 GGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCAC 
               
               
                 CACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCAC 
               
               
                 GGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCT 
               
               
                 GTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCC 
               
               
                 TTGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTG 
               
               
                 CTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCT 
               
               
                 GCCGGCTCTGCGGCCTCTTCCGCGTCTTCG (SEQ ID NO: 26) 
               
               
                   
               
            
           
         
       
     
     Poly Adenylation Sequences 
     In some embodiments, the expression cassette comprises a poly(A) signal sequence. In some embodiments, the poly(A) signal is a BGH poly(A) sequence. In some embodiments, the BGH poly(A) signal sequence comprises the polynucleotide sequence that shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 27. In some embodiments, the poly(A) signal is an SV40 poly(A) signal. In some embodiments, the SV40 poly(A) signal sequence comprises the polynucleotide sequence that shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 28. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Illustrative Poly(A) Sequences 
               
            
           
           
               
               
            
               
                 Poly(A) 
                   
               
               
                 Sequence 
                 Sequence 
               
               
                   
               
               
                 BGH 
                 GCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTT 
               
               
                   
                 GCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCAC 
               
               
                   
                 TCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCG 
               
               
                   
                 CATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGG 
               
               
                   
                 TGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAG 
               
               
                   
                 CAGGCATGCTGGGGA (SEQ ID NO: 27) 
               
               
                   
               
               
                 SV40 
                 GATCCAGACATGATAAGATACATTGATGAGTTTGGACAAA 
               
               
                   
                 CCACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGA 
               
               
                   
                 AATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGC 
               
               
                   
                 TGCAATAAACAAGT (SEQ ID NO: 28) 
               
               
                   
               
            
           
         
       
     
     Inverted Terminal Repeat Sequences 
     In some embodiments, the expression cassette is flanked by AAV inverted terminal repeats (ITRs). In some embodiments, the ITRs comprise the polynucleotide sequence that shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 14 and/or SEQ ID NO: 15. 
     
       
         
           
               
             
               
                 TABLE 6 
               
               
                   
               
               
                 Illustrative ITR Sequences 
               
               
                 ITR Sequences 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTC 
               
               
                 GGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGA 
               
               
                 GGGAGTGGCCAACTCCATCACTAGGGGTTCCT (SEQ ID NO: 14) 
               
               
                   
               
               
                 AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTC 
               
               
                 GCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCC 
               
               
                 CGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID NO: 15) 
               
               
                   
               
            
           
         
       
     
     Illustrative Expression Cassettes 
     The disclosure provides expression cassettes comprising a polynucleotide comprising a 5′ to 3′ arrangement (sometimes referred to as an orientation) of elements. In some embodiments, the elements comprise one or more promoters; optionally one or more enhancers; optionally one or more introns; one or more transgenes; optionally one or more WPRE sequences; and optionally one or more polyadenylation sequences (p(A)). Illustrative order of the elements in the polynucleotide are shown in  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  and Table 1. Illustrative orientations of the elements on the polynucleotide are also shown in  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  and Table 1. In some embodiments, the 5′ to 3′ arrangement of elements is selected from: 
     5′-promoter-transgene-WPRE-p(A)-3′; 
     5′-promoter-intron-transg,ene-WPRE-p(A)-3′; 
     5′-promoter-transgene-WPRE-p(A)-promoter-transgene-WPRE-p(A); 
     5′-enhancer-promoter-transgene-WPRE-p(A)-3′; 
     5′-enhancer-promoter-intron-transgene-WPRE-p(A)-3′; 
     5′-enhancer-enhancer-promoter-transgene-WPRE-p(A)-3′; 
     5′-enhancer-enhancer-promoter-intron-transgene-WPRE-p(A)-3′; 
     5′-enhancer-promoter-intron-transgene-WPRE-p(A)-p(A)-transgene-intron-promoter-enhancer-3′; 
     5′-enhancer-promoter-intron-transgene-WPRE-p(A)-enhancer-promoter-intron-transgene-p(A)-3′; 
     5′-p(A)-WPRE-transgene-intron-promoter-enhancer-enhancer-promoter-intron-transgene-p(A)-3′; 
     5′-promoter-intron-transgene-WPRE-p(A)-p(A)-transgene-intron-promoter-3′; 
     5′-promoter-intron-transgene-WPRE-p(A)-promoter-intron-transgene-p(A)-3′; and 
     5′-p(A)-WPRE-transgene-intron-promoter-promoter-intron-transgene-p(A)-3′. 
     In some embodiments, the expression cassettes described herein achieve an increased expression level of the transgene compared to a second expression cassette comprising a polynucleotide having an arrangement of elements from 5′ to 3′ comprising: 5′-promoter-transgene-WPRE-p(A)-3′. In some embodiments, the expression level is increased between about 1.5-fold and about 150-fold compared the second expression cassette. 
     In some embodiments, the expression cassettes provided herein comprise the following elements (where the elements can be those described herein, e.g., the sequences of which are provided herein): 
     5′-promoter-transgene-WPRE-p(A)-3′; 
     5′-promoter-intron-transgene-WPRE-p(A)-3′; 
     5′-promoter-transgene-WPRE-p(A)-promoter-transgene-WPRE-p(A); 
     5′-enhancer-promoter-transgene-WPRE-p(A)-3′; 
     5′-enhancer-promoter-intron-transgene-WPRE-p(A)-3′; 
     5′-enhancer-enhancer-promoter-transgene-WPRE-p(A)-3′; 
     5′-enhancer-enhancer-promoter-intron-transgene-WPRE-p(A)-3′; 
     5′-enhancer-promoter-intron-transgene-WPRE-p(A)-p(A)-transgene-intron-promoter-enhancer-3′; 
     5′-enhancer-promoter-intron-transgene-WPRE-p(A)-enhancer-promoter-intron-transgene-p(A)-3′; 
     5′-p(A)-WPRE-transgene-intron-promoter-enhancer-enhancer-promoter-intron-transgene-p(A)-3′; 
     5′-promoter-intron-transgene-WPRE-p(A)-p(A)-transgene-intron-promoter-3′; 
     5′-promoter-intron-transgene-WPRE-p(A)-promoter-intron-transgene-p(A)-3′; or 
     5′-p(A)-WPRE-transgene-intron-promoter-promoter-intron-transgene-p(A)-3′. 
     In the expression cassettes described herein (such as those listed above), the orientation of the promoter, enhancer, transgene and poly(A) elements can be forward or reverse (e.g., in cases where there are more than one promoters, one promoter, optionally enhancer, and operably linked transgene can be oriented in a forward direction, and another promoter, optionally enhancer, and operably linked transgene can be oriented in a reverse direction). 
     In some embodiments, the expression cassettes provided herein comprise the following elements: 
     5′-cardiac-specific promoter-transgene-WPRE-p(A)-3′; 
     5′-cardiac-specific promoter-intron (e.g., chimeric intron)-transgene-WPRE-p(A)-3′; 
     5′-cardiac-specific promoter-transgene-WPRE-p(A)-promoter-transgene-WPRE-p(A), where both promoters and transgene sequences are in the same, forward orientation; 
     5′-cardiac-specific promoter-transgene-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-cardiac-specific promoter-intron (e.g., CMV intron)-transgene-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-enhancer (e.g., ACTC1e)-cardiac-specific promoter-transgene-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-enhancer (e.g., αMHCe)-cardiac-specific promoter-transgene-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-enhancer (e.g., ACTC1e)-cardiac-specific promoter-intron (e.g., CMV intron)-transgene-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-enhancer (e.g., αMHCe)-cardiac-specific promoter-intron (e.g., CMV intron)-transgene-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-enhancer (e.g., ACTC1e)-enhancer (e.g., αMHCe)-cardiac-specific promoter-transgene-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-enhancer (e.g., αMHCe)-enhancer (e.g, ACTC1e)-cardiac-specific promoter-transgene-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-enhancer (e.g., ACTC1e)-enhancer (e.g., αMHCe)-cardiac-specific promoter-intron (e.g., CMV intron)-transgene-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-enhancer (e.g., αMHCe)-enhancer (e.g., ACTC1e)-cardiac-specific promoter-intron (e.g., CMV intron)-transgene-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-cardiac-specific promoter-transgene with a codon-optimized polynucleotide sequence-WPRE-p(A) (e.g., bGHpA)-3′; 
     5′-enhancer (e.g., αMHCe)-cardiac-specific promoter-intron (e.g., CMV intron)-transgene-WPRE-p(A) (e.g., bGHpA)-p(A) (e,g., SV40pA)-transgene (e.g., with a codon-optimized polynucleotide sequence)-intron (e.g., chimeric intron)-cardiac-specific promoter-enhancer (e.g., ACTC1e)-3′, optionally wherein the first in order transgene and the promoter/enhancer sequences operably linked thereto are in a forward orientation, and the second in order transgene and the promoter/enhancer sequences operably linked thereto are in a reverse orientation; 
     5′-enhancer (e.g., αMHCe)-cardiac-specific promoter-intron (e.g., CMV intron)-transgene-WPRE-p(A) (e.g., bGHpA)-enhancer (e.g., ACTC1e)-cardiac-specific promoter-intron (e.g., chimeric intron)-transgene (e.g., with a codon-optimized polynucleotide sequence)-p(A) (e.g., SV40pA)-3′, optionally wherein both the first and the second in order transgenes and the promoter/enhancer sequences operably linked thereto are in a forward orientation; 
     5′-p(A) (e.g., bGHpA)-WPRE-transgene-intron (e.g., CMV intron)-cardiac-specific promoter-enhancer (e.g., αMHCe)-enhancer (e.g., ACTC1e)-cardiac-specific promoter-intron (e.g., chimeric intron)-transgene (e.g., with a codon-optimized polynucleotide sequence)-p(A) (e.g., SV40pA)-3′, optionally wherein the first in order transgene and the promoter/enhancer sequences operably linked thereto are in a reverse orientation, and the second in order transgene and the promoter/enhancer sequences operably linked thereto are in a forward orientation; 
     5′-cardiac-specific promoter-intron (e.g., CMV intron)-transgene-WPRE-p(A) (e.g., bGHpA)-p(A) (e.g., SV40pA)-transgene (e.g., with a codon-optimized polynucleotide sequence)-intron (e.g., chimeric intron)-cardiac-specific promoter-3′, optionally wherein the first in order transgene and the promoter/enhancer sequences operably linked thereto are in a forward orientation, and the second in order transgene and the promoter/enhancer sequences operably linked thereto are in a reverse orientation; 
     5′-cardiac-specific promoter-intron (e.g., CMV intron)-transgene-WPRE-p(A) (e.g., bGHpA)-cardiac-specific promoter-intron (e.g., chimeric intron)-transgene (e.g., with a codon-optimized polynucleotide sequence)-p(A) SV40pA)-3′, optionally wherein both the first and the second in order transgenes and the promoter;/enhancer sequences operably linked thereto are in a forward orientation; or 
     5′-p(A) (e.g., bGHpA)-WPRE-transgene-intron (e.g., CMV intron)-cardiac-specific promoter-cardiac-specific promoter-intron (e.g., chimeric intron)-transgene (e.g., with a codon-optimized polynucleotide sequence)-p(A) (e.g., SV40pA)-3′, optionally wherein the first in order transgene and the promoter/enhancer sequences operably linked thereto are in a reverse orientation, and the second in order transgene and the promoter/enhancer sequences operably linked thereto are in a forward orientation. 
     In the expression cassettes described herein (such as those listed above), the cardiac-specific promoter can be a short human cTnT promoter (such as hcTnTp) or chicken cTnT promoter (such as ccTnTp). The more specific examples of the expression cassettes described above can be found in, e.g.,  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  and Table 1. 
     In some embodiments, the expression cassettes described herein enable an increased expression level of the transgene compared to a second expression cassette comprising a polynucleotide having an arrangement of elements from 5′ to 3′ comprising: 5′-promoter-transgene-WPRE-p(A)-3′. In some embodiments, the expression level is increased between about 1.5-fold and about 150-fold compared the second expression cassette. 
     In some embodiments, one or more (e.g., one, two, three or four) elements of the expression cassettes described herein can he omitted. 
     In some embodiments, one or more (e.g., one, two, three or four) elements of the expression cassettes described herein can be replaced by other elements, such as functionally equivalent elements. 
     In some embodiments of the expression cassettes provided herein, the WPRE element is replaced by any other post-transcriptional regulatory element known in the art. In some embodiments, the expression cassettes provided herein comprise any post-transcriptional regulatory element known in the art. In some embodiments, the expression cassettes provided herein do not comprise a post-transcriptional regulatory element (e.g., do not comprise the WPRE element). In some embodiments, the expression cassettes provided herein comprise WPRE. 
     In some embodiments of the expression cassettes provided herein, the bGHpA and/or SV40pA poly(A) element is replaced by any other poly(A) element known in the art. In some embodiments, the expression cassettes provided herein comprise any poly(A) element known in the art. In some embodiments, the expression cassettes provided herein do not comprise a poly(A) element. In some embodiments, the expression cassettes provided herein do not comprise bGHpA. In some embodiments, the expression cassettes provided herein do not comprise SV40pA. In some embodiments, the expression cassettes provided herein do not comprise bGHpA or SV40pA. In some embodiments, the expression cassettes provided herein comprise one or both of bGHpA and SV40pA. 
     In some embodiments of the expression cassettes provided herein, the CMV intron and/or chimeric intron element is replaced by any other intron element known in the art. In some embodiments, the expression cassettes provided herein comprise any intron element known in the art. In some embodiments, the expression cassettes provided herein do not comprise an intron. In some embodiments, the expression cassettes provided herein do not comprise a CMV intron. In some embodiments, the expression cassettes provided herein do not comprise a chimeric intron (e.g., do not comprise Chim int). In some embodiments, the expression cassettes provided herein do not comprise CMV intron or Chim int. In some embodiments, the expression cassettes provided herein comprise one or both of CMV intron and Chim int. 
     It should be understood that the illustrative orientations of the expression cassette can include flanking inverted terminal repeat (ITR) sequences on the 5′ and 3′ ends of the expression cassette. It should be understood that the ITR sequences can be optional. In some embodiments, the expression cassettes described herein do not include the ITR sequences (e.g., non-AAV, such as DNA plasmid-based, expression cassettes). 
     Operably linked elements, such as those in the illustrative orientations above, can be on one or both strands of the polynucleotide. 
     In some embodiments, the expression cassette comprises one copy of a sequence encoding a polypeptide (i.e., one copy of a transgene). In some embodiments, the expression cassette comprises two copies of a sequence encoding a polypeptide (i.e., two copies of a transgene). In some embodiments, where the expression cassette comprises two copies of a sequence encoding a polypeptide, the two “copies” are not identical. While not being bound by any theory, using two sequences encoding a polypeptide that are not identical may prevent DNA recombination within the vector. In some embodiments, the expression cassette comprises one copy that has the original DNA sequence encoding a polypeptide and one copy that has a codon optimized DNA sequence encoding the polypeptide. In some embodiments, where the expression cassette comprises two copies of a sequence encoding a polypeptide, the two copies are identical. 
     In some embodiments, the expression cassette comprises one or more promoters described herein (with or without one or more enhancers described herein) driving one or more copies of a transgene (such as any transgene described herein). In some embodiments, the expression cassette does not comprise an enhancer (e.g., αMHCe and/or ACTC1e). In some embodiments, the expression cassette comprises one or more enhancers such as cardiac-specific enhancers (e.g., αMHCe and/or ACTC1e), In some embodiments, the expression cassette comprises αMHCe enhancer (and, optionally, does not comprise ACTC1e enhancer). In some embodiments, the expression cassette comprises ACTC1e enhancer (and, optionally, does not comprise αMHCe enhancer). In some embodiments, the expression cassette comprises at least two enhancers in the order of first αMHCe and then ACTC1e. In some embodiments, the expression cassette comprises at least two enhancers in the order of first ACTC1e and then αMHCe. In some embodiments, the expression cassette comprises an intron element, e.g., a CMV intron element and/or a chimeric intron (such as Chim int described herein). In some embodiments, the expression cassette comprises an intron element but does not comprise an enhancer. In some embodiments, the expression cassette comprises an intron element (e.g., CMV intron and/or a chimeric intron) and further comprises an enhancer (e.g., αMHCe and/or ACTC1e). In some embodiments, the expression cassette comprises a transgene with a codon-optimized polynucleotide sequence. In some embodiments, the expression cassette comprises a transgene with a codon-optimized polynucleotide sequence but does not comprise an enhancer. In some embodiments, the expression cassette comprises a transgene with a codon-optimized polynucleotide sequence and further comprises an enhancer (e.g., αMHCe and/or ACTC1e). In some embodiments, the expression cassette comprises one or more promoters described herein and one, two or more enhancers described herein (e.g., comprises an αMHCe and/or ACTC1e enhancer) driving the expression of one or more copies of a transgene (without or without CMV intron or chimeric intron elements). In some embodiments, the promoter is a cardiac-specific promoter, e.g., a human cTnT promoter (such as a short human promoter, hcTnTp) and/or a chicken cTnT promoter (such as ccTnTp). In some of the embodiments, the enhancer is a cardiac-specific enhancer, e.g., αMHCe and/or ACTC1e. In some embodiments, two or more cardiac-specific enhancers are used, where the two or more of the enhancers can be the same or different (e.g., both or all αMHCe, both or all ACTC1e, or at least one αMHCe and at least one ACTC1e). In some embodiments, two cardiac-specific enhancers are used, where the two enhancers can be the same or different (e.g., both αMHCe, both ACTC1e, or one αMHCe and one ACTC1e). In some embodiments, the transgene comprises a non-codon-optimized polynucleotide sequence encoding a gene product. In some embodiments, the order of the elements is as shown in any of the expression cassettes depicted in  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  and Table 1. For example, (i) the order of the promoter and transgene elements can be as shown in  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  or Table 1, (ii) the order of promoter, enhancer and transgene elements can be as shown in  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  or Table 1, (iii) the order of promoter, transgene, WPRE and poly(A) elements can be as shown in  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  or Table 1, optionally with or without enhancer elements being in the same order as shown in  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  or Table 1, or (iv) the order of promoter, transgene, WPRE, poly(A), CMV intron (such as CMVint) elements can be as shown in  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  or Table 1, optionally with or without enhancer elements being in the same order as shown in  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  or Table 1. In some embodiments, the orientation of any of the elements is as shown in any of the expression cassettes depicted in  FIG.  1   ,  FIG.  7 A ,  FIG.  7 B ,  FIG.  7 C  and Table 1. The sequences of individual expression cassette elements discussed herein (such as promoters, enhancers, transgenes, WPRE, poly(A), CMV intron and chimeric intron) can be any of the sequences of such elements provided herein or any sequences with at least, e.g., 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% sequence identity thereto. 
     In some embodiments, the expression cassette comprises one promoter described herein (with or without one or more enhancers described herein) driving one copy of a transgene (such as any transgene described herein). In some embodiments, the expression cassette comprises one promoter described herein, without any enhancer (e.g., without any enhancer described herein, e.g., without αMHCe and/or without ACTC1e) driving one copy of a transgene, optionally, such an expression cassette comprises an intron element, e.g, a CMV intron element and/or a chimeric intron (such as Chim int described herein), and/or comprises a transgene with a codon-optimized polynucleotide sequence. In some embodiments, the expression cassette comprises one promoter described herein, without any enhancer (e.g., without any enhancer described herein, e.g., without αMHCe and/or without ACTC1e) driving one copy of a transgene, and further comprises a CMV intron and/or a chimeric intron (such as Chim int). In some embodiments, the expression cassette comprises one promoter described herein, without any enhancer (e.g., without any enhancer described herein, e.g., without αMHCe and/or without ACTC1e) driving one copy of a transgene, and further comprises a CMV intron. In some embodiments, the expression cassette comprises one promoter described herein, without any enhancer (e.g., without any enhancer described herein, e.g., without αMHCe and/or without ACTC1e) driving one copy of a transgene, wherein the transgene comprises a codon-optimized polynucleotide sequence. In some embodiments, the expression cassette comprises one promoter described herein and one, two or more enhancers described herein (e.g., comprises an αMHCe and/or ACTC1e enhancer) driving the expression of one copy of a transgene. In some embodiments, the expression cassette comprises one promoter described herein and one enhancer described herein (e.g., αMHCe or ACTC1e enhancer) driving the expression of one copy of a transgene. In some embodiments, the expression cassette comprises one promoter described herein and two enhancers described herein (e.g., both αMHCe, both ACTC1e, or one αMHCe and one ACTC1e) operably linked to one copy of a transgene. In some embodiments, the promoter is a cardiac-specific promoter, e.g., a human cTnT promoter (such as a short human promoter, hcTnTp) and/or a chicken cTnT promoter (such as ccTnTp). In some of the embodiments where one or more enhancers are used, the enhancer is a cardiac-specific enhancer, e.g., αMHCe and/or ACTC1e. In some embodiments, two or more cardiac-specific enhancers are used, where the two or more of the enhancers can be the same or different (e.g., both or all αMHCe, both or all ACTC1e, or at least one αMHCe and at least one ACTC1e). In some embodiments, two cardiac-specific enhancers are used, where the two enhancers can be the same or different (e.g., both αMHCe, both ACTC1e, or one αMHCe and one ACTC1e). In some embodiments, the expression cassette comprises at least two enhancers in the order of first αMHCe and then ACTC1e. In some embodiments, the expression cassette comprises at least two enhancers in the order of first ACTC1e and then αMHCe. In some embodiments, the transgene comprises a non-codon-optimized polynucleotide sequence encoding a gene product. In some embodiments, the transgene comprises a codon-optimized polynucleotide sequence encoding the gene product. In some embodiments, one or more intron elements are also used in addition to promoter and enhancer elements. In some embodiments, a CMV intron element is used. In some embodiments, a chimeric intron element (Chim int) is used. In some embodiments, both a CMV intron and a chimeric intron (Chim int) are used. In some embodiments where one promoter is used, the order of the elements is as shown in any of the expression cassettes depicted in  FIG.  7 B . For example, (i) the order of the promoter and transgene elements can be as shown in  FIG.  7 B , (ii) the order of promoter, enhancer and transgene elements can be as shown in  FIG.  7 B , (iii) the order of promoter, transgene, WPRE and poly(A) elements can be as shown in  FIG.  7 B , optionally with or without enhancer elements being in the same order as shown in  FIG.  7 B , or (iv) the order of promoter, transgene, WPRE, poly(A), CMV intron (such as CMVint) elements can be as shown in  FIG.  7 B , optionally with or without enhancer elements being in the same order as shown in  FIG.  7 B . In some embodiments where one promoter is used, the orientation of any of the elements is as shown in any of the expression cassettes depicted in  FIG.  7 B . In some embodiments, the orientation of the elements is forward orientation. In some embodiments, the orientation of the elements is reverse orientation. The sequences of individual expression cassette elements discussed herein (such as promoters, enhancers, transgenes, WPRE, poly(A), CMV intron and chimeric intron) can be any of the sequences of such elements provided herein or any sequences with at least, e.g., 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% sequence identity thereto. 
     In some embodiments, the expression cassette comprises two promoters described herein (with or without one or more enhancers described herein) driving the expression of two copies of a transgene (such as any transgene described herein). In some embodiments, the expression cassette comprises two promoters described herein (with or without one or more enhancers described herein) each promoter operably linked to one copy of a transgene (such as any transgene described herein). In some embodiments, the expression cassette comprises two promoters described herein, without any enhancer (e.g., without any enhancer described herein, e.g., without αMHCe and/or without ACTC1e) driving the expression of two copies of a transgene. In some embodiments, the expression cassette comprises two promoters described herein and one, two or more enhancers described herein (e.g., comprising an αMHCe and/or ACTC1e enhancer) driving the expression of two copies of a transgene. In some embodiments, the expression cassette comprises two promoters described herein and two enhancers described herein (e.g., comprising an αMHCe and/or ACTC1e enhancer) operably linked to two copies of a transgene, where each transgene is operably linked to one promoter and one enhancer. In some embodiments, the promoter is a cardiac-specific promoter, e.g., a human cTnT promoter (such as a short human promoter, hcTnTp) and/or a chicken cTnT promoter (such as caTnTp). In the embodiments where two promoters are used, the two promoters can be the same or different. In some embodiments, where the two promoters drive the expression of two copies of a transgene (each promoter driving expression of one copy of the transgene), both promoters can be cardiac-specific promoters, either the same cardiac-specific promoters or different from each other. In some embodiments, both promoters can be human cTnT promoters (e.g., both can be a short human promoter, hcTnTp). In some embodiments, both promoters can be chicken cTnT promoters (such as ccTnT). In some embodiments, the two promoters are different, e.g., one is a human cTnT promoter (such as a short human cTnT promoter, hcTnTp) and one is a chicken cTnTpromoter (such as ccTnT). In some embodiments where two promoters and two transgenes are used, the two transgenes can be the same or different (such as the same or different variants of the same transgene). For example, the first copy of the transgene can be a non-codon-optimized polynucleotide sequence encoding a gene product, and the second copy of the transgene can be a codon-optimized polynucleotide sequence encoding the gene product. In some embodiments, both copies of the transgene used in an expression cassette are the same. In some of the embodiments where one or more enhancers are used, the enhancer is a cardiac-specific enhancer, e.g., αMHCe and/or ACTC1e. In some embodiments, two or more cardiac-specific enhancers are used, where the two or more of the enhancers can be the same or different (e.g., both or all αMHCe, both or all ACTC1e, or at least one αMHCe and at least one ACTC1e). In some embodiments, two cardiac-specific enhancers are used, where the two enhancers can be the same or different (e.g., both αMHCe, both ACTC1e, or one αMHCe and one ACTC1e). In some embodiments where two promoters are used, two cardiac-specific enhancers operably linked to the transgene are used as well, optionally wherein one enhancer is αMHCe and another is ACTC1e. In some embodiments, the expression cassette comprises at least two enhancers in the order of first αMHCe and then ACTC1e. In some embodiments, the expression cassette comprises at least two enhancers in the order of first ACTC1e and then αMHCe. In some embodiments where two promoters are used, one or more intron elements are also used. In some embodiments where two promoters are used, a CMV intron element is also used. In some embodiments where two promoters are used, a chimeric intron element (Chim int) is also used. In some embodiments where two promoters are used, a CMV intron and a chimeric intron (Chim int) are used. In some embodiments where two promoters are used, the order of the elements is as shown in any of the expression cassettes depicted in  FIG.  7 C . For example, (i) the order of the promoter and transgene elements can be as shown in  FIG.  7 C , (ii) the order of promoter, enhancer and transgene elements can be as shown in  FIG.  7 C , (iii) the order of promoter, transgene, WPRE and poly(A) elements can be as shown in  FIG.  7 C , optionally with or without enhancer elements being in the same order as shown in  FIG.  7 C , or (iv) the order of promoter, transgene, WPRE, poly(A), CMV intron (such as CMVint) and chimeric intron (such as Chim int) elements can be as shown in  FIG.  7 C , optionally with or without enhancer elements being in the same order as shown in  FIG.  7 C . In some embodiments where two promoters are used, the first promoter and the associated transgene (and, optionally an enhancer) are oriented in a forward 5′ to 3′ direction, and the second promoter and the associated transgene and, optionally an enhancer) are oriented in a reverse direction. In some embodiments where two promoters are used, the first promoter and the associated transgene (and, optionally an enhancer) are oriented in reverse relative to 5′ to 3′ direction, and the second promoter and the associated transgene (and, optionally an enhancer) are oriented in a forward direction. In some embodiments where two promoters are used, both promoters and the associated transgenes (and, optionally an enhancer) are oriented in a forward 5′ to 3′ direction. In some embodiments where two promoters are used, both promoters and the associated transgenes (and, optionally an enhancer) are oriented in reverse relative to the 5′ to 3′ direction. In some embodiments where two promoters are used, the orientation of any of the elements (such forward or reverse orientation in 5′ to 3′ direction) is as shown in any of the expression cassettes depicted in  FIG.  7 C . In some embodiments where two promoters are used, the orientation of promoters, enhancers if any, transgenes, WPRE, poly(A), CMV intron and chimeric intron elements (such forward or reverse orientation in 5′ to 3′ direction) is as shown in any of the expression cassettes depicted in  FIG.  7 C . The sequences of individual expression cassette elements discussed herein (such as promoters, enhancers, transgenes, WPRE, poly(A), CMV intron and chimeric intron) can be any of the sequences of such elements provided herein or any sequences with at least, e.g., 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% sequence identity thereto. 
     Expression cassette sequences of the disclosure can be found, without limitation, in Table 1. In some embodiments, the expression cassette comprises about 3.2 kilobases (kb), 3.3 kb, 3.4 kb, 3.5 kb, 3.6 kb, 3.7 kb, or less. In some embodiments, the expression cassette comprises about 1.9 kb, 2.1 kb, 2.2 kb, 2.3 kb, 2.4 kb, 2.5 kb, 2.6 kb, 2.7 kb, 2.8 kb, 2.9 kb, 3.0 kb, 3.1 kb, 3.2 kb, or more. 
     In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NOs: 20-24 and SEQ ID NOs: 45-63. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NOs: 64-75. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 61. In some embodiments, the expression cassette comprises SEQ ID NO: 61. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 62. In some embodiments, the expression cassette comprises SEQ ID NO: 62. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 63. In some embodiments, the expression cassette comprises SEQ ID NO: 63. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 49. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 51. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 55. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 56. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 57. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 58. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 59. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 60. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 67. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%,98%, 99%, or 100% identity to SEQ ID NO: 69. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 74. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 75. In some of these embodiments, the sequence encoding DWORF (the DWORF open reading frame) can be replaced by a sequence encoding another polypeptide described herein, and the sequence identity referenced above does not take into account the part of the polynucleotide sequence encoding DWORF (the DWORF open reading frame). 
     In some embodiments, the transgene in the expression cassette encodes a polypeptide for use in treating or preventing a heart disease or disorder. In some embodiments, the transgene in the expression cassette encodes a polypeptide selected from: DWORF, junctophilin (e.g., JPH2), BAG family molecular chaperone regulator 3 (BAG-3), alpha-crystallin B chain (CRYAB), LMNA (such as Lamin A and Lamin C isoforms), troponin I type 3 (TNNI3), phospholamban (PLN), lysosomal-associated membrane protein 2 (LAMP2, such as LAMP2a, LAMP2b and LAMP2c isoforms), desmoplakin (DSP, such as DPI and DPII isoforms), desmoglein 2 (DSG2), and junction plakoglobin (JUP), or a variant of any of these polypeptides (e.g., having at least 75%, at least 85%, at least 95%, at least 97% or at least 99% sequence identity thereto). In some embodiments, the transgene in the expression cassette encodes DWORF (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes JPH2 (e.g., a full-length JPH2 or an N-terminal fragment of JPH2) (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes BAG3 (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes CRYAB (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes LMNA Lamin A isoform (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes LMNA Lamin C isoform (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes TNNI3 (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes PLN (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes LAMP2a (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes LAMP2b (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes LAMP2c (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes DSP DPI isoform (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes DSP DPII isoform (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes DSG2 (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes JUP (or a variant thereof). In some embodiments, the transgene in the expression cassette encodes a human polypeptide (such as any human polypeptide described herein). 
     In some embodiments, the expression cassettes described herein lead to cardiac cell-specific expression of a transgene. In some embodiments, the expression cassettes described herein lead to cardiomyocyte-specific expression of a transgene. In some embodiments, the expression cassettes described herein allow high expression of a transgene in a cardiac cell (e.g., a cardiomyocyte) and low or no expression in other cells (e.g., low or no expression in liver cells, low or no expression in muscle cells except for muscle cells of the heart, low or no expression in cardiac fibroblasts). In some embodiments, the expression cassettes described herein allow high expression of a transgene in heart tissue of a subject (e.g., in human heart). In some embodiments, the expression cassettes described herein allow no or low expression of a transgene in tissues of a subject other than the heart (e.g., in liver or in muscles except those of the heart). “High” and “low” can be relative to each other, for example, the expression of a transgene in cardiac cells (e.g., cardiomyocytes) and/or heart tissue can be at least 2 fold, 5 fold, 10 fold, 15 fold, 20 fold, 50 fold, 100 fold, 150 fold, or 200 fold higher than its expression in other cells and tissues (e.g., liver, muscle except for the heart). 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Illustrative Expression Cassette Sequences 
               
            
           
           
               
               
            
               
                 Expression Cassette 
                 Sequence 
               
               
                   
               
               
                 pCR-MD1 
                 
                   CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGG 
                 
               
               
                 distinct sequence elements 
                 
                   GCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAG 
                 
               
               
                 are indicated in bold, 
                 
                   CGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT 
                   TGT 
                 
               
               
                 starting with ITR, hcTnTp, 
                 
                   AGTTAATGATTAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAA 
                 
               
               
                 DWORF (which is also 
                 
                   GATCGGAATTCGCCCTTAAG 
                   GTCATGGAGAAGACCCACCTTGCAGAT 
                 
               
               
                 underlined), WPRE, poly A 
                 
                   GTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCT 
                 
               
               
                 (hGHpA), ITR 
                 
                   CAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAG 
                 
               
               
                   
                 
                   CATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGCCTTCC 
                 
               
               
                   
                 
                   AAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTT 
                 
               
               
                   
                 
                   CTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTT 
                 
               
               
                   
                 
                   GCTGGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTT 
                 
               
               
                   
                 
                   ATGTTGCATGACTGTTCCCTGCATATCTGCTCTGGTTTTAAATAGC 
                 
               
               
                   
                 
                   TTATCTGAGCAGCTGGAGGACCACATGGGCTTATATGGCGTGGGG 
                 
               
               
                   
                 
                   TACATGTTCCTGTAGCCTTGTCCCTGGCACCTGCCAAAATAGCAG 
                 
               
               
                   
                 
                   CCAACACCCCCCACCCCCACCGCCATCCCCCTGCCCCACCCGTCC 
                 
               
               
                   
                 
                   CCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCAGGCCCC 
                 
               
               
                   
                 
                   AGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCACCCA 
                 
               
               
                   
                 
                   GTCCCCGCTGAGACTGAGCAGACGCCTCCA 
                   GCGGCCGCCCGCCACC 
                 
               
               
                   
                 
                   
                     ATGGCTGAGAAAGAGTCAACATCACCACACCTCATGGTTCCCATT 
                   
                 
               
               
                   
                 
                   
                     CTTCTCCTGGTTGGATGGATTGTAGGCTGCATCATCGTTATTTACA 
                   
                 
               
               
                   
                 
                   
                     TTGTCTTCTTCTAA 
                   
                   AAGCTTTGGATCCAA 
                   TCAACCTCTGGATTACAAA 
                 
               
               
                   
                 
                   ATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTA 
                 
               
               
                   
                 
                   CGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGC 
                 
               
               
                   
                 
                   TTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTG 
                 
               
               
                   
                 
                   CTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGC 
                 
               
               
                   
                 
                   GTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGC 
                 
               
               
                   
                 
                   ATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCC 
                 
               
               
                   
                 
                   TCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCT 
                 
               
               
                   
                 
                   GCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGT 
                 
               
               
                   
                 
                   TGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTG 
                 
               
               
                   
                 
                   CCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGG 
                 
               
               
                   
                 
                   CCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTC 
                 
               
               
                   
                 
                   TGCGGCCTCTTCCGCGTCTTCG 
                   AGATCT 
                   GCCTCGACTGTGCCTTCT 
                 
               
               
                   
                 
                   AGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGA 
                 
               
               
                   
                 
                   CCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGG 
                 
               
               
                   
                 
                   AAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGG 
                 
               
               
                   
                 
                   GTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAAT 
                 
               
               
                   
                 
                   AGCAGGCATGCTGGGGA 
                   CTCGAGTTAAGGGCGAATTCCCGATTAGGAT 
                 
               
               
                   
                 
                   CTTCCTAGAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTAAC 
                 
               
               
                   
                 
                   TACA 
                   AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCG 
                 
               
               
                   
                 
                   CTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCC 
                 
               
               
                   
                 
                   CGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
                 
               
               
                   
                 (SEQ ID NO: 20) 
               
               
                   
               
               
                 pCR-MD2 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGAGAGGACCCTTTCAAGGACATTAGTGGTGGAGGC 
               
               
                   
                 AGCATAGTAGCTCCCAAGGCAGAGGGATTGAGAGAAGAGTTTGAGGA 
               
               
                   
                 CTGGGAAGGCGGGACACATGATTGGGTGATGGGAGAAGGGGGCAGAG 
               
               
                   
                 AATAGCGAGATTGCTTTCTTTGCCCACGGAGAAACAGAGGAGTGTGGA 
               
               
                   
                 TCATGAATGGGCAAGATCTTTAAGTGCCAGGGGGGGTCATGGAGGAG 
               
               
                   
                 GGGAGGGCCTGCTCCAGAGGAGGACCATTCCTGCTTCAGAGCCAAGC 
               
               
                   
                 AGGACCTAGGCTGTGAAGATTCGGAGAAAGAGATGGAGGGGAGAGTC 
               
               
                   
                 AGCTCAGCTGCTTACTGGCTTGCTTTCCTCCTGTCTCTTTCATTTTCATA 
               
               
                   
                 ATCTACCAAACCCTGCAATGGGCCAGCCTTGAACATACAAGTGCATGT 
               
               
                   
                 GCATGGTCAGACACAGGCAAGCAAGCAAGACCCCTAGGCCTGACCTA 
               
               
                   
                 TGCATCTGCAATCTAGTAGGTTTAGCAGATCATAGCCCCGCACTGCTT 
               
               
                   
                 GATTTTAAAGCCGTTAGGGGATGACCTTTGACAGTCCGCATCACCCCT 
               
               
                   
                 CTCACACAACGAGCGCCTGTTCAAGGTTCTTGACTGGAAGTTCTACCT 
               
               
                   
                 TGTATCTGGCCTCCTGTAGCAGTTTCAGTCCATTCCCTGTGAGGAGGGT 
               
               
                   
                 GTGCCACATGGCTTTGGGGGTCATGGAGAAGACCCACCTTGCAGATGT 
               
               
                   
                 CCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTC 
               
               
                   
                 CATTAGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTT 
               
               
                   
                 CAAGTGGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGG 
               
               
                   
                 TGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCC 
               
               
                   
                 TGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATC 
               
               
                   
                 AGGATTCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTG 
               
               
                   
                 CATATCTGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCA 
               
               
                   
                 CATGGGCTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGG 
               
               
                   
                 CACCTGCCAAAATAGCAGCCAACACCCCCGACCCCCACCGCCATCCCC 
               
               
                   
                 CTGCCCCACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCT 
               
               
                   
                 CACCAGGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTG 
               
               
                   
                 CCTCACCCAGTCCCCGCTGAGACTGAGCAGACGCCTCCAGGATCTGTC 
               
               
                   
                 GGCAGCTGCTGTTCTGAGGTAAGGCTCGGGCAGGGCTCTGGGGAAGA 
               
               
                   
                 GGAGAGCAGAGAATGGACGGGGAGATGTGAGGGTCTTGGGCCCTGGC 
               
               
                   
                 ATATTTACCCAGAGTCTGCCTGTGTCCGCAGAAGTCCATGGCCCCTCCT 
               
               
                   
                 GGTGGAGGCCACACTTCAGAGGACAGGTTGCCAGGTCTGGGCTCCAA 
               
               
                   
                 GATTGGTACAATAGAGCAGAGAGAGGAGTCGCTGCGACGCTGCCTTC 
               
               
                   
                 GCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCCGCCCCGGCTCT 
               
               
                   
                 GACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTC 
               
               
                   
                 CTCCGGGCTGTAATTAGCGCTTGGTTTAATGACGGCTTGTTTCTTTTCT 
               
               
                   
                 GTGGCTGCGTGAAAGCCTTGAGGGGCTCCGGGAGCTAGAGCCTCTGCT 
               
               
                   
                 AACCATGTTCATGCCTTCTTCTTTTTCCTACAGCTCCTGGGCAACGTGC 
               
               
                   
                 TGGTTATTGTGCTGTCTCATCATTTTGGCAAAGAATTCCCAATCGATAC 
               
               
                   
                 CCAATCGATACAGATCTAGCGGCCGCGCCGCCACCATGGCTGAGAAA 
               
               
                   
                 GAGTCAACATCACCACACCTCATGGTTCCCATTCTTCTCCTGGTTGGAT 
               
               
                   
                 GGATTGTAGGCTGCATCATCGTTATTTACATTGTCTTCTTCTAACCAGA 
               
               
                   
                 GGTTGATTGGATCCAAGCTTTGGATCCAATGGATCCAATCAACCTCTG 
               
               
                   
                 GATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTC 
               
               
                   
                 CTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTAT 
               
               
                   
                 TGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGC 
               
               
                   
                 TGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGG 
               
               
                   
                 TGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCA 
               
               
                   
                 CCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGC 
               
               
                   
                 CACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGC 
               
               
                   
                 TCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATC 
               
               
                   
                 GTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGG 
               
               
                   
                 ACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTT 
               
               
                   
                 CCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCT 
               
               
                   
                 GCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCC 
               
               
                   
                 CCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTA 
               
               
                   
                 ATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTAT 
               
               
                   
                 TCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAA 
               
               
                   
                 GACAATAGCAGGCATGCTGGGGACTCGAGTTAAGGGCGAATTCCCGA 
               
               
                   
                 TTAGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGCATGGCGGGT 
               
               
                   
                 TAATCATTAACTACAAGGAACCCCTAGTGATGGAGTTGGCCACTCCCT 
               
               
                   
                 CTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCC 
               
               
                   
                 GACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGC 
               
               
                   
                 AG (SEQ ID NO: 21) 
               
               
                   
               
               
                 pCR-HD1 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGGTCATGGAGAAGACCCACCTTGCAGATGTCCTCA 
               
               
                   
                 CTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATTA 
               
               
                   
                 GGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAGT 
               
               
                   
                 GGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCAGCGGCCGCCCGCCAC 
               
               
                   
                 CATGGCAGAGAAGGCTGGAAGCACTTTCTCTCACCTGCTCGTGCCGAT 
               
               
                   
                 TTTGCTTTTGATTGGGTGGATAGTTGGCTGTATCATAATGATCTACGTT 
               
               
                   
                 GTCTTTTCATAGAAGCTTTGGATCCAATCAACCTCTGGATTACAAAATT 
               
               
                   
                 TGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTAT 
               
               
                   
                 GTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTAT 
               
               
                   
                 GGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATG 
               
               
                   
                 AGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGT 
               
               
                   
                 TTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGC 
               
               
                   
                 TCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACT 
               
               
                   
                 CATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGG 
               
               
                   
                 CACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGG 
               
               
                   
                 CTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCT 
               
               
                   
                 ACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCT 
               
               
                   
                 GCCGGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCTGCCTCGACTGTGC 
               
               
                   
                 CTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTG 
               
               
                   
                 ACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAA 
               
               
                   
                 ATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGG 
               
               
                   
                 GTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGC 
               
               
                   
                 ATGCTGGGGACTCGAGTTAAGGGCGAATTCCCGATTAGGATCTTCCTA 
               
               
                   
                 GAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTAACTAC 
               
               
                   
                 AAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGC 
               
               
                   
                 TCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTT 
               
               
                   
                 GCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID NO: 22) 
               
               
                   
               
               
                 pCR-HD2 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGAGAGGACCCTTTCAAGGACATTAGTGGTGGAGGC 
               
               
                   
                 AGCATAGTAGCTCCCAAGGCAGAGGGATTGAGAGAAGAGTTTGAGGA 
               
               
                   
                 CTGGGAAGGCGGGACACATGATTGGGTGATGGGAGAAGGGGGCAGAG 
               
               
                   
                 AATAGCGAGATTGCTTTCTTTGCCCACGGAGAAACAGAGGAGTGTGGA 
               
               
                   
                 TCATGAATGGGCAAGATCTTTAAGTGCCAGGGGGGGTCATGGAGGAG 
               
               
                   
                 GGGAGGGCCTGCTCCAGAGGAGGACCATTCCTGCTTCAGAGCCAAGC 
               
               
                   
                 AGGACCTAGGCTGTGAAGATTCGGAGAAAGAGATGGAGGGGAGAGTC 
               
               
                   
                 AGCTCAGCTGCTTACTGGCTTGCTTTCCTCCTGTCTCTTTCATTTTCATA 
               
               
                   
                 ATCTACCAAACCCTGCAATGGGCCAGCCTTGAACATACAAGTGCATGT 
               
               
                   
                 GCATGGTCAGACACAGGCAAGCAAGCAAGACCCCTAGGCCTGACCTA 
               
               
                   
                 TGCATCTGCAATCTAGTAGGTTTAGCAGATCATAGCCCCGCACTGCTT 
               
               
                   
                 GATTTTAAAGCCGTTAGGGGATGACCTTTGACAGTCCGCATCACCCCT 
               
               
                   
                 CTCACACAACGAGCGCCTGTTCAAGGTTCTTGACTGGAAGTTCTACCT 
               
               
                   
                 TGTATCTGGCCTCCTGTAGCAGTTTCAGTCCATTCCCTGTGAGGAGGGT 
               
               
                   
                 GTGCCACATGGCTTTGGGGGTCATGGAGAAGACCCACCTTGCAGATGT 
               
               
                   
                 CCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTC 
               
               
                   
                 CATTAGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTT 
               
               
                   
                 CAAGTGGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGG 
               
               
                   
                 TGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCC 
               
               
                   
                 TGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATC 
               
               
                   
                 AGGATTCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTG 
               
               
                   
                 CATATCTGCTCTGGTTTAAATAGCTTATCTGAGCAGCTGGAGGACCA 
               
               
                   
                 CATGGGCTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGG 
               
               
                   
                 CACCTGCCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCC 
               
               
                   
                 CTGCCCCACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCT 
               
               
                   
                 CACCAGGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTG 
               
               
                   
                 CCTCACCCAGTCCCCGCTGAGACTGAGCAGACGCCTCCAGGATCTGTC 
               
               
                   
                 GGCAGCTGCTGTTCTGAGGTAAGGCTCGGGCAGGGCTCTGGGGAAGA 
               
               
                   
                 GGAGAGCAGAGAATGGACGGGGAGATGTGAGGGTCTTGGGCCCTGGC 
               
               
                   
                 ATATTTACCCAGAGTCTGCCTGTGTCCGCAGAAGTCCATGGCCCCTCCT 
               
               
                   
                 GGTGGAGGCCACACTTCAGAGGACAGGTTGCCAGGTCTGGGCTCCAA 
               
               
                   
                 GATTGGTACAATAGAGCAGAGAGAGGAGTCGCTGCGACGCTGCCTTC 
               
               
                   
                 GCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCCGCCCCGGCTCT 
               
               
                   
                 GACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTC 
               
               
                   
                 CTCCGGGCTGTAATTAGCGCTTGGTTTAATGACGGCTTGTTTCTTTTCT 
               
               
                   
                 GTGGCTGCGTGAAAGCCTTGAGGGGCTCCGGGAGCTAGAGCCTCTGCT 
               
               
                   
                 AACCATGTTCATGCCTTCTTCTTTTTCCTACAGCTCCTGGGCAACGTGC 
               
               
                   
                 TGGTTATTGTGCTGTCTCATCATTTTGGCAAAGAATTCCCAATCGATAC 
               
               
                   
                 CCAATCGATACAGATCTAGCGGCCGCGCCGCCACCATGGCAGAGAAG 
               
               
                   
                 GCTGGAAGCACTTTCTCTCACCTGCTCGTGCCGATTTGCTTTTGATTG 
               
               
                   
                 GGTGGATAGTTGGCTGTATCATAATGATCTACGTTGTCTTTCATAGCC 
               
               
                   
                 AGAGGTTGATTGGATCCAAGCTTTGGATCCAATGGATCCAATCAACCT 
               
               
                   
                 CTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTG 
               
               
                   
                 CTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGC 
               
               
                   
                 TATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGT 
               
               
                   
                 TGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCG 
               
               
                   
                 TGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTG 
               
               
                   
                 CCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTAT 
               
               
                   
                 TGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGG 
               
               
                   
                 GGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATC 
               
               
                   
                 ATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGC 
               
               
                   
                 GGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTC 
               
               
                   
                 CTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGAGA 
               
               
                   
                 TCTGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCT 
               
               
                   
                 CCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTC 
               
               
                   
                 CTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTC 
               
               
                   
                 TATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGG 
               
               
                   
                 AAGACAATAGCAGGCATGCTGGGGACTCGAGTTAAGGGCGAATTCCC 
               
               
                   
                 GATTAGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGCATGGCGG 
               
               
                   
                 GTTAATCATTAACTACAAGGAACCCCTAGTGATGGAGTTGGCCACTCC 
               
               
                   
                 CTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGC 
               
               
                   
                 CCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGC 
               
               
                   
                 GCAG (SEQ ID NO: 23) 
               
               
                   
               
               
                   
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACCAGGGTAATGGGGATCCTCTAGAA 
               
               
                   
                 CTATAGCTAGAATTCGCCCTTACGGGCCCCCCCTCGAGGTGGGGATAA 
               
               
                   
                 AAGCAGTCTGGGCTTTCACATGACAGCATCTGGGGCTGCGGCAGAGG 
               
               
                   
                 GTCGGGTCCGAAGCGCTGCCTTATCAGCGTCCCCAGCCCTGGGAGGTG 
               
               
                   
                 ACAGCTGGCTGGCTTGTGTCAGCCCCTCGGGCACTCACGTATCTCCGT 
               
               
                   
                 CCGACGGGTTTAAAATAGCAAAACTCTGAGGCCACACAATAGCTTGG 
               
               
                   
                 GCTTATATGGGCTCCTGTGGGGGAAGGGGGAGCACGGAGGGGGCCGG 
               
               
                   
                 GGCCGCTGCTGCCAAAATAGCAGCTCACAAGTGTTGCATTCCTCTCTG 
               
               
                   
                 GGCGCCGGGCACATTCCTGCTGGCTCTGCCCGCCCCGGGGTGGGCGCC 
               
               
                   
                 GGGGGGACCTTAAAGCCTCTGCCCCCCAAGGAGCCCTTCCCAGACAGC 
               
               
                   
                 CGCCGGCACCCACCGCTCCGTGGGACGATCCCCGAAGCTCTAGAGCTT 
               
               
                   
                 TATTGCGGTAGTTTATCACAGTTAAATTGCTAACGCAGTCAGTGCTTCT 
               
               
                   
                 GACACAACAGTCTCGAACTTAAGCTGCAGAAGTTGGTCGTGAGGCACT 
               
               
                   
                 GGGCAGGTAAGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATA 
               
               
                   
                 GAAACTGGGCTTGTCGAGACAGAGAAGACTCTTGCGTTTCTGATAGGC 
               
               
                   
                 ACCTATTGGTCTTACTGACATCCACTTTGCCTTTCTCTCCACAGGTGTC 
               
               
                   
                 CACTCCCAGTTCAATTACAGCTCTTAAGGCTAGAGTACTTAATACGAC 
               
               
                   
                 TCACTATAGGCTAGCCGCCACCATGGCTGAGAAAGAGTCAACATCACC 
               
               
                   
                 ACACCTCATGGTTCCCATTCTTCTCCTGGTTGGATGGATTGTAGGCTGC 
               
               
                   
                 ATCATCGTTATTTACATTGTCTTCTTCTAACGGCCGCGCGGATCCAGAC 
               
               
                   
                 ATGATAAGATACATTGATGAGTTTGGACAAACCACAACTAGAATGCA 
               
               
                   
                 GTGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCTATTGCTTTATTT 
               
               
                   
                 GTAACCATTATAAGCTGCAATAAACAAGTTAACAACAACAATTGCATT 
               
               
                   
                 CATTTTATGTTTCAGGTTCAGGGGGAGGTGTGGGAGGTTTTTTAGTCG 
               
               
                   
                 ACCCGGGCGGCCTCGAGGACGGGGTGAACTACGCCTGAGGATCCGAT 
               
               
                   
                 CTTTTTCCCTCTGCCAAAAATTATGGGGACATCATGAAGCCCCTTGAG 
               
               
                   
                 CATCTGACTTCTGGCTAATAAAGGAAATTTATTTTCATTGCAATAGTGT 
               
               
                   
                 GTTGGAATTTTTTGTGTCTCTCACTCGGAAGCAATTCGTTGATCTGAAT 
               
               
                   
                 TTCGACCACCCATAATACCCATTACCCTGGTAGATAAGTAGCATGGCG 
               
               
                   
                 GGTTAATCATTAACTACAAGGAACCCCTAGTGATGGAGTTGGCCACTC 
               
               
                   
                 CCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCG 
               
               
                   
                 CCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCG 
               
               
                   
                 CGCAG (SEQ ID NO: 24) 
               
               
                   
               
               
                 pHZ15 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGAACTGGCCTGCCCGAGACCAAACGTGCGGAACGT 
               
               
                   
                 AGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATTCTGATTC 
               
               
                   
                 TCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACTGTCAAA 
               
               
                   
                 TGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCTCTCCCC 
               
               
                   
                 AGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCATCCCA 
               
               
                   
                 AACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCC 
               
               
                   
                 CTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTC 
               
               
                   
                 TAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACT 
               
               
                   
                 GAAGGAAAAGCACAGCATTAGAAGTCCAAGCAGTCATGGAGAAGACC 
               
               
                   
                 CACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCT 
               
               
                   
                 AAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTAC 
               
               
                   
                 CCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGCC 
               
               
                   
                 TTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTT 
               
               
                   
                 CTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCT 
               
               
                   
                 GGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTG 
               
               
                   
                 CATGACTGTTCCCTGCATATCTGCTCTGGTTTAAATAGCTTATCTGAG 
               
               
                   
                 CAGCTGGAGGACCACATGGGCTTATATGGCGTGGGGTACATGTTCCTG 
               
               
                   
                 TAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCACC 
               
               
                   
                 CCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCC 
               
               
                   
                 TCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGC 
               
               
                   
                 CCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACG 
               
               
                   
                 CCTCCAGCGGCCGCCCGCCACCATGGCTGAGAAAGAGTCAACATCACC 
               
               
                   
                 ACACCTCATGGTTCCCATTCTTCTCCTGGTTGGATGGATTGTAGGCTGC 
               
               
                   
                 ATCATCGTTATTTACATTGTCTTCTTCTAAAAGCTTTGGATCCAATCAA 
               
               
                   
                 CCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATG 
               
               
                   
                 TTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCA 
               
               
                   
                 TGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCT 
               
               
                   
                 GGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTG 
               
               
                   
                 GCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCA 
               
               
                   
                 TTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCC 
               
               
                   
                 TATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGAC 
               
               
                   
                 AGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAA 
               
               
                   
                 ATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCTGGATTCTG 
               
               
                   
                 CGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGAC 
               
               
                   
                 CTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTC 
               
               
                   
                 GAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGC 
               
               
                   
                 CCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCC 
               
               
                   
                 TTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTC 
               
               
                   
                 ATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGAT 
               
               
                   
                 TGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGTTAAGGGCGAAT 
               
               
                   
                 TCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGCATG 
               
               
                   
                 GCGGGTTAATCATTAACTACAAGGAACCCCTAGTGATGGAGTTGGCCA 
               
               
                   
                 CTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGG 
               
               
                   
                 TCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAG 
               
               
                   
                 CGCGCAG (SEQ ID NO: 45) 
               
               
                   
               
               
                 pHZ16 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGAACTGGCCTGCCCGAGACCAAACGTGCGGAACGT 
               
               
                   
                 AGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATTCTGATTC 
               
               
                   
                 TCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACTGTCAAA 
               
               
                   
                 TGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCTCTCCCC 
               
               
                   
                 AGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCATCCCA 
               
               
                   
                 AACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCC 
               
               
                   
                 CTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTC 
               
               
                   
                 TAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACT 
               
               
                   
                 GAAGGAAAAGCACAGCATTAGAAGTCCAAGCACCTTCAGATTAAAAA 
               
               
                   
                 TAACTAAGGTAAGGGCCATGTGGGTAGGGGAGGTGGTGTGAGACGGT 
               
               
                   
                 CCTGTCTCTCCTCTATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTG 
               
               
                   
                 CCCAAGGACTAAAAAAAGGCCCTGGAGCCAGAGGGGCGAGGGCAGC 
               
               
                   
                 AGACCTTTCATGGGCAAACCTCAGGGCTGCTGTCGTCATGGAGAAGAC 
               
               
                   
                 CCACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCC 
               
               
                   
                 TAAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTA 
               
               
                   
                 CCCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGC 
               
               
                   
                 CTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCT 
               
               
                   
                 TCTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCT 
               
               
                   
                 GGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTG 
               
               
                   
                 CATGACTGTTCCCTGCATATCTGCTCTGGTTTTAAATAGCTTATCTGAG 
               
               
                   
                 CAGCTGGAGGACCACATGGGCTTATATGGCGTGGGGTACATGTTCCTG 
               
               
                   
                 TAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCACC 
               
               
                   
                 CCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCC 
               
               
                   
                 TCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGC 
               
               
                   
                 CCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACG 
               
               
                   
                 CCTCCAGCGGCCGCCCGCCACCATGGCTGAGAAAGAGTCAACATCACC 
               
               
                   
                 ACACCTCATGGTTCCCATTCTTCTCCTGGTTGGATGGATTGTAGGCTGC 
               
               
                   
                 ATCATCGTTATTTACATTGTCTTCTTCTAAAAGCTTTGGATCCAATCAA 
               
               
                   
                 CCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATG 
               
               
                   
                 TTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCA 
               
               
                   
                 TGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCT 
               
               
                   
                 GGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTG 
               
               
                   
                 GCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCA 
               
               
                   
                 TTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCC 
               
               
                   
                 TATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGAC 
               
               
                   
                 AGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAA 
               
               
                   
                 ATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCTGGATTCTG 
               
               
                   
                 CGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGAC 
               
               
                   
                 CTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTC 
               
               
                   
                 GAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGC 
               
               
                   
                 CCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCC 
               
               
                   
                 TTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTC 
               
               
                   
                 ATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGAT 
               
               
                   
                 TGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGTTAAGGGCGAAT 
               
               
                   
                 TCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGCATG 
               
               
                   
                 GCGGGTTAATCATTAACTACAAGGAACCCCTAGTGATGGAGTTGGCCA 
               
               
                   
                 CTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGG 
               
               
                   
                 TCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAG 
               
               
                   
                 CGCGCAG (SEQ ID NO: 46) 
               
               
                   
               
               
                 pHZ17 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGCCTTCAGATTAAAAATAACTAAGGTAAGGGCCAT 
               
               
                   
                 GTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCCTCTATCTGC 
               
               
                   
                 CCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAAAAAAAG 
               
               
                   
                 GCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTTCATGGGCAAAC 
               
               
                   
                 CTCAGGGCTGCTGTCGTCATGGAGAAGACCCACCTTGCAGATGTCCTC 
               
               
                   
                 ACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATT 
               
               
                   
                 AGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAG 
               
               
                   
                 TGGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCAGCGGCCGCCCGCCAC 
               
               
                   
                 CATGGCTGAGAAAGAGTCAACATCACCACACCTCATGGTTCCCATTCT 
               
               
                   
                 TCTCCTGGTTGGATGGATTGTAGGCTGCATCATCGTTATTTACATTGTC 
               
               
                   
                 TTCTTCTAAAAGCTTTGGATCCAATCAACCTCTGGATTACAAAATTTGT 
               
               
                   
                 GAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTATGTG 
               
               
                   
                 GATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTATGGC 
               
               
                   
                 TTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGG 
               
               
                   
                 AGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTG 
               
               
                   
                 CTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGCTCC 
               
               
                   
                 TTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCAT 
               
               
                   
                 CGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCAC 
               
               
                   
                 TGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTG 
               
               
                   
                 CTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACG 
               
               
                   
                 TCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCC 
               
               
                   
                 GGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCTGCCTCGACTGTGCCTT 
               
               
                   
                 CTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGAC 
               
               
                   
                 CCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAAT 
               
               
                   
                 TGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGT 
               
               
                   
                 GGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCAT 
               
               
                   
                 GCTGGGGACTCGAGTTAAGGGCGAATTCCCGATTAGGATCTTCCTAGA 
               
               
                   
                 GCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTAACTACAA 
               
               
                   
                 GGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTC 
               
               
                   
                 GCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGC 
               
               
                   
                 CCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID NO: 47) 
               
               
                   
               
               
                 pHZ18 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGCCTTCAGATTAAAAATAACTAAGGTAAGGGCCAT 
               
               
                   
                 GTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCCTCTATCTGC 
               
               
                   
                 CCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAAAAAAAG 
               
               
                   
                 GCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTTCATGGGCAAAC 
               
               
                   
                 CTCAGGGCTGCTGTCAACTGGCCTGCCCGAGACCAAACGTGCGGAACG 
               
               
                   
                 TAGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATTCTGATT 
               
               
                   
                 CTCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACTGTCAA 
               
               
                   
                 ATGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCTCTCCC 
               
               
                   
                 CAGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCATCCCA 
               
               
                   
                 AACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCC 
               
               
                   
                 CTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTC 
               
               
                   
                 TAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACT 
               
               
                   
                 GAAGGAAAAGCACAGCATTAGAAGTCCAAGCAGTCATGGAGAAGACC 
               
               
                   
                 CACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCT 
               
               
                   
                 AAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTAC 
               
               
                   
                 CCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGCC 
               
               
                   
                 TTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTT 
               
               
                   
                 CTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCT 
               
               
                   
                 GGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTG 
               
               
                   
                 CATGACTGTTCCCTGCATATCTGCTCTGGTTTAAATAGCTTATCTGAG 
               
               
                   
                 CAGCTGGAGGACCACATGGGCTTATATGGCGTGGGGTACATGTTCCTG 
               
               
                   
                 TAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCACC 
               
               
                   
                 CCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCC 
               
               
                   
                 TCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGC 
               
               
                   
                 CCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACG 
               
               
                   
                 CCTCCAGCGGCCGCCCGCCACCATGGCTGAGAAAGAGTCAACATCACC 
               
               
                   
                 ACACCTCATGGTTCCCATTCTTCTCCTGGTTGGATGGATTGTAGGCTGC 
               
               
                   
                 ATCATCGTTATTTACATTGTCTTCTTCTAAAAGCTTTGGATCCAATCAA 
               
               
                   
                 CCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATG 
               
               
                   
                 TTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCA 
               
               
                   
                 TGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCT 
               
               
                   
                 GGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTG 
               
               
                   
                 GCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCA 
               
               
                   
                 TTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCC 
               
               
                   
                 TATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGAC 
               
               
                   
                 AGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAA 
               
               
                   
                 ATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCTGGATTCTG 
               
               
                   
                 CGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCGGAC 
               
               
                   
                 CTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTC 
               
               
                   
                 GAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGC 
               
               
                   
                 CCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCC 
               
               
                   
                 TTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTC 
               
               
                   
                 ATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGAT 
               
               
                   
                 TGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGTTAAGGGCGAAT 
               
               
                   
                 TCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGCATG 
               
               
                   
                 GCGGGTTAATCATTAACTACAAGGAACCCCTAGTGATGGAGTTGGCCA 
               
               
                   
                 CTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGG 
               
               
                   
                 TCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAG 
               
               
                   
                 CGCGCAG (SEQ ID NO: 48) 
               
               
                   
               
               
                 pHZ19 
                 
                   CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGG 
                 
               
               
                 distinct sequence elements 
                 
                   GCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAG 
                 
               
               
                 are indicated in bold, 
                 
                   CGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT 
                   TGT 
                 
               
               
                 starting with ITR, 
                 
                   AGTTAATGATTAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAA 
                 
               
               
                 enhancer/promoter combo 
                 
                   GATCGGAATTCGCCCTTAAG 
                   CCTTCAGATTAAAAATAACTAAGGTAAG 
                 
               
               
                 (αMHCe, followed by 
                 
                   GGCCATGTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCC 
                 
               
               
                 ACTC1e, followed by 
                 
                   TCTATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGG 
                 
               
               
                 hcTnTp), DWORF (which 
                 
                   ACTAAAAAAAGGCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACC 
                 
               
               
                 is also underlined), WPRE, 
                 
                   TTTCATGGGCAAACCTCAGGGCTGCTGTCAACTGGCCTGCCCGAG 
                 
               
               
                 polyA (hGHpA), ITR 
                 
                   ACCAAACGTGCGGAACGTAGTTAAGTGTTAGAGGTAGGATTTGAA 
                 
               
               
                   
                 
                   GCCTGTCGATCATTCTGATTCTCCTTTTCTCTACGTCTGCTTCCTG 
                 
               
               
                   
                 
                   TCAATGGGCATCCTCACTGTCAAATGCAGATGGTACAGCAGGGCT 
                 
               
               
                   
                 
                   TGGTCTCAGCCAGGCAGGCCTCTCCCCAGTCTCCATGGCTCAGCT 
                 
               
               
                   
                 
                   GTCCAGCAGTTTCATCCCTAGACCATCCCAAACATGGTTGAGAAG 
                 
               
               
                   
                 
                   CTCTGAGGGGAGGACCCAGCACTGCCCGGCCCCTGAAGATAATCA 
                 
               
               
                   
                 
                   GCAGTCCTGCTCAGCATATCAATCCAAGCCCACTCTAGACAGAGA 
                 
               
               
                   
                 
                   TGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACTGAAGGAA 
                 
               
               
                   
                 
                   AAGCACAGCATTAGAAGTCCAAGCAGTCATGGAGAAGACCCACCT 
                 
               
               
                   
                 
                   TGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCTAA 
                 
               
               
                   
                 
                   GGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTA 
                 
               
               
                   
                 
                   CCCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTC 
                 
               
               
                   
                 
                   TGCCTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAG 
                 
               
               
                   
                 
                   GTTGCCTTCTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGG 
                 
               
               
                   
                 
                   CCTGGGTTGCTGGCCTCTGCTTTATCAGGATTCTCAAGAGGGACA 
                 
               
               
                   
                 
                   GCTGGTTTATGTTGCATGACTGTTCCCTGCATATCTGCTCTGGTTT 
                 
               
               
                   
                 
                   TAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGGCTTATATG 
                 
               
               
                   
                 
                   GCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTGCCAA 
                 
               
               
                   
                 
                   AATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCCC 
                 
               
               
                   
                 
                   ACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCAC 
                 
               
               
                   
                 
                   CAGGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTG 
                 
               
               
                   
                 
                   CCTCACCCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAACTG 
                 
               
               
                   
                 
                   GTAAGTACCGCCTATAGACTCTATAGGCACACCCCTTTGGCTCTTA 
                 
               
               
                   
                 
                   TGCATGCTGACAGACTAACAGACTGTTCCTTTCCTGGGTCTTTTCT 
                 
               
               
                   
                 
                   GCAGGCCTGTACGGAAGTGTTACTTCTGCTCTAAAAGCTGCGGAA 
                 
               
               
                   
                 
                   TTGTACCCGCGGCCGATCCAATCGATACAGATCTAGCGGCC 
                   GCCC 
                 
               
               
                   
                 
                   GCCACC 
                   
                     ATGGCTGAGAAAGAGTCAACATCACCACACCTCATGGTTC 
                   
                 
               
               
                   
                 
                   
                     CCATTCTTCTCCTGGTTGGATGGATTGTAGGCTGCATCATCGTTAT 
                   
                 
               
               
                   
                 
                   
                     TTACATTGTCTTCTTCTAA 
                   
                   AAGCTTTGGATCCAA 
                   TCAACCTCTGGATT 
                 
               
               
                   
                 
                   ACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCC 
                 
               
               
                   
                 
                   TTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCT 
                 
               
               
                   
                 
                   ATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCT 
                 
               
               
                   
                 
                   GGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAAC 
                 
               
               
                   
                 
                   GTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTT 
                 
               
               
                   
                 
                   GGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTT 
                 
               
               
                   
                 
                   TCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTG 
                 
               
               
                   
                 
                   CCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCG 
                 
               
               
                   
                 
                   TGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCT 
                 
               
               
                   
                 
                   GTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCC 
                 
               
               
                   
                 
                   CTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGC 
                 
               
               
                   
                 
                   CGGCTCTGCGGCCTCTTCCGCGTCTTCG 
                   AGATCT 
                   GCCTCGACTGTG 
                 
               
               
                   
                 
                   CCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTT 
                 
               
               
                   
                 
                   CCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAA 
                 
               
               
                   
                 
                   TGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTG 
                 
               
               
                   
                 
                   GGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAG 
                 
               
               
                   
                 
                   ACAATAGCAGGCATGCTGGGGA 
                   
                   
                 
               
               
                   
                 
                   
                   
                   
                 
               
               
                   
                 
                   
                   AGGAACCCCTAGTGATGGAGTTGGCCACTCCCT 
                 
               
               
                   
                 
                   CTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCG 
                 
               
               
                   
                 
                   CCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGA 
                 
               
               
                   
                   GCGCGCAG  (SEQ ID NO: 49) 
               
               
                   
               
               
                 pHZ20 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGGTCATGGAGAAGACCCACCTTGCAGATGTCCTCA 
               
               
                   
                 CTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATTA 
               
               
                   
                 GGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAGT 
               
               
                   
                 GGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAACTGGTAAGTACC 
               
               
                   
                 GCCTATAGACTCTATAGGCACACCCCTTTGGCTCTTATGCATGCTGACA 
               
               
                   
                 GACTAACAGACTGTTCCTTTCCTGGGTCTTTTCTGCAGGCCTGTACGGA 
               
               
                   
                 AGTGTTACTTCTGCTCTAAAAGCTGCGGAATTGTACCCGCGGCCGATC 
               
               
                   
                 CAATCGATACAGATCTAGCGGCCGCCCGCCACCATGGCTGAGAAAGA 
               
               
                   
                 GTCAACATCACCACACCTCATGGTTCCCATTCTTCTCCTGGTTGGATGG 
               
               
                   
                 ATTGTAGGCTGCATCATCGTTATTTACATTGTCTTCTTCTAAAAGCTTT 
               
               
                   
                 GGATCCAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGT 
               
               
                   
                 ATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAA 
               
               
                   
                 TGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCC 
               
               
                   
                 TTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTG 
               
               
                   
                 TCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCA 
               
               
                   
                 CTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGC 
               
               
                   
                 TTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCC 
               
               
                   
                 CGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTG 
               
               
                   
                 TTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCA 
               
               
                   
                 CCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAA 
               
               
                   
                 TCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTT 
               
               
                   
                 CCGCGTCTTCGAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCCATC 
               
               
                   
                 TGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACT 
               
               
                   
                 CCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTG 
               
               
                   
                 AGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAA 
               
               
                   
                 GGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGTT 
               
               
                   
                 AAGGGCGAATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGAT 
               
               
                   
                 AAGTAGCATGGCGGGTTAATCATTAACTACAAGGAACCCCTAGTGATG 
               
               
                   
                 GAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGG 
               
               
                   
                 CGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTG 
               
               
                   
                 AGCGAGCGAGCGCGCAG (SEQ ID NO: 50) 
               
               
                   
               
               
                 pHZ21 
                 
                   CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGG 
                 
               
               
                 distinct sequence elements 
                 
                   GCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAG 
                 
               
               
                 are indicated in bold, 
                 
                   CGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT 
                   TGT 
                 
               
               
                 starting with ITR, 
                 
                   AGTTAATGATTAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAA 
                 
               
               
                 enhancer/promoter combo 
                 
                   GATCGGAATTCGCCCTTAAG 
                   AACTGGCCTGCCCGAGACCAAACGTGC 
                 
               
               
                 (ACTC1e, followed by 
                 
                   GGAACGTAGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATC 
                 
               
               
                 αMHCe, followed by 
                 
                   ATTCTGATTCTCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCAT 
                 
               
               
                 hcTnTp), DWORF (which 
                 
                   CCTCACTGTCAAATGCAGATGGTACAGCAGGGCTTGGTCTCAGCC 
                 
               
               
                 is also underlined), WPRE, 
                 
                   AGGCAGGCCTCTCCCCAGTCTCCATGGCTCAGCTGTCCAGCAGTT 
                 
               
               
                 poly A (hGHpA), ITR 
                 
                   TCATCCCTAGACCATCCCAAACATGGTTGAGAAGCTCTGAGGGGA 
                 
               
               
                   
                 
                   GGACCCAGCACTGCCCGGCCCCTGAAGATAATCAGCAGTCCTGCT 
                 
               
               
                   
                 
                   CAGCATATCAATCCAAGCCCACTCTAGACAGAGATGCCGGTGCCC 
                 
               
               
                   
                 
                   AGTTTTCTATTTTTAACTGGTGTGAACTGAAGGAAAAGCACAGCAT 
                 
               
               
                   
                 
                   TAGAAGTCCAAGCACCTTCAGATTAAAAATAACTAAGGTAAGGGC 
                 
               
               
                   
                 
                   CATGTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCCTCT 
                 
               
               
                   
                 
                   ATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACT 
                 
               
               
                   
                 
                   AAAAAAAGGCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTT 
                 
               
               
                   
                 
                   CATGGGCAAACCTCAGGGCTGCTGTCGTCATGGAGAAGACCCACC 
                 
               
               
                   
                 
                   TTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCTA 
                 
               
               
                   
                 
                   AGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTT 
                 
               
               
                   
                 
                   ACCCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCT 
                 
               
               
                   
                 
                   CTGCCTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGA 
                 
               
               
                   
                 
                   GGTTGCCTTCTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAG 
                 
               
               
                   
                 
                   GCCTGGGTTGCTGGCCTCTGCTTTATCAGGATTCTCAAGAGGGAC 
                 
               
               
                   
                 
                   AGCTGGTTTATGTTGCATGACTGTTCCCTGCATATCTGCTCTGGTT 
                 
               
               
                   
                 
                   TTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGGCTTATAT 
                 
               
               
                   
                 
                   GGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTGCCA 
                 
               
               
                   
                 
                   AAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
                 
               
               
                   
                 
                   CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCA 
                 
               
               
                   
                 
                   CCAGGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCT 
                 
               
               
                   
                 
                   GCCTCACCCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAACT 
                 
               
               
                   
                 
                   GGTAAGTACCGCCTATAGACTCTATAGGCACACCCCTTTGGCTCTT 
                 
               
               
                   
                 
                   ATGCATGCTGACAGACTAACAGACTGTTCCTTTCCTGGGTCTTTTC 
                 
               
               
                   
                 
                   TGCAGGCCTGTACGGAAGTGTTACTTCTGCTCTAAAAGCTGCGGA 
                 
               
               
                   
                 
                   ATTGTACCCGCGGCCGATCCAATCGATACAGATCTA 
                   GCGGCCGCCC 
                 
               
               
                   
                 
                   GCCACC 
                   
                     ATGGCTGAGAAAGAGTCAACATCACCACACCTCATGGTTC 
                   
                 
               
               
                   
                 
                   
                     CCATTCTTCTCCTGGTTGGATGGATTGTAGGCTGCATCATCGTTAT 
                   
                 
               
               
                   
                 
                   
                     TTACATTGTCTTCTTCTAA 
                   
                   AAGCTTTGGATCCAA 
                   TCAACCTCTGGATT 
                 
               
               
                   
                 
                   ACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCC 
                 
               
               
                   
                 
                   TTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCT 
                 
               
               
                   
                 
                   ATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCT 
                 
               
               
                   
                 
                   GGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAAC 
                 
               
               
                   
                 
                   GTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTT 
                 
               
               
                   
                 
                   GGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTT 
                 
               
               
                   
                 
                   TCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTG 
                 
               
               
                   
                 
                   CCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCG 
                 
               
               
                   
                 
                   TGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCT 
                 
               
               
                   
                 
                   GTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCC 
                 
               
               
                   
                 
                   CTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGC 
                 
               
               
                   
                 
                   CGGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCTGCCTCGACTGTG 
                 
               
               
                   
                 
                   CCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTT 
                 
               
               
                   
                 
                   CCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAA 
                 
               
               
                   
                 
                   TGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTG 
                 
               
               
                   
                 
                   GGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAG 
                 
               
               
                   
                 
                   ACAATAGCAGGCATGCTGGGGA 
                   CTCGAGTTAAGGGCGAATTCCCGATT 
                 
               
               
                   
                 
                   AGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATC 
                 
               
               
                   
                 
                   ATTAACTACA 
                   AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCT 
                 
               
               
                   
                 
                   GCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCC 
                 
               
               
                   
                 
                   GACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCG 
                 
               
               
                   
                   CGCAG  (SEQ ID NO: 51) 
               
               
                   
               
               
                 pHZ22 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGAACTGGCCTGCCCGAGACCAAACGTGCGGAACGT 
               
               
                   
                 AGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATTCTGATTC 
               
               
                   
                 TCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACTGTCAAA 
               
               
                   
                 TGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCTCTCCCC 
               
               
                   
                 AGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCATCCCA 
               
               
                   
                 AACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCC 
               
               
                   
                 CTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTC 
               
               
                   
                 TAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACT 
               
               
                   
                 GAAGGAAAAGCACAGCATTAGAAGTCCAAGCAGTCATGGAGAAGACC 
               
               
                   
                 CACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCT 
               
               
                   
                 AAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTAC 
               
               
                   
                 CCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGCC 
               
               
                   
                 TTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTT 
               
               
                   
                 CTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCT 
               
               
                   
                 GGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTG 
               
               
                   
                 CATGACTGTTCCCTGCATATCTGCTCTGGTTTTAAATAGCTTATCTGAG 
               
               
                   
                 CAGCTGGAGGACCACATGGGCTTATATGGCGTGGGGTACATGTTCCTG 
               
               
                   
                 TAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCACC 
               
               
                   
                 CCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCC 
               
               
                   
                 TCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGC 
               
               
                   
                 CCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACG 
               
               
                   
                 CCTCCATAACTGGTAAGTACCGCCTATAGACTCTATAGGCACACCCCT 
               
               
                   
                 TTGGCTCTTATGCATGCTGACAGACTAACAGACTGTTCCTTTCCTGGGT 
               
               
                   
                 CTTTTCTGCAGGCCTGTACGGAAGTGTTACTTCTGCTCTAAAAGCTGCG 
               
               
                   
                 GAATTGTACCCGCGGCCGATCCAATCGATACAGATCTAGCGGCCGCCC 
               
               
                   
                 GCCACCATGGCTGAGAAAGAGTCAACATCACCACACCTCATGGTTCCC 
               
               
                   
                 ATTCTTCTCCTGGTTGGATGGATTGTAGGCTGCATCATCGTTATTTACA 
               
               
                   
                 TTGTCTTCTTCTAAAAGCTTTGGATCCAATCAACCTCTGGATTACAAAA 
               
               
                   
                 TTFGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCT 
               
               
                   
                 ATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGT 
               
               
                   
                 ATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTA 
               
               
                   
                 TGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGT 
               
               
                   
                 GTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCA 
               
               
                   
                 GCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAA 
               
               
                   
                 CTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTG 
               
               
                   
                 GGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTT 
               
               
                   
                 GGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTG 
               
               
                   
                 CTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTG 
               
               
                   
                 CTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCTGCCTCGACTGT 
               
               
                   
                 GCGTTCTAGTTGCCAGCGATCTGTTGTTTGCCCCTCCCCCGTGCCTTCC 
               
               
                   
                 TTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAG 
               
               
                   
                 GAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGT 
               
               
                   
                 GGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCA 
               
               
                   
                 GGCATGCTGGGGACTCGAGTTAAGGGCGAATTCCCGATTAGGATCTTC 
               
               
                   
                 CTAGAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTAAC 
               
               
                   
                 TACAAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCT 
               
               
                   
                 CGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGG 
               
               
                   
                 CTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID NO: 
               
               
                   
                 52) 
               
               
                   
               
               
                 pHZ23 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGCCTTCAGATTAAAAATAACTAAGGTAAGGGCCAT 
               
               
                   
                 GTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCCTCTATCTGC 
               
               
                   
                 CCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAAAAAAAG 
               
               
                   
                 GCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTTCATGGGCAAAC 
               
               
                   
                 CTCAGGGCTGCTGTCGTCATGGAGAAGACCCACCTTGCAGATGTCCTC 
               
               
                   
                 ACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATT 
               
               
                   
                 AGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAG 
               
               
                   
                 TGGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAACTGGTAAGTACC 
               
               
                   
                 GCCTATAGACTCTATAGGCACACCCCTTTGGCTCTTATGCATGCTGACA 
               
               
                   
                 GACTAACAGACTGTTCCTTTCCTGGGTCTTTTCTGCAGGCCTGTACGGA 
               
               
                   
                 AGTGTTACTTCTGCTCTAAAAGCTGCGGAATTGTACCCGCGGCCGATC 
               
               
                   
                 CAATCGATACAGATCTAGCGGCCGCCCGCCACCATGGCTGAGAAAGA 
               
               
                   
                 GTCAACATCACCACACCTCATGGTTCCCATTCTTCTCCTGGTTGGATGG 
               
               
                   
                 ATTGTAGGCTGCATCATCGTTATTTACATTGTCTTCTTCTAAAAGCTTT 
               
               
                   
                 GGATCCAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGT 
               
               
                   
                 ATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAA 
               
               
                   
                 TGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCC 
               
               
                   
                 TTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTG 
               
               
                   
                 TCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCA 
               
               
                   
                 CTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGC 
               
               
                   
                 TTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCC 
               
               
                   
                 CGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTG 
               
               
                   
                 TTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCA 
               
               
                   
                 CCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAA 
               
               
                   
                 TCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTT 
               
               
                   
                 CCGCGTCTTCGAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCCATC 
               
               
                   
                 TGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACT 
               
               
                   
                 CCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTG 
               
               
                   
                 AGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAA 
               
               
                   
                 GGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGTT 
               
               
                   
                 AAGGGCGAATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGAT 
               
               
                   
                 AAGTAGCATGGCGGGTTAATCATTAACTACAAGGAACCCCTAGTGATG 
               
               
                   
                 GAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGG 
               
               
                   
                 CGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTG 
               
               
                   
                 AGCGAGCGAGCGCGCAG (SEQ ID NO: 53) 
               
               
                   
               
               
                 pHZ24 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                   
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGGTCATGGAGAAGACCCACCTTGCAGATGTCCTCA 
               
               
                   
                 CTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATTA 
               
               
                   
                 GGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAGT 
               
               
                   
                 GGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCAGCGGCCGCCCGCCAC 
               
               
                   
                 CATGGCCGAGAAGGAATCTACCAGCCCCCACCTGATGGTGCCTATTCT 
               
               
                   
                 GCTGCTGGTGGGCTGGATCGTCGGCTGCATCATCGTGATCTACATCGT 
               
               
                   
                 GTTCTTCTGAAAGCTTTGGATCCAATCAACCTCTGGATTACAAAATTTG 
               
               
                   
                 TGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTATGT 
               
               
                   
                 GGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTATGG 
               
               
                   
                 CTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAG 
               
               
                   
                 GAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTT 
               
               
                   
                 GCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGCTC 
               
               
                   
                 CTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCA 
               
               
                   
                 TCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCA 
               
               
                   
                 CTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCT 
               
               
                   
                 GCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTAC 
               
               
                   
                 GTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGC 
               
               
                   
                 CGGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCTGCCTCGACTGTGCCT 
               
               
                   
                 TCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGA 
               
               
                   
                 CCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAA 
               
               
                   
                 TTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGT 
               
               
                   
                 GGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCAT 
               
               
                   
                 GCTGGGGACTCGAGTTAAGGGCGAATTCCCGATTAGGATCTTCCTAGA 
               
               
                   
                 GCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTAACTACAA 
               
               
                   
                 GGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTC 
               
               
                   
                 GCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGC 
               
               
                   
                 CCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID NO: 54) 
               
               
                   
               
               
                 pHZ25 
                 
                   CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGG 
                 
               
               
                 distinct sequence elements 
                 
                   GCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAG 
                 
               
               
                 are indicated in bold, 
                 
                   CGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT 
                   TGT 
                 
               
               
                 starting with ITR, 
                 
                   AGTTAATGATTAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAA 
                 
               
               
                 promoter/enhancer combo 
                 
                   GATCGGAATTCGCCCTTAAG 
                   CCTTCAGATTAAAAATAACTAAGGTAAG 
                 
               
               
                 (αMHCe, followed by 
                 
                   GGCCATGTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCC 
                 
               
               
                 hcTnTp), DWORF (which 
                 
                   TCTATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGG 
                 
               
               
                 is also underlined), WPRE, 
                 
                   ACTAAAAAAAGGCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACC 
                 
               
               
                 poly A (hGHpA) SV40pA, 
                 
                   TTTCATGGGCAAACCTCAGGGCTGCTGTCGTCATGGAGAAGACCC 
                 
               
               
                 optimized DWORF (which 
                 
                   ACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGC 
                 
               
               
                 is also underlined), 
                 
                   CTAAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTC 
                 
               
               
                 promoter/enhancer combo 
                 
                   TTTACCCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGC 
                 
               
               
                 (ccTnTp, followed by 
                 
                   CCTCTGCCTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTG 
                 
               
               
                 ACTC1e), ITR 
                 
                   GAGGTTGCCTTCTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCC 
                 
               
               
                   
                 
                   AGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGATTCTCAAGAGGG 
                 
               
               
                   
                 
                   ACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATCTGCTCTGG 
                 
               
               
                   
                 
                   TTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGGCTTAT 
                 
               
               
                   
                 
                   ATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTGC 
                 
               
               
                   
                 
                   CAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGC 
                 
               
               
                   
                 
                   CCCACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCT 
                 
               
               
                   
                 
                   CACCAGGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCT 
                 
               
               
                   
                 
                   CTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAA 
                 
               
               
                   
                 
                   CTGGTAAGTACCGCCTATAGACTCTATAGGCACACCCCTTTGGCT 
                 
               
               
                   
                 
                   CTTATGCATGCTGACAGACTAACAGACTGTTCCTTTCCTGGGTCTT 
                 
               
               
                   
                 
                   TTCTGCAGGCCTGTACGGAAGTGTTACTTCTGCTCTAAAAGCTGC 
                 
               
               
                   
                 
                   GGAATTGTACCCGCGGCCGATCCAATCGATACAGATCTAGCGGCC 
                 
               
               
                   
                 
                   GCCCGCCACC 
                   
                     ATGGCTGAGAAAGAGTCAACATCACCACACCTCATG 
                   
                 
               
               
                   
                 
                   
                     GTTCCCATTCTTCTCCTGGTTGGATGGATTGTAGGCTGCATCATCG 
                   
                 
               
               
                   
                 
                   
                     TTATTTACATTGTCTTCTTCTAA 
                   
                   AAGCTTTGGATCCAA 
                   TCAACCTCTG 
                 
               
               
                   
                 
                   GATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTG 
                 
               
               
                   
                 
                   CTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCA 
                 
               
               
                   
                 
                   TGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAA 
                 
               
               
                   
                 
                   TCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGG 
                 
               
               
                   
                 
                   CAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACT 
                 
               
               
                   
                 
                   GGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTC 
                 
               
               
                   
                 
                   GCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGC 
                 
               
               
                   
                 
                   CTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAAT 
                 
               
               
                   
                 
                   TCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTC 
                 
               
               
                   
                 
                   GCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTAC 
                 
               
               
                   
                 
                   GTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTG 
                 
               
               
                   
                 
                   CTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCG 
                   AGATCT 
                   GCCTCGAC 
                 
               
               
                   
                 
                   TGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTG 
                 
               
               
                   
                 
                   CCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAAT 
                 
               
               
                   
                 
                   AAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTAT 
                 
               
               
                   
                 
                   TCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGG 
                 
               
               
                   
                 
                   AAGACAATAGCAGGCATGCTGGGGA 
                   CTCGAGTTAAGGGCAGCCAGAA 
                 
               
               
                   
                 
                   GTCAGATGCTCAAGGGGCTTCATGATGTCCCCATAATTTTTGGCAGAGGGA 
                 
               
               
                   
                 
                   AAAAGATCGGATCCTCAGGCGTAGTTCACCCCGTCCTCGAGGCCGCCCGG 
                 
               
               
                   
                 
                   GTCGACTAAAAAACCTCCCACACCTCCCCCTGAACCTGAAACATAAAATGAA 
                 
               
               
                   
                 
                   TGCAATTGTTGTTGTTA 
                   ACTTGTTTATTGCAGCTTATAATGGTTACAA 
                 
               
               
                   
                 
                   ATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCA 
                 
               
               
                   
                 
                   CTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATC 
                 
               
               
                   
                 
                   ATGTCTGGATC 
                   CGCGCGGCCG 
                   
                     TCAGAAGAACACGATGTAGATCACG 
                   
                 
               
               
                   
                 
                   
                     ATGATGCAGCCGACGATCCAGCCCACCAGCAGCAGAATAGGCACC 
                   
                 
               
               
                   
                 
                   
                     ATCAGGTGGGGGCTGGTAGATTCCTTCTCGGCCAT 
                   
                   GGTGGCGGCTA 
                 
               
               
                   
                 
                   GCCTATAGTGAGTCGTATTA 
                   AGTACTCTAGCCTTAAGAGCTGTAATTG 
                 
               
               
                   
                 
                   AACTGGGAGTGGACACCTGTGGAGAGAAAGGCAAAGTGGATGTC 
                 
               
               
                   
                 
                   AGTAAGACCAATAGGTGCCTATCAGAAACGCAAGAGTCTTCTCTG 
                 
               
               
                   
                 
                   TCTCGACAAGCCCAGTTTCTATTGGTCTCCTTAAACCTGTCTTGTA 
                 
               
               
                   
                 
                   ACCTTGATACTTACCTGCCCAGTGCCTCACGACCAACTTCTGCAGC 
                 
               
               
                   
                 
                   TTAAGTTCGAGACTGTTGTGTCAGAAGCACTGACTGCGTTAGCAA 
                 
               
               
                   
                 
                   TTTAACTGTGATAAACTACCGCAATAAAGCTCTAGAGCTTCGGGG 
                 
               
               
                   
                 
                   ATCGTCCCACGGAGCGGTGGGTGCCGGCGGCTGTCTGGGAAGGG 
                 
               
               
                   
                 
                   CTCCTTGGGGGGCAGAGGCTTTAAGGTCCCCCCGGCGCCCACCCC 
                 
               
               
                   
                 
                   GGGGCGGGCAGAGCCAGCAGGAATGTGCCCGGCGCCCAGAGAGG 
                 
               
               
                   
                 
                   AATGCAACACTTGTGAGCTGCTATTTTGGCAGCAGCGGCCCCGGC 
                 
               
               
                   
                 
                   CCCCTCCGTGCTCCCCCTTCCCCCACAGGAGCCCATATAAGCCCA 
                 
               
               
                   
                 
                   AGCTATTGTGTGGCCTCAGAGTTTTGCTATTTTAAACCCGTCGGAC 
                 
               
               
                   
                 
                   GGAGATACGTGAGTGCCCGAGGGGCTGACACAAGCCAGCCAGCT 
                 
               
               
                   
                 
                   GTCACCTCCCAGGGCTGGGGACGCTGATAAGGCAGCGCTTCGGAC 
                 
               
               
                   
                 
                   CCGACCCTCTGCCGCAGCCCCAGATGCTGTCATGTGAAAGCCCAG 
                 
               
               
                   
                 
                   ACTGCTTTTATCCCTGCTTGGACTTCTAATGCTGTGCTTTTCCTTC 
                 
               
               
                   
                 
                   AGTTCACACCAGTTAAAAATAGAAAACTGGGCACCGGCATCTCTG 
                 
               
               
                   
                 
                   TCTAGAGTGGGCTTGGATTGATATGCTGAGCAGGACTGCTGATTA 
                 
               
               
                   
                 
                   TCTTCAGGGGCCGGGCAGTGCTGGGTCCTCCCCTCAGAGCTTCTC 
                 
               
               
                   
                 
                   AACCATGTTTGGGATGGTCTAGGGATGAAACTGCTGGACAGCTGA 
                 
               
               
                   
                 
                   GCCATGGAGACTGGGGAGAGGCCTGCCTGGCTGAGACCAAGCCC 
                 
               
               
                   
                 
                   TGCTGTACCATCTGCATTTGACAGTGAGGATGCCCATTGACAGGA 
                 
               
               
                   
                 
                   AGCAGACGTAGAGAAAAGGAGAATCAGAATGATCGACAGGCTTCA 
                 
               
               
                   
                 
                   AATCCTACCTCTAACACTTAACTACGTTCCGCACGTTTGGTCTCGG 
                 
               
               
                   
                   GCAGGCCAGTT G AATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTA   
               
               
                   
                 
                   GATAAGTAGCATGGCGGGTTAATCATTAACTACA 
                   AGGAACCCCTAGTGA 
                 
               
               
                   
                 
                   TGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGG 
                 
               
               
                   
                 
                   CCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCG 
                 
               
               
                   
                   GCCTCAGTGAGCGAGCGAGCGCGCAG  (SEQ ID NO: 55) 
               
               
                   
               
               
                 pHZ33 
                 
                   CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGG 
                 
               
               
                 distinct sequence elements 
                 
                   GCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAG 
                 
               
               
                 are indicated in bold, 
                 
                   CGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT 
                   TGT 
                 
               
               
                 starting with ITR, 
                 
                   AGTTAATGATTAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAA 
                 
               
               
                 promoter/enhancer combo 
                 
                   GATCGGAATTCGCCCTTAAG 
                   CCTTCAGATTAAAAATAACTAAGGTAAG 
                 
               
               
                 (αMHCe, followed by 
                 
                   GGCCATGTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCC 
                 
               
               
                 hcTnTp), DWORF (which 
                 
                   TCTATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGG 
                 
               
               
                 is also underlined), WPRE, 
                 
                   ACTAAAAAAAGGCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACC 
                 
               
               
                 poly A (hGHpA), 
                 
                   TTTCATGGGCAAACCTCAGGGCTGCTGTCGTCATGGAGAAGACCC 
                 
               
               
                 promoter/enhancer combo 
                 
                   ACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGC 
                 
               
               
                 (ACTC1e, followed by 
                 
                   CTAAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTC 
                 
               
               
                 ccTnTp), optimized 
                 
                   TTTACCCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGC 
                 
               
               
                 DWORF (which is also 
                 
                   CCTCTGCCTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTG 
                 
               
               
                 underlined), SV40pA, ITR 
                 
                   GAGGTTGCCTTCTGCCCCCCAAGCCTGCTCCCAGCTGGCCCTCCC 
                 
               
               
                   
                 
                   AGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGATTCTCAAGAGGG 
                 
               
               
                   
                 
                   ACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATCTGCTCTGG 
                 
               
               
                   
                 
                   TTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGGCTTAT 
                 
               
               
                   
                 
                   ATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTGC 
                 
               
               
                   
                 
                   CAAAATAGCAGCCAAGACCCCCCACCCCCACCGCCATCCCCCTGC 
                 
               
               
                   
                 
                   CCCACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCT 
                 
               
               
                   
                 
                   CACCAGGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCT 
                 
               
               
                   
                 
                   CTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAA 
                 
               
               
                   
                 
                   CTGGTAAGTACCGCCTATAGACTCTATAGGCACACCCCTTTGGCT 
                 
               
               
                   
                 
                   CTTATGCATGCTGACAGACTAACAGACTGTTCCTTTCCTGGGTCTT 
                 
               
               
                   
                 
                   TTCTGCAGGCCTGTACGGAAGTGTTACTTCTGCTCTAAAAGCTGC 
                 
               
               
                   
                 
                   GGAATTGTACCCGCGGCCGATCCAATCGATACAGATCTAGCGGCC 
                 
               
               
                   
                 
                   GCCCGCCACC 
                   
                     ATGGCTGAGAAAGAGTCAACATCACCACACCTCATG 
                   
                 
               
               
                   
                 
                   
                     GTTCCCATTCTTCTCCTGGTTGGATGGATTGTAGGCTGCATCATCG 
                   
                 
               
               
                   
                 
                   
                     TTATTTACATTGTCTTCTTCTAA 
                   
                   AAGCTTTGGATCCAA 
                   TCAACCTCTG 
                 
               
               
                   
                 
                   GATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTG 
                 
               
               
                   
                 
                   CTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCA 
                 
               
               
                   
                 
                   TGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAA 
                 
               
               
                   
                 
                   TCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGG 
                 
               
               
                   
                 
                   CAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACT 
                 
               
               
                   
                 
                   GGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTC 
                 
               
               
                   
                 
                   GCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGC 
                 
               
               
                   
                 
                   CTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAAT 
                 
               
               
                   
                 
                   TCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTC 
                 
               
               
                   
                 
                   GCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTAC 
                 
               
               
                   
                 
                   GTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTG 
                 
               
               
                   
                 
                   CTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCG 
                   AGATCT 
                   GCCTCGAC 
                 
               
               
                   
                 
                   TGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTG 
                 
               
               
                   
                 
                   CCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAAT 
                 
               
               
                   
                 
                   AAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTAT 
                 
               
               
                   
                 
                   TCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGG 
                 
               
               
                   
                 
                   AAGACAATAGCAGGCATGCTGGGGA 
                   CTCGAGTTAAGGGCAGCCAGAA 
                 
               
               
                   
                 
                   GTCAGATGCTCAAGGGGCTTCATGATGTCCCCATAATTTTTGGCAGAGGGA 
                 
               
               
                   
                 
                   AAAAGATCGGATCCTCAGGCGTAGTTCACCCCGTCCTCGAGGCCGCCCGG 
                 
               
               
                   
                 
                   GTCGACTAAAAAACCTCCCACACCTCCCCCTGAACCTGAAACATAAAATGAA 
                 
               
               
                   
                 
                   TGCAATTGTTGTTGTTA 
                   AACTGGCCTGCCCGAGACCAAACGTGCGGA 
                 
               
               
                   
                 
                   ACGTAGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATT 
                 
               
               
                   
                 
                   CTGATTCTCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCT 
                 
               
               
                   
                 
                   CACTGTCAAATGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGG 
                 
               
               
                   
                 
                   CAGGCCTCTCCCCAGTCTCCATGGCTCAGCTGTCCAGCAGTTTCA 
                 
               
               
                   
                 
                   TCCCTAGACCATCCCAAAGATGGTTGAGAAGCTCTGAGGGGAGGA 
                 
               
               
                   
                 
                   CCCAGCACTGCCCGGCCCCTGAAGATAATCAGCAGTCCTGCTCAG 
                 
               
               
                   
                 
                   CATATCAATCCAAGCCCACTCTAGACAGAGATGCCGGTGCCCAGT 
                 
               
               
                   
                 
                   TTTCTATTTTTAACTGGTGTGAACTGAAGGAAAAGCACAGCATTAG 
                 
               
               
                   
                 
                   AAGTCCAAGCAGGGATAAAAGCAGTCTGGGCTTTCACATGACAGC 
                 
               
               
                   
                 
                   ATCTGGGGCTGCGGCAGAGGGTCGGGTCCGAAGCGCTGCCTTATC 
                 
               
               
                   
                 
                   AGCGTCCCCAGCCCTGGGAGGTGACAGCTGGCTGGCTTGTGTCAG 
                 
               
               
                   
                 
                   CCCCTCGGGCACTCACGTATCTCCGTCCGACGGGTTTAAAATAGC 
                 
               
               
                   
                 
                   AAAACTCTGAGGCCACACAATAGCTTGGGCTTATATGGGCTCCTG 
                 
               
               
                   
                 
                   TGGGGGAAGGGGGAGCACGGAGGGGGCCGGGGCCGCTGCTGCCA 
                 
               
               
                   
                 
                   AAATAGCAGCTCACAAGTGTTGCATTCCTCTCTGGGCGCCGGGCA 
                 
               
               
                   
                 
                   CATTCCTGGTGGCTCTGCCCGCCCCGGGGTGGGGGCCGGGGGGA 
                 
               
               
                   
                 
                   CCTTAAAGCCTCTGCCCCCCAAGGAGCCCTTCCCAGACAGCCGCC 
                 
               
               
                   
                 
                   GGCACCCACCGCTCCGTGGGACGATCCCCGAAGCTCTAGAGCTTT 
                 
               
               
                   
                 
                   ATTGCGGTAGTTTATCACAGTTAAATTGCTAACGCAGTCAGTGCTT 
                 
               
               
                   
                 
                   CTGACACAACAGTCTCGAACTTAAGCTGCAGAAGTTGGTCGTGAG 
                 
               
               
                   
                 
                   GCACTGGGCAGGTAAGTATCAAGGTTACAAGACAGGTTTAAGGAG 
                 
               
               
                   
                 
                   ACCAATAGAAACTGGGCTTGTCGAGACAGAGAAGACTCTTGCGTT 
                 
               
               
                   
                 
                   TCTGATAGGCACCTATTGGTCTTACTGACATCCACTTTGCCTTTCT 
                 
               
               
                   
                 
                   CTCCACAGGTGTCCACTCCCAGTTCAATTACAGCTCTTAAGGCTAG 
                 
               
               
                   
                 
                   AGTACT 
                   TAATACGACTCACTATAGGCTAGCCGCCACC 
                   
                     ATGGCCGAGAAG 
                   
                 
               
               
                   
                 
                   
                     GAATCTACCAGCCCCCACCTGATGGTGCCTATTCTGCTGCTGGTG 
                   
                 
               
               
                   
                 
                   
                     GGCTGGATCGTCGGCTGCATCATCGTGATCTACATCGTGTTCTTCT 
                   
                 
               
               
                   
                 
                   
                     GA 
                   
                   CGGCCGCGCG 
                   GATCCAGACATGATAAGATACATTGATGAGTTTG 
                 
               
               
                   
                 
                   GACAAACCACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTG 
                 
               
               
                   
                 
                   AAATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCTGCAA 
                 
               
               
                   
                 
                   TAAACAAGT 
                   GAATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGA 
                 
               
               
                   
                 
                   TAAGTAGCATGGCGGGTTAATCATTAACTACA 
                   AGGAACCCCTAGTGATG 
                 
               
               
                   
                 
                   GAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCC 
                 
               
               
                   
                 
                   GGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGC 
                 
               
               
                   
                   CTCAGTGAGCGAGCGAGCGCGCAG  (SEQ ID NO: 56) 
               
               
                   
               
               
                 pHZ34 
                 
                   CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGG 
                 
               
               
                 distinct sequence elements 
                 
                   GCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAG 
                 
               
               
                 are indicated in bold, 
                 
                   CGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT 
                   TGT 
                 
               
               
                 starting with ITR, poly A 
                 
                   AGTTAATGATTAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAA 
                 
               
               
                 (hGHpA), WPRE, DWORF 
                 
                   GATCGGAATTC 
                   TCCCCAGCATGCCTGCTATTGTCTTCCCAATCCTCC 
                 
               
               
                 (which is also underlined), 
                 
                   CCCTTGCTGTCCTGCCCCACCCCACCCCCCAGAATAGAATGACAC 
                 
               
               
                 promoter/enhancer combo 
                 
                   CTACTCAGACAATGCGATGCAATTTCCTCATTTTATTAGGAAAGGA 
                 
               
               
                 (hcTnTp followed by 
                 
                   CAGTGGGAGTGGCACCTTCCAGGGTCAAGGAAGGCACGGGGGAG 
                 
               
               
                 αMHCe, followed by 
                 
                   GGGCAAACAACAGATGGCTGGCAACTAGAAGGCACAGTCGAGGC 
                   A 
                 
               
               
                 ACTC1e, followed by 
                 
                   GATCT 
                   CGAAGACGCGGAAGAGGCCGCAGAGCCGGCAGCAGGCCGC 
                 
               
               
                 ccTnTp), optimized 
                 
                   GGGAAGGAAGGTCCGCTGGATTGAGGGCCGAAGGGACGTAGCAG 
                 
               
               
                 DWORF (which is also 
                 
                   AAGGACGTCCCGCGCAGAATCCAGGTGGCAACACAGGCGAGCAG 
                 
               
               
                 underlined), SV40pA, ITR 
                 
                   CCAAGGAAAGGACGATGATTTCCCCGACAACACCACGGAATTGTC 
                 
               
               
                   
                 
                   AGTGCCCAACAGCCGAGCCCCTGTCCAGCAGCGGGCAAGGCAGG 
                 
               
               
                   
                 
                   CGGCGATGAGTTCCGCCGTGGCAATAGGGAGGGGGAAAGCGAAA 
                 
               
               
                   
                 
                   GTCCCGGAAAGGAGCTGACAGGTGGTGGCAATGCCCCAACCAGT 
                 
               
               
                   
                 
                   GGGGGTTGCGTCAGCAAACACAGTGCACACCACGCCACGTTGCCT 
                 
               
               
                   
                 
                   GACAACGGGCCACAACTCCTCATAAAGAGACAGCAACCAGGATTT 
                 
               
               
                   
                 
                   ATACAAGGAGGAGAAAATGAAAGCCATACGGGAAGCAATAGCATG 
                 
               
               
                   
                 
                   ATACAAAGGCATTAAAGCAGCGTATCCACATAGCGTAAAAGGAGC 
                 
               
               
                   
                 
                   AACATAGTTAAGAATACCAGTCAATCTTTCACAAATTTTGTAATCC 
                 
               
               
                   
                 
                   AGAGGTTGA 
                   TTGGATCCAAAGCTT 
                   
                     TTAGAAGAAGACAATGTAAATAA 
                   
                 
               
               
                   
                 
                   
                     CGATGATGCAGCCTACAATCCATCCAACCAGGAGAAGAATGGGAA 
                   
                 
               
               
                   
                 
                   
                     CCATGAGGTGTGGTGATGTTGACTCTTTCTCAGCCAT 
                   
                   GGTGGCGGG 
                 
               
               
                   
                 
                   C 
                   GGCCGCTAGATCTGTATCGATTGGATCGGCCGCGGGTACAATTC 
                 
               
               
                   
                 
                   CGCAGCTTTTAGAGCAGAAGTAACACTTCCGTACAGGCCTGCAGA 
                 
               
               
                   
                 
                   AAAGACCCAGGAAAGGAACAGTCTGTTAGTCTGTCAGCATGCATA 
                 
               
               
                   
                 
                   AGAGCCAAAGGGGTGTGCCTATAGAGTCTATAGGCGGTACTTACC 
                 
               
               
                   
                 
                   AGTTATGGAGGCGTCTGCTCAGTCTCAGCGGGGACTGGGTGAGGC 
                 
               
               
                   
                 
                   AGAGGATGGAGAGGGCTTTAAGCAGGCATGTGGGCTGGGGCCTG 
                 
               
               
                   
                 
                   GTGAGCCAGCCCTGCGGAGGGAGGAATGTGCGACAGGGGACGGG 
                 
               
               
                   
                 
                   TGGGGCAGGGGGATGGCGGTGGGGGTGGGGGGTGTTGGCTGCTA 
                 
               
               
                   
                 
                   TTTTGGCAGGTGCCAGGGACAAGGCTACAGGAACATGTACCCCAC 
                 
               
               
                   
                 
                   GCCATATAAGCCCATGTGGTCCTCCAGCTGCTCAGATAAGCTATTT 
                 
               
               
                   
                 
                   AAAACCAGAGCAGATATGCAGGGAACAGTCATGCAACATAAACCA 
                 
               
               
                   
                 
                   GCTGTCCCTCTTGAGAATCCTGATAAAGCAGAGGCCAGCAACCCA 
                 
               
               
                   
                 
                   GGCCTGGGAGGGCCAGCTGGGAGCAGGGTTGGGGGGCAGAAGGC 
                 
               
               
                   
                 
                   AACCTCCAAGACACTCCATAAGTCTCAGCACCAGAATCTTGGAAG 
                 
               
               
                   
                 
                   GCAGAGGGCAAGAGTTATGTGCTGCTCCACTTGAACTGATGCTGG 
                 
               
               
                   
                 
                   GGGTAAAGACATCTTCCAGGCTACTGGCTCCTAATGGACTGAGCA 
                 
               
               
                   
                 
                   GCCTTAGGCAGGTTGCCGGCTCTGCCAGCCCCAGTGAGGACATCT 
                 
               
               
                   
                 
                   GCAAGGTGGGTCTTCTCCATGACGACAGCAGCCCTGAGGTTTGCC 
                 
               
               
                   
                 
                   CATGAAAGGTCTGCTGCCCTCGCCCCTCTGGCTCCAGGGCCTTTT 
                 
               
               
                   
                 
                   TTTAGTCCTTGGGCACATTCCTCCTCCCCAAAGGGCCGATGGGCA 
                 
               
               
                   
                 
                   GATAGAGGAGAGACAGGACCGTCTCACACCACCTCCCCTACCCAC 
                 
               
               
                   
                 
                   ATGGCCCTTACCTTAGTTATTTTTAATCTGAAGG 
                   CTCGAGTTAAGGG 
                 
               
               
                   
                 
                   CAGCCAGAAGTCAGATGCTCAAGGGGCTTCATGATGTCCCCATAATTTTTG 
                 
               
               
                   
                 
                   GCAGAGGGAAAAAGATCGGATCCTCAGGCGTAGTTCACCCCGTCCTCGAG 
                 
               
               
                   
                 
                   GCCGCCCGGGTCGACTAAAAAACCTCCCACACCTCCCCCTGAACCTGAAAC 
                 
               
               
                   
                 
                   ATAAAATGAATGCAATTGTTGTTGTTA 
                   AACTGGCCTGCCCGAGACCAAA 
                 
               
               
                   
                 
                   CGTGCGGAACGTAGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGT 
                 
               
               
                   
                 
                   CGATCATTCTGATTCTCCTTTTCTCTACGTCTGCTTCCTGTCAATG 
                 
               
               
                   
                 
                   GGCATCCTCACTGTCAAATGCAGATGGTACAGCAGGGCTTGGTCT 
                 
               
               
                   
                 
                   CAGCCAGGCAGGCCTCTCCCCAGTCTCCATGGCTCAGCTGTCCAG 
                 
               
               
                   
                 
                   CAGTTTCATCCCTAGACCATCCCAAACATGGTTGAGAAGCTCTGA 
                 
               
               
                   
                 
                   GGGGAGGACCCAGCACTGCCCGGCCCCTGAAGATAATCAGCAGTC 
                 
               
               
                   
                 
                   CTGCTCAGCATATCAATCCAAGCCCACTCTAGACAGAGATGCCGG 
                 
               
               
                   
                 
                   TGCCCAGTTTTCTATTTTTAACTGGTGTGAACTGAAGGAAAAGCAC 
                 
               
               
                   
                 
                   AGCATTAGAAGTCCAAGCAGGGATAAAAGCAGTCTGGGCTTTCAC 
                 
               
               
                   
                 
                   ATGACAGCATCTGGGGCTGCGGCAGAGGGTCGGGTCCGAAGCGC 
                 
               
               
                   
                 
                   TGCCTTATCAGCGTCCCCAGCCCTGGGAGGTGACAGCTGGCTGGC 
                 
               
               
                   
                 
                   TTGTGTCAGCCCCTCGGGCACTCACGTATCTCCGTCCGACGGGTT 
                 
               
               
                   
                 
                   TAAAATAGCAAAACTCTGAGGCCACACAATAGCTTGGGCTTATAT 
                 
               
               
                   
                 
                   GGGCTCCTGTGGGGGAAGGGGGAGCACGGAGGGGGCCGGGGCC 
                 
               
               
                   
                 
                   GCTGCTGCCAAAATAGCAGCTCACAAGTGTTGCATTCCTCTCTGG 
                 
               
               
                   
                 
                   GCGCCGGGCACATTCCTGCTGGCTCTGCCCGCCCCGGGGTGGGC 
                 
               
               
                   
                 
                   GCCGGGGGGACCTTAAAGCCTCTGCCCCCCAAGGAGCCCTTCCCA 
                 
               
               
                   
                 
                   GACAGCCGCCGGCACCCACCGCTCCGTGGGACGATCCCCGAAGCT 
                 
               
               
                   
                 
                   CTAGAGCTTTATTGCGGTAGTTTATCACAGTTAAATTGCTAACGCA 
                 
               
               
                   
                 
                   GTCAGTGCTTCTGACACAACAGTCTCGAACTTAAGCTGCAGAAGT 
                 
               
               
                   
                 
                   TGGTCGTGAGGCACTGGGCAGGTAAGTATCAAGGTTACAAGACAG 
                 
               
               
                   
                 
                   GTTTAAGGAGACCAATAGAAACTGGGCTTGTCGAGACAGAGAAGA 
                 
               
               
                   
                 
                   CTCTTGCGTTTCTGATAGGCACCTATTGGTCTTACTGACATCCACT 
                 
               
               
                   
                 
                   TTGCCTTTCTCTCCACAGGTGTCCACTCCCAGTTCAATTACAGCTC 
                 
               
               
                   
                 
                   TTAAGGCTAGAGTACT 
                   TAATACGACTCACTATAGGCTAGCCGCCACC 
                   
                     AT 
                   
                 
               
               
                   
                 
                   
                     GGCCGAGAAGGAATCTACCAGCCCCCACCTGATGGTGCCTATTCT 
                   
                 
               
               
                   
                 
                   
                     GCTGCTGGTGGGCTGGATCGTCGGCTGCATCATCGTGATCTACAT 
                   
                 
               
               
                   
                 
                   
                     CGTGTTCTTCTGA 
                   
                   CGGCCGCGCG 
                   GATCCAGACATGATAAGATACAT 
                 
               
               
                   
                 
                   TGATGAGTTTGGACAAACCACAACTAGAATGCAGTGAAAAAAATG 
                 
               
               
                   
                 
                   CTTTATTTGTGAAATTTGTGATGCTATTGCTTTATTTGTAACCATTA 
                 
               
               
                   
                 
                   TAAGCTGCAATAAACAAGT 
                   GAATTCCCGATTAGGATCTTCCTAGAGCAT 
                 
               
               
                   
                 
                   GGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTAACTACA 
                   AGGAACC 
                 
               
               
                   
                 
                   CCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCT 
                 
               
               
                   
                 
                   CACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTG 
                 
               
               
                   
                   CCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG  (SEQ ID NO: 57) 
               
               
                   
               
               
                 pHZ69 
                 
                   CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGG 
                 
               
               
                 distinct sequence elements 
                 
                   GCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAG 
                 
               
               
                 are indicated in bold, 
                 
                   CGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT 
                   TGT 
                 
               
               
                 starting with ITR, hcTnTp, 
                 
                   AGTTAATGATTAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAA 
                 
               
               
                 DWORF (which is also 
                 
                   GATCGGAATTCGCCCTTAAG 
                   GTCATGGAGAAGACCCACCTTGCAGAT 
                 
               
               
                 underlined), WPRE, poly A 
                 
                   GTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCT 
                 
               
               
                 (hGHpA), SV40pA, 
                 
                   CAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAG 
                 
               
               
                 optimized DWORF (which 
                 
                   CATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGCCTTCC 
                 
               
               
                 is also underlined), ccTnTp, 
                 
                   AAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTT 
                 
               
               
                 ITR 
                 
                   CTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTT 
                 
               
               
                   
                 
                   GCTGGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTT 
                 
               
               
                   
                 
                   ATGTTGCATGACTGTTCCCTGCATATCTGCTCTGGTTTTAAATAGC 
                 
               
               
                   
                 
                   TTATCTGAGCAGCTGGAGGACCACATGGGCTTATATGGCGTGGGG 
                 
               
               
                   
                 
                   TACATGTTCCTGTAGCCTTGTCCCTGGCACCTGCCAAAATAGCAG 
                 
               
               
                   
                 
                   CCAACACCCCCCACCCCCACCGCCATCCCCCTGCCCCACCCGTCC 
                 
               
               
                   
                 
                   CCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCAGGCCCC 
                 
               
               
                   
                 
                   AGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCACCCA 
                 
               
               
                   
                 
                   GTCCCCGCTGAGACTGAGCAGACGCCTCCATAACTGGTAAGTACC 
                 
               
               
                   
                 
                   GCCTATAGACTCTATAGGCACACCCCTTTGGCTCTTATGCATGCTG 
                 
               
               
                   
                 
                   ACAGACTAACAGACTGTTCCTTTCCTGGGTCTTTTCTGCAGGCCTG 
                 
               
               
                   
                 
                   TACGGAAGTGTTACTTCTGCTCTAAAAGCTGCGGAATTGTACCCG 
                 
               
               
                   
                 
                   CGGCCGATCCAATCGATACAGATCTAGCGGCC 
                   GCCCGCCACC 
                   
                     ATGG 
                   
                 
               
               
                   
                 
                   
                     CTGAGAAAGAGTCAACATCACCACACCTCATGGTTCCCATTCTTCT 
                   
                 
               
               
                   
                 
                   
                     CCTGGTTGGATGGATTGTAGGCTGCATCATCGTTATTTACATTGTC 
                   
                 
               
               
                   
                 
                   
                     TTCTTCTA 
                   
                   AAAGCTTTGGATCCAA 
                   TCAACCTCTGGATTACAAAATTTG 
                 
               
               
                   
                 
                   TGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTA 
                 
               
               
                   
                 
                   TGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCC 
                 
               
               
                   
                 
                   GTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTC 
                 
               
               
                   
                 
                   TCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGT 
                 
               
               
                   
                 
                   GTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGC 
                 
               
               
                   
                 
                   CACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCT 
                 
               
               
                   
                 
                   ATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGG 
                 
               
               
                   
                 
                   ACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCG 
                 
               
               
                   
                 
                   GGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCT 
                 
               
               
                   
                 
                   GGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCA 
                 
               
               
                   
                 
                   ATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGC 
                 
               
               
                   
                 
                   CTCTTCCGCGTCTTCG 
                   AGATCT 
                   GCCTCGACTGTGCCTTCTAGTTGC 
                 
               
               
                   
                 
                   CAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGG 
                 
               
               
                   
                 
                   AAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGC 
                 
               
               
                   
                 
                   ATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGT 
                 
               
               
                   
                 
                   GGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGC 
                 
               
               
                   
                 
                   ATGCTGGGGA 
                   CTCGAGTTAAGGGCAGCCAGAAGTCAGATGCTCAAGGGG 
                 
               
               
                   
                 
                   CTTCATGATGTCCCCATAATTTTTGGCAGAGGGAAAAAGATCGGATCCTCAG 
                 
               
               
                   
                 
                   GCGTAGTTCACCCCGTCCTCGAGGCCGCCCGGGTCGACTAAAAAACCTCC 
                 
               
               
                   
                 
                   CACACCTCCCCCTGAACCTGAAACATAAAATGAATGCAATTGTTGTTGTTA 
                   A 
                 
               
               
                   
                 
                   CTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATC 
                 
               
               
                   
                 
                   ACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTG 
                 
               
               
                   
                 
                   GTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGGATC 
                   CGCGC 
                 
               
               
                   
                 
                   GGCCG 
                   
                     TCAGAAGAACACGATGTAGATCACGATGATGCAGCCGACG 
                   
                 
               
               
                   
                 
                   
                     ATCCAGCCCACCAGCAGCAGAATAGGCACCATCAGGTGGGGGCTG 
                   
                 
               
               
                   
                 
                   
                     GTAGATTCCTTCTCGGCCAT 
                   
                   GGTGGCGGCTAGCCTATAGTGAGTCGTA 
                 
               
               
                   
                 
                   TTA 
                   AGTACTCTAGCCTTAAGAGCTGTAATTGAACTGGGAGTGGACA 
                 
               
               
                   
                 
                   CCTGTGGAGAGAAAGGCAAAGTGGATGTCAGTAAGACCAATAGGT 
                 
               
               
                   
                 
                   GCCTATCAGAAACGCAAGAGTCTTCTCTGTCTCGACAAGCCCAGT 
                 
               
               
                   
                 
                   TTCTATTGGTCTCCTTAAACCTGTCTTGTAACCTTGATACTTACCT 
                 
               
               
                   
                 
                   GCCCAGTGCCTCACGACCAACTTCTGCAGCTTAAGTTCGAGACTG 
                 
               
               
                   
                 
                   TTGTGTCAGAAGCACTGACTGCGTTAGCAATTTAACTGTGATAAAC 
                 
               
               
                   
                 
                   TACCGCAATAAAGCTCTAGAGCTTCGGGGATCGTCCCACGGAGCG 
                 
               
               
                   
                 
                   GTGGGTGCCGGCGGCTGTCTGGGAAGGGCTCCTTGGGGGGCAGA 
                 
               
               
                   
                 
                   GGCTTTAAGGTCCCCCCGGCGCCCACCCCGGGGCGGGCAGAGCC 
                 
               
               
                   
                 
                   AGCAGGAATGTGCCCGGCGCCCAGAGAGGAATGCAACACTTGTGA 
                 
               
               
                   
                 
                   GCTGCTATTTTGGCAGCAGCGGCCCCGGCCCCCTCCGTGCTCCCC 
                 
               
               
                   
                 
                   CTTCCCCCACAGGAGCCCATATAAGCCCAAGCTATTGTGTGGCCT 
                 
               
               
                   
                 
                   CAGAGTTTTGCTATTTTAAACCCGTCGGACGGAGATACGTGAGTG 
                 
               
               
                   
                 
                   CCCGAGGGGCTGACACAAGCCAGCCAGCTGTCACCTCCCAGGGCT 
                 
               
               
                   
                 
                   GGGGACGCTGATAAGGCAGCGCTTCGGACCCGACCCTCTGCCGCA 
                 
               
               
                   
                 
                   GCCCCAGATGCTGTCATGTGAAAGCCCAGACTGCTTTTATCCC 
                   GAA 
                 
               
               
                   
                 
                   TTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGCATGGC 
                 
               
               
                   
                 
                   GGGTTAATCATTAACTACA 
                   AGGAACCCCTAGTGATGGAGTTGGCCACT 
                 
               
               
                   
                 
                   CCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAG 
                 
               
               
                   
                 
                   GTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGA 
                 
               
               
                   
                   GCGAGCGCGCAG  (SEQ ID NO: 58) 
               
               
                   
               
               
                 pHZ72 
                 
                   CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGG 
                 
               
               
                 distinct sequence elements 
                 
                   GCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAG 
                 
               
               
                 are indicated in bold, 
                 
                   CGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT 
                   TGT 
                 
               
               
                 starting with ITR, hcTnTp, 
                 
                   AGTTAATGATTAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAA 
                 
               
               
                 DWORF (which is also 
                 
                   GATCGGAATTCGCCCTTAAG 
                   GTCATGGAGAAGACCCACCTTGCAGAT 
                 
               
               
                 underlined), WPRE, poly A 
                 
                   GTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCT 
                 
               
               
                 (hGHpA), ccTnTp, 
                 
                   CAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAG 
                 
               
               
                 optimized DWORF (which 
                 
                   CATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGCCTTCC 
                 
               
               
                 is also underlined), 
                 
                   AAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTT 
                 
               
               
                 SV40pA, ITR 
                 
                   CTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTT 
                 
               
               
                   
                 
                   GCTGGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTT 
                 
               
               
                   
                 
                   ATGTTGCATGACTGTTCCCTGCATATCTGCTCTGGTTTTAAATAGC 
                 
               
               
                   
                 
                   TTATCTGAGCAGCTGGAGGACCACATGGGCTTATATGGCGTGGGG 
                 
               
               
                   
                 
                   TACATGTTCCTGTAGCCTTGTCCCTGGCACCTGCCAAAATAGCAG 
                 
               
               
                   
                 
                   CCAACACCCCCCACCCCCACCGCCATCCCCCTGCCCCACCCGTCC 
                 
               
               
                   
                 
                   CCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCAGGCCCC 
                 
               
               
                   
                 
                   AGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCACCCA 
                 
               
               
                   
                 
                   GTCCCCGCTGAGACTGAGCAGACGCCTCCATAACTGGTAAGTACC 
                 
               
               
                   
                 
                   GCCTATAGACTCTATAGGCACACCCCTTTGGCTCTTATGCATGCTG 
                 
               
               
                   
                 
                   ACAGACTAACAGACTGTTCCTTTCCTGGGTCTTTTCTGCAGGCCTG 
                 
               
               
                   
                 
                   TACGGAAGTGTTACTTCTGCTCTAAAAGCTGCGGAATTGTACCCG 
                 
               
               
                   
                 
                   CGGCCGATCCAATCGATACAGATCTAGCGGCC 
                   GCCCGCCACC 
                   
                     ATGG 
                   
                 
               
               
                   
                 
                   
                     CTGAGAAAGAGTCAACATCACCACACCTCATGGTTCCCATTCTTCT 
                   
                 
               
               
                   
                 
                   
                     CCTGGTTGGATGGATTGTAGGCTGCATCATCGTTATTTACATTGTC 
                   
                 
               
               
                   
                 
                   
                     TTCTTCTAA 
                   
                   AAGCTTTGGATCCAA 
                   TCAACCTCTGGATTACAAAATTTG 
                 
               
               
                   
                 
                   TGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTA 
                 
               
               
                   
                 
                   TGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCC 
                 
               
               
                   
                 
                   GTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTC 
                 
               
               
                   
                 
                   TCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGT 
                 
               
               
                   
                 
                   GTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGC 
                 
               
               
                   
                 
                   CACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCT 
                 
               
               
                   
                 
                   ATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGG 
                 
               
               
                   
                 
                   ACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCG 
                 
               
               
                   
                 
                   GGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCT 
                 
               
               
                   
                 
                   GGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCA 
                 
               
               
                   
                 
                   ATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGC 
                 
               
               
                   
                 
                   CTCTTCCGCGTCTTCG 
                   AGATCT 
                   GCCTCGACTGTGCCTTCTAGTTGC 
                 
               
               
                   
                 
                   CAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGG 
                 
               
               
                   
                 
                   AAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGC 
                 
               
               
                   
                 
                   ATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGT 
                 
               
               
                   
                 
                   GGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGC 
                 
               
               
                   
                 
                   ATGCTGGGGA 
                   CTCGAGTTAAGGGCAGCCAGAAGTCAGATGCTCAAGGGG 
                 
               
               
                   
                 
                   CTTCATGATGTCCCCATAATTTTTGGCAGAGGGAAAAAGATCGGATCCTCAG 
                 
               
               
                   
                 
                   GCGTAGTTCACCCCGTCCTCGAGGCCGCCCGGGTCGACTAAAAAACCTCC 
                 
               
               
                   
                 
                   CACACCTCCCCCTGAACCTGAAACATAAAATGAATGCAATTGTTGTTGTTA 
                   G 
                 
               
               
                   
                 
                   GGATAAAAGCAGTCTGGGCTTTCACATGACAGCATCTGGGGCTGC 
                 
               
               
                   
                 
                   GGCAGAGGGTCGGGTCCGAAGCGCTGCCTTATCAGCGTCCCCAGC 
                 
               
               
                   
                 
                   CCTGGGAGGTGACAGCTGGCTGGCTTGTGTCAGCCCCTCGGGCAC 
                 
               
               
                   
                 
                   TCACGTATCTCCGTCCGACGGGTTTAAAATAGCAAAACTCTGAGG 
                 
               
               
                   
                 
                   CCACACAATAGCTTGGGCTTATATGGGCTCCTGTGGGGGAAGGGG 
                 
               
               
                   
                 
                   GAGCACGGAGGGGGCCGGGGCCGCTGCTGCCAAAATAGCAGCTC 
                 
               
               
                   
                 
                   ACAAGTGTTGCATTCCTCTCTGGGCGCCGGGCACATTCCTGCTGG 
                 
               
               
                   
                 
                   CTCTGCCCGCCCCGGGGTGGGCGCCGGGGGGACCTTAAAGCCTC 
                 
               
               
                   
                 
                   TGCCCCCCAAGGAGCCCTTCCCAGACAGCCGCCGGCACCCACCGC 
                 
               
               
                   
                 
                   TCCGTGGGACGATCCCCGAAGCTCTAGAGCTTTATTGCGGTAGTT 
                 
               
               
                   
                 
                   TATCACAGTTAAATTGCTAACGCAGTCAGTGCTTCTGACACAACAG 
                 
               
               
                   
                 
                   TCTCGAACTTAAGCTGCAGAAGTTGGTCGTGAGGCACTGGGCAGG 
                 
               
               
                   
                 
                   TAAGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAAC 
                 
               
               
                   
                 
                   TGGGCTTGTCGAGACAGAGAAGACTCTTGCGTTTCTGATAGGCAC 
                 
               
               
                   
                 
                   CTATTGGTCTTACTGACATCCACTTTGCCTTTCTCTCCACAGGTGT 
                 
               
               
                   
                 
                   CCACTCCCAGTTCAATTACAGCTCTTAAGGCTAGAGTACT 
                   TAATACG 
                 
               
               
                   
                 
                   ACTCACTATAGGCTAGCCGCCACC 
                   
                     ATGGCCGAGAAGGAATCTACCAGC 
                   
                 
               
               
                   
                 
                   
                     CCCCACCTGATGGTGCCTATTCTGCTGCTGGTGGGCTGGATCGTC 
                   
                 
               
               
                   
                 
                   
                     GGCTGCATCATCGTGATCTACATCGTGTTCTTCTGA 
                   
                   CGGCCGCGCG 
                 
               
               
                   
                 
                   GATCCAGACATGATAAGATACATTGATGAGTTTGGACAAACCACA 
                 
               
               
                   
                 
                   ACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAAATTTGTGATG 
                 
               
               
                   
                 
                   CTATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACAAGT 
                   GAAT 
                 
               
               
                   
                 
                   TCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGCATGGCG 
                 
               
               
                   
                 
                   GGTTAATCATTAACTACA 
                   AGGAACCCCTAGTGATGGAGTTGGCCACTC 
                 
               
               
                   
                 
                   CCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGG 
                 
               
               
                   
                 
                   TCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAG 
                 
               
               
                   
                   CGAGCGCGCAG  (SEQ ID NO: 59) 
               
               
                   
               
               
                 pHZ75 
                 
                   CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGG 
                 
               
               
                 distinct sequence elements 
                 
                   GCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAG 
                 
               
               
                 are indicated in bold, 
                 
                   CGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT 
                   TGT 
                 
               
               
                 starting with ITR, poly A 
                 
                   AGTTAATGATTAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAA 
                 
               
               
                 (hGHpA), WPRE, 
                 
                   GATCGGAATTC 
                   TCCCCAGCATGCCTGCTATTGTCTTCCCAATCCTCC 
                 
               
               
                 DWORF (which is also 
                 
                   CCCTTGCTGTCCTGCCCCACCCCACCCCCCAGAATAGAATGACAC 
                 
               
               
                 underlined), hcTnTp/ 
                 
                   CTACTCAGACAATGCGATGCAATTTCCTCATTTTATTAGGAAAGGA 
                 
               
               
                 ccTnTp combo, optimized 
                 
                   CAGTGGGAGTGGCACCTTCCAGGGTCAAGGAAGGCACGGGGGAG 
                 
               
               
                 DWORF (which is also 
                 
                   GGGCAAACAACAGATGGCTGGCAACTAGAAGGCACAGTCGAGGC 
                   A 
                 
               
               
                 underlined), SV40pA, ITR 
                 
                   GATCT 
                   CGAAGACGCGGAAGAGGCCGCAGAGCCGGCAGCAGGCCGC 
                 
               
               
                   
                 
                   GGGAAGGAAGGTCCGCTGGATTGAGGGCCGAAGGGACGTAGCAG 
                 
               
               
                   
                 
                   AAGGACGTCCCGCGCAGAATCCAGGTGGCAACACAGGCGAGCAG 
                 
               
               
                   
                 
                   CCAAGGAAAGGACGATGATTTCCCCGACAACACCACGGAATTGTC 
                 
               
               
                   
                 
                   AGTGCCCAACAGCCGAGCCCCTGTCCAGCAGCGGGCAAGGCAGG 
                 
               
               
                   
                 
                   CGGCGATGAGTTCCGCCGTGGCAATAGGGAGGGGGAAAGCGAAA 
                 
               
               
                   
                 
                   GTCCCGGAAAGGAGCTGACAGGTGGTGGCAATGCCCCAACCAGT 
                 
               
               
                   
                 
                   GGGGGTTGCGTCAGCAAACACAGTGCACACCACGCCACGTTGCCT 
                 
               
               
                   
                 
                   GACAACGGGCCACAACTCCTCATAAAGAGACAGCAACCAGGATTT 
                 
               
               
                   
                 
                   ATACAAGGAGGAGAAAATGAAAGCCATACGGGAAGCAATAGCATG 
                 
               
               
                   
                 
                   ATACAAAGGCATTAAAGCAGCGTATCCACATAGCGTAAAAGGAGC 
                 
               
               
                   
                 
                   AACATAGTTAAGAATACCAGTCAATCTTTCACAAATTTTGTAATCC 
                 
               
               
                   
                 
                   AGAGGTTGA 
                   TTGGATCCAAAGCTT 
                   
                     TTAGAAGAAGACAATGTAAATAA 
                   
                 
               
               
                   
                 
                   
                     CGATGATGCAGCCTACAATCCATCCAACCAGGAGAAGAATGGGAA 
                   
                 
               
               
                   
                 
                   
                     CCATGAGGTGTGGTGATGTTGACTCTTTCTCAGCCATGGTGGCGG 
                   
                 
               
               
                   
                 
                   GCGGCCGC 
                   TAGATCTGTATCGATTGGATCGGCCGCGGGTACAATTC 
                 
               
               
                   
                 
                   CGCAGCTTTTAGAGCAGAAGTAACACTTCCGTACAGGCCTGCAGA 
                 
               
               
                   
                 
                   AAAGACCCAGGAAAGGAACAGTCTGTTAGTCTGTCAGCATGCATA 
                 
               
               
                   
                 
                   AGAGCCAAAGGGGTGTGCCTATAGAGTCTATAGGCGGTACTTACC 
                 
               
               
                   
                 
                   AGTTATGGAGGCGTCTGCTCAGTCTCAGCGGGGACTGGGTGAGGC 
                 
               
               
                   
                 
                   AGAGGATGGAGAGGGCTTTAAGCAGGCATGTGGGCTGGGGCCTG 
                 
               
               
                   
                 
                   GTGAGCCAGCCCTGCGGAGGGAGGAATGTGCGACAGGGGACGGG 
                 
               
               
                   
                 
                   TGGGGCAGGGGGATGGCGGTGGGGGTGGGGGGTGTTGGCTGCTA 
                 
               
               
                   
                 
                   TTTTGGCAGGTGCCAGGGACAAGGCTACAGGAACATGTACCCCAC 
                 
               
               
                   
                 
                   GCCATATAAGCCCATGTGGTCCTCCAGCTGCTCAGATAAGCTATTT 
                 
               
               
                   
                 
                   AAAACCAGAGCAGATATGCAGGGAACAGTCATGCAACATAAACCA 
                 
               
               
                   
                 
                   GCTGTCCCTCTTGAGAATCCTGATAAAGCAGAGGCCAGCAACCCA 
                 
               
               
                   
                 
                   GGCCTGGGAGGGCCAGCTGGGAGCAGGGTTGGGGGGCAGAAGGC 
                 
               
               
                   
                 
                   AACCTCCAAGACACTCCATAAGTCTCAGCACCAGAATCTTGGAAG 
                 
               
               
                   
                 
                   GCAGAGGGCAAGAGTTATGTGCTGCTCCACTTGAACTGATGCTGG 
                 
               
               
                   
                 
                   GGGTAAAGACATCTTCCAGGCTACTGGCTCCTAATGGACTGAGCA 
                 
               
               
                   
                 
                   GCCTTAGGCAGGTTGCCGGCTCTGCCAGCCCCAGTGAGGACATCT 
                 
               
               
                   
                 
                   GCAAGGTGGGTCTTCTCCATGAC 
                   CTCGAGTTAAGGGCAGCCAGAAGTC 
                 
               
               
                   
                 
                   AGATGCTCAAGGGGCTTCATGATGTCCCCATAATTTTTGGCAGAGGGAAAA 
                 
               
               
                   
                 
                   AGATCGGATCCTCAGGCGTAGTTCACCCCGTCCTCGAGGCCGCCCGGGTC 
                 
               
               
                   
                 
                   GACTAAAAAACCTCCCACACCTCCCCCTGAACCTGAAACATAAAATGAATGC 
                 
               
               
                   
                 
                   AATTGTTGTTGTTA 
                   GGGATAAAAGCAGTCTGGGCTTTCACATGACAG 
                 
               
               
                   
                 
                   CATCTGGGGCTGCGGCAGAGGGTCGGGTCCGAAGCGCTGCCTTAT 
                 
               
               
                   
                 
                   CAGCGTCCCCAGCCCTGGGAGGTGACAGCTGGCTGGCTTGTGTCA 
                 
               
               
                   
                 
                   GCCCCTCGGGCACTCACGTATCTCCGTCCGACGGGTTTAAAATAG 
                 
               
               
                   
                 
                   CAAAACTCTGAGGCCACACAATAGCTTGGGCTTATATGGGCTCCT 
                 
               
               
                   
                 
                   GTGGGGGAAGGGGGAGCACGGAGGGGGCCGGGGCCGCTGCTGC 
                 
               
               
                   
                 
                   CAAAATAGCAGCTCACAAGTGTTGCATTCCTCTCTGGGCGCCGGG 
                 
               
               
                   
                 
                   CACATTCCTGCTGGCTCTGCCCGCCCCGGGGTGGGCGCCGGGGG 
                 
               
               
                   
                 
                   GACCTTAAAGCCTCTGCCCCCCAAGGAGCCCTTCCCAGACAGCCG 
                 
               
               
                   
                 
                   CCGGCACCCACCGCTCCGTGGGA 
                   CGATCCCCGAAGCTCTAGAGCTTTA 
                 
               
               
                   
                 
                   TTGCGGTAGTTTATCACAGTTAAATTGCTAACGCAGTCAGTGCTTCTGACAC 
                 
               
               
                   
                 
                   AACAGTCTCGAACTTAAGCTGCAGAAGTTGGTCGTGAGGCACTGGGCAGGT 
                 
               
               
                   
                 
                   AAGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCTT 
                 
               
               
                   
                 
                   GTCGAGACAGAGAAGACTCTTGCGTTTCTGATAGGCACCTATTGGTCTTACT 
                 
               
               
                   
                 
                   GACATCCACTTTGCCTTTCTCTCCACAGGTGTCCACTCCCAGTTCAATTACA 
                 
               
               
                   
                 
                   GCTCTTAAGGCTAGAGTACTTAATACGACTCACTATAGGCTAGCCGCCACC 
                 
               
               
                   
                 
                   
                     ATGGCCGAGAAGGAATCTACCAGCCCCCACCTGATGGTGCCTATT 
                   
                 
               
               
                   
                 
                   
                     CTGCTGCTGGTGGGCTGGATCGTCGGCTGCATCATCGTGATCTAC 
                   
                 
               
               
                   
                 
                   
                     ATCGTGTTCTTCTGA 
                   
                   CGGCCGCGCG 
                   GATCCAGACATGATAAGATAC 
                 
               
               
                   
                 
                   ATTGATGAGTTTGGACAAACCACAACTAGAATGCAGTGAAAAAAA 
                 
               
               
                   
                 
                   TGCTTTATTTGTGAAATTTGTGATGCTATTGCTTTATTTGTAACCA 
                 
               
               
                   
                   TTATAAGCTGCAATAAACAAGT GAATTCCCGATTAGGATCTTCCTAG 
               
               
                   
                 AGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTAACTACA 
               
               
                   
                 
                   AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTC 
                 
               
               
                   
                 
                   GCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCG 
                 
               
               
                   
                 
                   GGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
                 
               
               
                   
                 (SEQ ID NO: 60) 
               
               
                   
               
               
                 pHZ51 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ15) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGAACTGGCCTGCCCGAGACCAAACGTGCGGAACGT 
               
               
                   
                 AGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATTCTGATTC 
               
               
                   
                 TCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACTGTCAAA 
               
               
                   
                 TGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCTCTCCCC 
               
               
                   
                 AGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCATCCCA 
               
               
                   
                 AACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCC 
               
               
                   
                 CTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTC 
               
               
                   
                 TAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACT 
               
               
                   
                 GAAGGAAAAGCACAGCATTAGAAGTCCAAGCAGTCATGGAGAAGACC 
               
               
                   
                 CACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCT 
               
               
                   
                 AAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTAC 
               
               
                   
                 CCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGCC 
               
               
                   
                 TTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTT 
               
               
                   
                 CTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCT 
               
               
                   
                 GGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTG 
               
               
                   
                 CATGACTGTTCCCTGCATATCTGCTCTGGTTTTAAATAGCTTATCTGAG 
               
               
                   
                 CAGCTGGAGGACCACATGGGCTTATATGGCGTGGGGTACATGTTCCTG 
               
               
                   
                 TAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCACC 
               
               
                   
                 CCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCC 
               
               
                   
                 TCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGC 
               
               
                   
                 CCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACG 
               
               
                   
                 CCTCCAGCGGCCGCCCGCCACCATGGCTGAAAAAGCGGGGTCTACATT 
               
               
                   
                 TTCACACCTTCTGGTTCCTATTCTTCTCCTGATTGGCTGGATTGTGGGC 
               
               
                   
                 TGCATCATAATGATTTATGTTGTCTTCTCTTAGAAGCTTTGGATCCAAT 
               
               
                   
                 CAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAAC 
               
               
                   
                 TATGTTGCTCCTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGT 
               
               
                   
                 ATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAA 
               
               
                   
                 TCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAAC 
               
               
                   
                 GTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGG 
               
               
                   
                 GCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCT 
               
               
                   
                 CCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTG 
               
               
                   
                 GACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGG 
               
               
                   
                 GAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCTGGATT 
               
               
                   
                 CTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCG 
               
               
                   
                 GACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTC 
               
               
                   
                 TTCGAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTT 
               
               
                   
                 TGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTG 
               
               
                   
                 TCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGT 
               
               
                   
                 GTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAG 
               
               
                   
                 GATTGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGTTAAGGGCG 
               
               
                   
                 AATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGC 
               
               
                   
                 ATGGCGGGTTAATCATTAACTACAAGGAACCCCTAGTGATGGAGTTGG 
               
               
                   
                 CCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAA 
               
               
                   
                 AGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGC 
               
               
                   
                 GAGCGCGCAG (SEQ ID NO: 61) 
               
               
                   
               
               
                 pHZ100 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ72) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGGTCATGGAGAAGACCCACCTTGCAGATGTCCTCA 
               
               
                   
                 CTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATTA 
               
               
                   
                 GGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAGT 
               
               
                   
                 GGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAACTGGTAAGTACC 
               
               
                   
                 GCCTATAGACTCTATAGGCACACCCCTTTGGCTCTTATGCATGCTGACA 
               
               
                   
                 GACTAACAGACTGTTCCTTTCCTGGGTCTTTTCTGCAGGCCTGTACGGA 
               
               
                   
                 AGTGTTACTTCTGCTCTAAAAGCTGCGGAATTGTACCCGCGGCCGATC 
               
               
                   
                 CAATCGATACAGATCTAGCGGCCGCCCGCCACCATGGCTGAAAAAGC 
               
               
                   
                 GGGGTCTACATTTTCACACCTTCTGGTTCCTATTCTTCTCCTGATTGGCT 
               
               
                   
                 GGATTGTGGGCTGCATCATAATGATTTATGTTGTCTTCTCTTAGAAGCT 
               
               
                   
                 TTGGATCCAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTG 
               
               
                   
                 GTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTT 
               
               
                   
                 AATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCT 
               
               
                   
                 CCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGT 
               
               
                   
                 TGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCC 
               
               
                   
                 CACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTC 
               
               
                   
                 GCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTG 
               
               
                   
                 CCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGG 
               
               
                   
                 TGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGC 
               
               
                   
                 CACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTC 
               
               
                   
                 AATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCT 
               
               
                   
                 CTTCCGCGTCTTCGAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCC 
               
               
                   
                 ATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCC 
               
               
                   
                 ACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTC 
               
               
                   
                 TGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCA 
               
               
                   
                 AGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGT 
               
               
                   
                 TAAGGGCAGCCAGAAGTCAGATGCTCAAGGGGCTTCATGATGTCCCCA 
               
               
                   
                 TAATTTTTGGCAGAGGGAAAAAGATCGGATCCTCAGGCGTAGTTCACC 
               
               
                   
                 CCGTCCTCGAGGCCGCCCGGGTCGACTAAAAAACCTCCCACACCTCCC 
               
               
                   
                 CCTGAACCTGAAACATAAAATGAATGCAATTGTTGTTGTTAGGGATAA 
               
               
                   
                 AAGCAGTCTGGGCTTTCACATGACAGCATCTGGGGCTGCGGCAGAGG 
               
               
                   
                 GTCGGGTCCGAAGCGCTGCCTTATCAGCGTCCCCAGCCCTGGGAGGTG 
               
               
                   
                 ACAGCTGGCTGGCTTGTGTCAGCCCCTCGGGCACTCACGTATCTCCGT 
               
               
                   
                 CCGACGGGTTTAAAATAGCAAAACTCTGAGGCCACACAATAGCTTGG 
               
               
                   
                 GCTTATATGGGCTCCTGTGGGGGAAGGGGGAGCACGGAGGGGGCCGG 
               
               
                   
                 GGCCGCTGCTGCCAAAATAGCAGCTCACAAGTGTTGCATTCCTCTCTG 
               
               
                   
                 GGCGCCGGGCACATTCCTGCTGGCTCTGCCCGCCCCGGGGTGGGCGCC 
               
               
                   
                 GGGGGGACCTTAAAGCCTCTGCCCCCCAAGGAGCCCTTCCCAGACAGC 
               
               
                   
                 CGCCGGCACCCACCGCTCCGTGGGACGATCCCCGAAGCTCTAGAGCTT 
               
               
                   
                 TATTGCGGTAGTTTATCACAGTTAAATTGCTAACGCAGTCAGTGCTTCT 
               
               
                   
                 GACACAACAGTCTCGAACTTAAGCTGCAGAAGTTGGTCGTGAGGCACT 
               
               
                   
                 GGGCAGGTAAGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATA 
               
               
                   
                 GAAACTGGGCTTGTCGAGACAGAGAAGACTCTTGCGTTTCTGATAGGC 
               
               
                   
                 ACCTATTGGTCTTACTGACATCCACTTTGCCTTTCTCTCCACAGGTGTC 
               
               
                   
                 CACTCCCAGTTCAATTACAGCTCTTAAGGCTAGAGTACTTAATACGAC 
               
               
                   
                 TCACTATAGGCTAGCCGCCACCATGGCCGAGAAGGCCGGATCTACCTT 
               
               
                   
                 CAGCCACCTGCTGGTCCCTATTCTGCTGCTGATCGGCTGGATCGTGGG 
               
               
                   
                 CTGCATCATCATGATCTACGTGGTGTTCAGCTGACGGCCGCGCGGATC 
               
               
                   
                 CAGACATGATAAGATACATTGATGAGTTTGGACAAACCACAACTAGA 
               
               
                   
                 ATGCAGTGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCTATTGCTT 
               
               
                   
                 TATTTGTAACCATTATAAGCTGCAATAAACAAGTGAATTCCCGATTAG 
               
               
                   
                 GATCTTCCTAGAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAAT 
               
               
                   
                 CATTAACTACAAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCT 
               
               
                   
                 GCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGAC 
               
               
                   
                 GCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 (SEQ ID NO: 62) 
               
               
                   
               
               
                 pHZ101 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ75) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCTCCCCAGCATGCCTGCTATTGTCTTCCCAATCCTCCCCCTTGCT 
               
               
                   
                 CTCCTGCCCCACCCCACCCCCCAGAATAGAATGACACCTACTCAGACA 
               
               
                   
                 ATGCGATGCAATTTCCTCATTTTATTAGGAAAGGACAGTGGGAGTGGC 
               
               
                   
                 ACCTTCCAGGGTCAAGGAAGGCACGGGGGAGGGGCAAACAACAGATG 
               
               
                   
                 CCTGGCAACTAGAAGGCACAGTCGAGGCAGATCTCGAAGACGCGGAA 
               
               
                   
                 GAGGCCGCAGAGCCGGCAGCAGGCCGCGGGAAGGAAGGTCCGCTGGA 
               
               
                   
                 TTGAGGGCCGAAGGGACGTAGCAGAAGGACGTCCCGCGCAGAATCCA 
               
               
                   
                 GGTGGCAACACAGGCGAGCAGCCAAGGAAAGGACGATGATTTCCCCG 
               
               
                   
                 ACAACACCACGGAATTGTCAGTGCCCAACAGCCGAGCCCCTGTCCAGC 
               
               
                   
                 AGCGGGCAAGGCAGGCGGCGATGAGTTCCGCCGTGGCAATAGGGAGG 
               
               
                   
                 GGGAAAGCGAAAGTCCCGGAAAGGAGCTGACAGGTGGTGGCAATGCC 
               
               
                   
                 CCAACCAGTGGGGGTTGCGTCAGCAAACACAGTGCACACCACGCCAC 
               
               
                   
                 GTTGCCTGACAACGGGCCACAACTCCTCATAAAGAGACAGCAACCAG 
               
               
                   
                 GATTTATACAAGGAGGAGAAAATGAAAGCCATACGGGAAGCAATAGC 
               
               
                   
                 ATGATACAAAGGCATTAAAGCAGCGTATCCACATAGCGTAAAAGGAG 
               
               
                   
                 CAACATAGTTAAGAATACCAGTCAATCTTTCACAAATTTTGTAATCCA 
               
               
                   
                 GAGGTTGATTGGATCCAAAGCTTCTAAGAGAAGACAACATAAATCATT 
               
               
                   
                 ATGATGCAGCCCACAATCCAGCCAATCAGGAGAAGAATAGGAACCAG 
               
               
                   
                 AAGGTGTGAAAATGTAGACCCCGCTTTTTCAGCCATGGTGGCGGGCGG 
               
               
                   
                 CCGCTAGATCTGTATCGATTGGATCGGCCGCGGGTACAATTCCGCAGC 
               
               
                   
                 TTTTAGAGCAGAAGTAACACTTCCGTACAGGCCTGCAGAAAAGACCCA 
               
               
                   
                 GGAAAGGAACAGTCTGTTAGTCTGTCAGCATGCATAAGAGCCAAAGG 
               
               
                   
                 GGTGTGCCTATAGAGTCTATAGGCGGTACTTACCAGTTATGGAGGCGT 
               
               
                   
                 CTGCTCAGTCTCAGCGGGGACTGGGTGAGGCAGAGGATGGAGAGGGC 
               
               
                   
                 TTTAAGCAGGCATGTGGGCTGGGGCCTGGTGAGCCAGCCCTGCGGAG 
               
               
                   
                 GGAGGAATGTGCGACAGGGGACGGGTGGGGCAGGGGGATGGCGGTG 
               
               
                   
                 GGGGTGGGGGGTGTTGGCTGCTATTTTGGCAGGTGCCAGGGACAAGG 
               
               
                   
                 CTACAGGAACATGTACCCCACGCCATATAAGCCCATGTGGTCCTCCAG 
               
               
                   
                 CTGCTCAGATAAGCTATTTAAAACCAGAGCAGATATGCAGGGAACAG 
               
               
                   
                 TCATGCAACATAAACCAGCTGTCCCTCTTGAGAATCCTGATAAAGCAG 
               
               
                   
                 AGGCCAGCAACCCAGGCCTGGGAGGGCCAGCTGGGAGCAGGGTTGGG 
               
               
                   
                 GGGCAGAAGGCAACCTCCAAGACACTCCATAAGTCTCAGCACCAGAA 
               
               
                   
                 TCTTGGAAGGCAGAGGGCAAGAGTTATGTGCTGCTCCACTTGAACTGA 
               
               
                   
                 TGCTGGGGGTAAAGACATCTTCCAGGCTACTGGCTCCTAATGGACTGA 
               
               
                   
                 GCAGCCTTAGGCAGGTTGCCGGCTCTGCCAGCCCCAGTGAGGACATCT 
               
               
                   
                 GCAAGGTGGGTCTTCTCCATGACCTCGAGTTAAGGGCAGCCAGAAGTC 
               
               
                   
                 AGATGCTCAAGGGGCTTCATGATGTCCCCATAATTTTTGGCAGAGGGA 
               
               
                   
                 AAAAGATCGGATCCTCAGGCGTAGTTCACCCCGTCCTCGAGGCCGCCC 
               
               
                   
                 GGCTCGACTAAAAAACCTCCCACACCTCCCCCTGAACCTGAAACATAA 
               
               
                   
                 AATGAATGCAATTGTTGTTGTTAGGGATAAAAGCAGTCTGGGCTTTCA 
               
               
                   
                 CATGACAGCATCTGGGGCTGCGGCAGAGGGTCGGGTCCGAAGCGCTG 
               
               
                   
                 CCTTATCAGCGTCCCCAGCCCTGGGAGGTGACAGCTGGCTGGCTTGTG 
               
               
                   
                 TCAGCCCCTCGGGCACTCACGTATCTCCGTCCGACGGGTTTAAAATAG 
               
               
                   
                 CAAAACTCTGAGGCCACACAATAGCTTGGGCTTATATGGGCTCCTGTG 
               
               
                   
                 GGGGAAGGGGGAGCACGGAGGGGGCCGGGGCCGCTGCTGCCAAAAT 
               
               
                   
                 AGCAGCTCACAAGTGTTGCATTCCTCTCTGGGCGCCGGGCACATTCCT 
               
               
                   
                 GCTGGCTCTGCCCGCCCCGGGGTGGGCGCCGGGGGGACCTTAAAGCCT 
               
               
                   
                 CTGCCCCCCAAGGAGCCCTTCCCAGACAGCCGCCGGCACCCACCGCTC 
               
               
                   
                 CGTGGGACGATCCCCGAAGCTCTAGAGCTTTATTGCGGTAGTTTATCA 
               
               
                   
                 CAGTTAAATTGCTAACGCAGTCAGTGCTTCTGACACAACAGTCTCGAA 
               
               
                   
                 CTTAAGCTGCAGAAGTTGGTCGTGAGGCACTGGGCAGGTAAGTATCAA 
               
               
                   
                 GGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGCTTGTCGA 
               
               
                   
                 GACAGAGAAGACTCTTGCGTTTCTGATAGGCACCTATTGGTCTTACTG 
               
               
                   
                 ACATCCACTTTGCCTTTCTCTCCACAGGTGTCCACTCCCAGTTCAATTA 
               
               
                   
                 CAGCTCTTAAGGCTAGAGTACTTAATACGACTCACTATAGGCTAGCCG 
               
               
                   
                 CCACCATGGCCGAGAAGGCCGGATCTACCTTCAGCCACCTGCTGGTCC 
               
               
                   
                 CTATTCTGCTGCTGATCGGCTGGATCGTGGGCTGCATCATCATGATCTA 
               
               
                   
                 CGTGGTGTTCAGCTGACGGCCGCGCGGATCCAGACATGATAAGATACA 
               
               
                   
                 TTGATGAGTTTGGACAAACCACAACTAGAATGCAGTGAAAAAAATGC 
               
               
                   
                 TTTATTTGTGAAATTTGTGATGCTATTGCTTTATTTGTAACCATTATAA 
               
               
                   
                 GCTGCAATAAACAAGTGAATTCCCGATTAGGATCTTCCTAGAGCATGG 
               
               
                   
                 CTACGTAGATAAGTAGCATGGCGGGTTAATCATTAACTACAAGGAACC 
               
               
                   
                 CCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACT 
               
               
                   
                 GAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGC 
               
               
                   
                 GGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID NO: 63) 
               
               
                   
               
               
                 pHZ52 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ16) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGAACTGGCCTGCCCGAGACCAAACGTGCGGAACGT 
               
               
                   
                 AGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATTCTGATTC 
               
               
                   
                 TCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACTGTCAAA 
               
               
                   
                 TGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCTCTCCCC 
               
               
                   
                 AGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCATCCCA 
               
               
                   
                 AACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCC 
               
               
                   
                 CTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTC 
               
               
                   
                 TAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACT 
               
               
                   
                 GAAGGAAAAGCACAGCATTAGAAGTCCAAGCACCTTCAGATTAAAAA 
               
               
                   
                 TAACTAAGGTAAGGGCCATGTGGGTAGGGGAGGTGGTGTGAGACGGT 
               
               
                   
                 CCTGTCTCTCCTCTATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTG 
               
               
                   
                 CCCAAGGACTAAAAAAAGGCCCTGGAGCCAGAGGGGCGAGGGCAGC 
               
               
                   
                 AGACCTTTCATGGGCAAACCTCAGGGCTGCTGTCGTCATGGAGAAGAC 
               
               
                   
                 CCACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCC 
               
               
                   
                 TAAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTA 
               
               
                   
                 CCCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGC 
               
               
                   
                 CTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCT 
               
               
                   
                 TCTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCT 
               
               
                   
                 GGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTG 
               
               
                   
                 CATGACTGTTCCCTGCATATCTGCTCTGGTTTTAAATAGCTTATCTGAG 
               
               
                   
                 CAGCTGGAGGACCACATGGGCTTATATGGCGTGGGGTACATGTTCCTG 
               
               
                   
                 TAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCACC 
               
               
                   
                 CCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCC 
               
               
                   
                 TCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGC 
               
               
                   
                 CCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACG 
               
               
                   
                 CCTCCAGCGGCCGCCCGCCACCATGGCTGAAAAAGCGGGGTCTACATT 
               
               
                   
                 TTCACACCTTCTGGTTCCTATTCTTCTCCTGATTGGCTGGATTGTGGGC 
               
               
                   
                 TGCATCATAATGATTTATGTTGTCTTCTCTTAGAAGCTTTGGATCCAAT 
               
               
                   
                 CAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAAC 
               
               
                   
                 TATGTTGCTCCTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGT 
               
               
                   
                 ATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAA 
               
               
                   
                 TCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAAC 
               
               
                   
                 GTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGG 
               
               
                   
                 GCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCT 
               
               
                   
                 CCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTG 
               
               
                   
                 GACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGG 
               
               
                   
                 GAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCTGGATT 
               
               
                   
                 CTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCG 
               
               
                   
                 GACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTC 
               
               
                   
                 TTCGAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTT 
               
               
                   
                 TGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTG 
               
               
                   
                 TCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGT 
               
               
                   
                 GTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAG 
               
               
                   
                 GATTGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGTTAAGGGCG 
               
               
                   
                 AATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGC 
               
               
                   
                 ATGGCGGGTTAATCATTAACTACAAGGAACCCCTAGTGATGGAGTTGG 
               
               
                   
                 CCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAA 
               
               
                   
                 AGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGC 
               
               
                   
                 GAGCGCGCAG (SEQ ID NO: 64) 
               
               
                   
               
               
                 pHZ53 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ17) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGCCTTCAGATTAAAAATAACTAAGGTAAGGGCCAT 
               
               
                   
                 GTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCCTCTATCTGC 
               
               
                   
                 CCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAAAAAAAG 
               
               
                   
                 GCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTTCATGGGCAAAC 
               
               
                   
                 CTCAGGGCTGCTGTCGTCATGGAGAAGACCCACCTTGCAGATGTCCTC 
               
               
                   
                 ACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATT 
               
               
                   
                 AGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAG 
               
               
                   
                 TGGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCAGCGGCCGCCCGCCAC 
               
               
                   
                 CATGGCTGAAAAAGCGGGGTCTACATTTTCACACCTTCTGGTTCCTATT 
               
               
                   
                 CTTCTCCTGATTGGCTGGATTGTGGGCTGCATCATAATGATTTATGTTG 
               
               
                   
                 TCTTCTCTTAGAAGCTTTGGATCCAATCAACCTCTGGATTACAAAATTT 
               
               
                   
                 GTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTATG 
               
               
                   
                 TGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTATG 
               
               
                   
                 GCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGA 
               
               
                   
                 GGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTT 
               
               
                   
                 TGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGCT 
               
               
                   
                 CCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTC 
               
               
                   
                 ATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGC 
               
               
                   
                 ACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTGGC 
               
               
                   
                 TGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTA 
               
               
                   
                 CGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTG 
               
               
                   
                 CCGGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCTGCCTCGACTGTGCC 
               
               
                   
                 TTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTG 
               
               
                   
                 ACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAA 
               
               
                   
                 ATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGG 
               
               
                   
                 GTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGC 
               
               
                   
                 ATGCTGGGGACTCGAGTTAAGGGCGAATTCCCGATTAGGATCTTCCTA 
               
               
                   
                 GAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTAACTAC 
               
               
                   
                 AAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGC 
               
               
                   
                 TCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTT 
               
               
                   
                 GCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID NO: 65) 
               
               
                   
               
               
                 pHZ54 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ18) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGCCTTCAGATTAAAAATAACTAAGGTAAGGGCCAT 
               
               
                   
                 GTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCCTCTATCTGC 
               
               
                   
                 CCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAAAAAAAG 
               
               
                   
                 GCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTTCATGGGCAAAC 
               
               
                   
                 CTCAGGGCTGCTGTCAACTGGCCTGCCCGAGACCAAACGTGCGGAACG 
               
               
                   
                 TACTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATTCTGATT 
               
               
                   
                 CTCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACTGTCAA 
               
               
                   
                 ATGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCTCTCCC 
               
               
                   
                 CAGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCATCCCA 
               
               
                   
                 AACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCC 
               
               
                   
                 CTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTC 
               
               
                   
                 TAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACT 
               
               
                   
                 GAAGGAAAAGCACAGCATTAGAAGTCCAAGCAGTCATGGAGAAGACC 
               
               
                   
                 CACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCT 
               
               
                   
                 AAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTAC 
               
               
                   
                 CCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGCC 
               
               
                   
                 TTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTT 
               
               
                   
                 CTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCT 
               
               
                   
                 GGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTG 
               
               
                   
                 CATGACTGTTCCCTGCATATCTGCTCTGGTTTAAATAGCTTATCTGAG 
               
               
                   
                 CAGCTGGAGGACCACATGGGCTTATATGGCGTGGGGTACATGTTCCTG 
               
               
                   
                 TAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCACC 
               
               
                   
                 CCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCC 
               
               
                   
                 TCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGC 
               
               
                   
                 CCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACG 
               
               
                   
                 CCTCCAGCGGCCGCCCGCCACCATGGCTGAAAAAGCGGGGTCTACATT 
               
               
                   
                 TTCACACCTTCTGGTTCCTATTCTTCTCCTGATTGGCTGGATTGTGGGC 
               
               
                   
                 TGCATCATAATGATTTATGTTGTCTTCTCTTAGAAGCTTTGGATCCAAT 
               
               
                   
                 CAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAAC 
               
               
                   
                 TATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGT 
               
               
                   
                 ATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAA 
               
               
                   
                 TCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAAC 
               
               
                   
                 GTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGG 
               
               
                   
                 GCATTGCCACGACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCT 
               
               
                   
                 CCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTG 
               
               
                   
                 GACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGG 
               
               
                   
                 GAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCTGGATT 
               
               
                   
                 CTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCAGCG 
               
               
                   
                 GACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTC 
               
               
                   
                 TTCGAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTT 
               
               
                   
                 TGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTG 
               
               
                   
                 TCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGT 
               
               
                   
                 GTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAG 
               
               
                   
                 GATTGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGTTAAGGGCG 
               
               
                   
                 AATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGATAAGTAGC 
               
               
                   
                 ATGGCGGGTTAATCATTAACTACAAGGAACCCCTAGTGATGGAGTTGG 
               
               
                   
                 CCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAA 
               
               
                   
                 AGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGC 
               
               
                   
                 GAGCGCGCAG (SEQ ID NO: 66) 
               
               
                   
               
               
                 pHZ55 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ19) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGCCTTCAGATTAAAAATAACTAAGGTAAGGGCCAT 
               
               
                   
                 GTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCCTCTATCTGC 
               
               
                   
                 CCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAAAAAAAG 
               
               
                   
                 GCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTTCATGGGCAAAC 
               
               
                   
                 CTCAGGGCTGCTGTCAACTGGCCTGCCCGAGACCAAACGTGCGGAACG 
               
               
                   
                 TAGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATTCTGATT 
               
               
                   
                 CTCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACTGTCAA 
               
               
                   
                 ATGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCTCTCCC 
               
               
                   
                 CAGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCATCCCA 
               
               
                   
                 AACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCC 
               
               
                   
                 CTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTC 
               
               
                   
                 TAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACT 
               
               
                   
                 GAAGGAAAAGCACAGCATTAGAAGTCCAAGCAGTCATGGAGAAGACC 
               
               
                   
                 CACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCCT 
               
               
                   
                 AAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTAC 
               
               
                   
                 CCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGCC 
               
               
                   
                 TTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCTT 
               
               
                   
                 CTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCT 
               
               
                   
                 GGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTG 
               
               
                   
                 CATGACTGTTCCCTGCATATCTGCTCTGGTTTTAAATAGCTTATCTGAG 
               
               
                   
                 CAGCTGGAGGACCACATGGGCTTATATGGCGTGGGGTACATGTTCCTG 
               
               
                   
                 TAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCACC 
               
               
                   
                 CCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCC 
               
               
                   
                 TCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGC 
               
               
                   
                 CCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACG 
               
               
                   
                 CCTCCATAACTGGTAAGTACCGCCTATAGACTCTATAGGCACACCCCT 
               
               
                   
                 TTGGCTCTTATGCATGCTGACAGACTAACAGACTGTTCCTTTCCTGGGT 
               
               
                   
                 CTTTTCTGCAGGCCTGTACGGAAGTGTTACTTCTGCTCTAAAAGCTGCG 
               
               
                   
                 GAATTGTACCCGCGGCCGATCCAATCGATACAGATCTAGCGGCCGCCC 
               
               
                   
                 GCCACCATGGCTGAAAAAGCGGGGTCTACATTTTCACACCTTCTGGTT 
               
               
                   
                 CCTATTCTTCTCCTGATTGGCTGGATTGTGGGCTGCATCATAATGATTT 
               
               
                   
                 ATGTTGTCTTCTCTTAGAAGCTTTGGATCCAATCAACCTCTGGATTACA 
               
               
                   
                 AAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTAC 
               
               
                   
                 GCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCC 
               
               
                   
                 CGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCT 
               
               
                   
                 TTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCAC 
               
               
                   
                 TGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTG 
               
               
                   
                 TCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCG 
               
               
                   
                 GAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTG 
               
               
                   
                 TTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTC 
               
               
                   
                 CTTGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTT 
               
               
                   
                 CTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGC 
               
               
                   
                 CTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCTGCCTCGAC 
               
               
                   
                 TGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCT 
               
               
                   
                 TCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATG 
               
               
                   
                 AGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGG 
               
               
                   
                 GTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAG 
               
               
                   
                 CAGGCATGCTGGGGACTCGAGTTAAGGGCGAATTCCCGATTAGGATCT 
               
               
                   
                 TCCTAGAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTA 
               
               
                   
                 ACTACAAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCG 
               
               
                   
                 CTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGG 
               
               
                   
                 GCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID 
               
               
                   
                 NO: 67) 
               
               
                   
               
               
                 pHZ56 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ20) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGGTCATGGAGAAGACCCACCTTGCAGATGTCCTCA 
               
               
                   
                 CTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATTA 
               
               
                   
                 GGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAGT 
               
               
                   
                 GGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAACTGGTAAGTACC 
               
               
                   
                 GCCTATAGACTCTATAGGCACACCCCTTTGGCTCTTATGCATGCTGACA 
               
               
                   
                 GACTAACAGACTGTTCCTTTCCTGGGTCTTTTCTGCAGGCCTGTACGGA 
               
               
                   
                 AGTGTTACTTCTGCTCTAAAAGCTGCGGAATTGTACCCGCGGCCGATC 
               
               
                   
                 CAATCGATACAGATCTAGCGGCCGCCCGCCACCATGGCTGAAAAAGC 
               
               
                   
                 GGGGTCTACATTTTCACACCTTCTGGTTCCTATTCTTCTCCTGATTGGCT 
               
               
                   
                 GGATTGTGGGCTGCATCATAATGATTTATGTTGTCTTCTCTTAGAAGCT 
               
               
                   
                 TTGGATCCAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTG 
               
               
                   
                 GTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTT 
               
               
                   
                 AATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCT 
               
               
                   
                 CCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGT 
               
               
                   
                 TGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCC 
               
               
                   
                 CACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTC 
               
               
                   
                 GCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTG 
               
               
                   
                 CCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGG 
               
               
                   
                 TGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGC 
               
               
                   
                 CACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTC 
               
               
                   
                 AATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCT 
               
               
                   
                 CTTCCGCGTCTTCGAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCC 
               
               
                   
                 ATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCC 
               
               
                   
                 ACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTC 
               
               
                   
                 TGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCA 
               
               
                   
                 AGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGT 
               
               
                   
                 TAAGGGCGAATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGA 
               
               
                   
                 TAAGTAGCATGGCGGGTTAATCATTAACTACAAGGAACCCCTAGTGAT 
               
               
                   
                 GGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGG 
               
               
                   
                 GCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGT 
               
               
                   
                 GAGCGAGCGAGCGCGCAG (SEQ ID NO: 68) 
               
               
                   
               
               
                 pHZ57 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ21) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGAACTGGCCTGCCCGAGACCAAACGTGCGGAACGT 
               
               
                   
                 AGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATTCTGATTC 
               
               
                   
                 TCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACTGTCAAA 
               
               
                   
                 TGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCTCTCCCC 
               
               
                   
                 AGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCATCCCA 
               
               
                   
                 AACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCC 
               
               
                   
                 CTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTC 
               
               
                   
                 TAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACT 
               
               
                   
                 GAAGGAAAAGCACAGCATTAGAAGTCCAAGCACCTTCAGATTAAAAA 
               
               
                   
                 TAACTAAGGTAAGGGCCATGTGGGTAGGGGAGGTGGTGTGAGACGGT 
               
               
                   
                 CCTGTCTCTCCTCTATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTG 
               
               
                   
                 CCCAAGGACTAAAAAAAGGCCCTGGAGCCAGAGGGGCGAGGGCAGC 
               
               
                   
                 AGACCTTTCATGGGCAAACCTCAGGGCTGCTGTCGTCATGGAGAAGAC 
               
               
                   
                 CCACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCC 
               
               
                   
                 TAAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTA 
               
               
                   
                 CCCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGC 
               
               
                   
                 CTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCT 
               
               
                   
                 TCTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCT 
               
               
                   
                 GGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTG 
               
               
                   
                 CATGACTGTTCCCTGCATATCTGCTCTGGTTTTAAATAGCTTATCTGAG 
               
               
                   
                 CAGCTGGAGGACCACATGGGCTTATATGGCGTGGGGTACATGTTCCTG 
               
               
                   
                 TAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCACC 
               
               
                   
                 CCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCC 
               
               
                   
                 TCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGC 
               
               
                   
                 CCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACG 
               
               
                   
                 CCTCCATAACTGGTAAGTACCGCCTATAGACTCTATAGGCACACCCCT 
               
               
                   
                 TTGGCTCTTATGCATGCTGACAGACTAACAGACTGTTCCTTTCCTGGGT 
               
               
                   
                 CTTTTCTGCAGGCCTGTACGGAAGTGTTACTTCTGCTCTAAAAGCTGCG 
               
               
                   
                 GAATTGTACCCGCGGCCGATCCAATCGATACAGATCTAGCGGCCGCCC 
               
               
                   
                 GCCACCATGGCTGAAAAAGCGGGGTCTACATTTTCACACCTTCTGGTT 
               
               
                   
                 CCTATTCTTCTCCTGATTGGCTGGATTGTGGGCTGCATCATAATGATTT 
               
               
                   
                 ATGTTGTCTTCTCTTAGAAGCTTTGGATCCAATCAACCTCTGGATTACA 
               
               
                   
                 AAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTAC 
               
               
                   
                 GCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCC 
               
               
                   
                 CGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCT 
               
               
                   
                 TTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCAC 
               
               
                   
                 TGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTG 
               
               
                   
                 TCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCG 
               
               
                   
                 GAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTG 
               
               
                   
                 TTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTC 
               
               
                   
                 CTTGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTT 
               
               
                   
                 CTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGC 
               
               
                   
                 CTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCTGCCTCGAC 
               
               
                   
                 TGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCT 
               
               
                   
                 TCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATG 
               
               
                   
                 AGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGG 
               
               
                   
                 GTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAG 
               
               
                   
                 CAGGCATGCTGGGGACTCGAGTTAAGGGCGAATTCCCGATTAGGATCT 
               
               
                   
                 TCCTAGAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTA 
               
               
                   
                 ACTACAAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCG 
               
               
                   
                 CTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGG 
               
               
                   
                 GCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID 
               
               
                   
                 NO: 69) 
               
               
                   
               
               
                 pHZ58 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ22) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGAACTGGCCTGCCCGAGACCAAACGTGCGGAACGT 
               
               
                   
                 AGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATTCTGATTC 
               
               
                   
                 TCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACTGTCAAA 
               
               
                   
                 TGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCTCTCCCC 
               
               
                   
                 AGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCATCCCA 
               
               
                   
                 AACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCCGGCCC 
               
               
                   
                 CTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCCCACTC 
               
               
                   
                 TAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGTGAACT 
               
               
                   
                 GAAGGAAAAGCACAGCATTAGAAGTCCAAGCACCTTCAGATTAAAAA 
               
               
                   
                 TAACTAAGGTAAGGGCCATGTGGGTAGGGGAGGTGGTGTGAGACGGT 
               
               
                   
                 CCTGTCTCTCCTCTATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTG 
               
               
                   
                 CCCAAGGACTAAAAAAAGGCCCTGGAGCCAGAGGGGCGAGGGCAGC 
               
               
                   
                 AGACCTTTCATGGGCAAACCTCAGGGCTGCTGTCGTCATGGAGAAGAC 
               
               
                   
                 CCACCTTGCAGATGTCCTCACTGGGGCTGGCAGAGCCGGCAACCTGCC 
               
               
                   
                 TAAGGCTGCTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTA 
               
               
                   
                 CCCCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCTCTGC 
               
               
                   
                 CTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTTGGAGGTTGCCT 
               
               
                   
                 TCTGCCCCCCAACCCTGCTCCCAGCTGGCCCTCCCAGGCCTGGGTTGCT 
               
               
                   
                 GGCCTCTGCTTTATCAGGATTCTCAAGAGGGACAGCTGGTTTATGTTG 
               
               
                   
                 CATGACTGTTCCCTGCATATCTGCTCTGGTTTTAAATAGCTTATCTGAG 
               
               
                   
                 CAGCTGGAGGACCACATGGGCTTATATGGCGTGGGGTACATGTTCCTG 
               
               
                   
                 TAGCCTTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCACC 
               
               
                   
                 CCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACATTCCTCCC 
               
               
                   
                 TCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACATGCCTGCTTAAAGC 
               
               
                   
                 CCTCTCCATCCTCTGCCTCACCCAGTCCCCGCTGAGACTGAGCAGACG 
               
               
                   
                 CCTCCATAACTGGTAAGTACCGCCTATAGACTCTATAGGCACACCCCT 
               
               
                   
                 TTGGCTCTTATGCATGCTGACAGACTAACAGACTGTTCCTTTCCTGGGT 
               
               
                   
                 CTTTTCTGCAGGCCTGTACGGAAGTGTTACTTCTGCTCTAAAAGCTGCG 
               
               
                   
                 GAATTGTACCCGCGGCCGATCCAATCGATACAGATCTAGCGGCCGCCC 
               
               
                   
                 GCCACCATGGCTGAAAAAGCGGGGTCTACATTTTCACACCTTCTGGTT 
               
               
                   
                 CCTATTCTTCTCCTGATTGGCTGGATTGTGGGCTGCATCATAATGATTT 
               
               
                   
                 ATGTTGTCTTCTCTTAGAAGCTTTGGATCCAATCAACCTCTGGATTACA 
               
               
                   
                 AAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTAC 
               
               
                   
                 GCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCC 
               
               
                   
                 CGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCT 
               
               
                   
                 TTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCAC 
               
               
                   
                 TGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTG 
               
               
                   
                 TCAGCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCG 
               
               
                   
                 GAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTG 
               
               
                   
                 TTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTC 
               
               
                   
                 CTTGGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTT 
               
               
                   
                 CTGCTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGC 
               
               
                   
                 CTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCTGCCTCGAC 
               
               
                   
                 TGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCT 
               
               
                   
                 TCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATG 
               
               
                   
                 AGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGG 
               
               
                   
                 GTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAG 
               
               
                   
                 CAGGCATGCTGGGGACTCGAGTTAAGGGCGAATTCCCGATTAGGATCT 
               
               
                   
                 TCCTAGAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTA 
               
               
                   
                 ACTACAAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCG 
               
               
                   
                 CTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGG 
               
               
                   
                 GCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID 
               
               
                   
                 NO: 70) 
               
               
                   
               
               
                 pHZ59 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ23) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGCCTTCAGATTAAAAATAACTAAGGTAAGGGCCAT 
               
               
                   
                 GTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCCTCTATCTGC 
               
               
                   
                 CCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAAAAAAAG 
               
               
                   
                 GCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTTCATGGGCAAAC 
               
               
                   
                 CTCAGGGCTGCTGTCGTCATGGAGAAGACCCACCTTGCAGATGTCCTC 
               
               
                   
                 ACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATT 
               
               
                   
                 AGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAG 
               
               
                   
                 TGGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAACTGGTAAGTACC 
               
               
                   
                 GCCTATAGACTCTATAGGCACACCCCTTTGGCTCTTATGCATGCTGACA 
               
               
                   
                 GACTAACAGACTGTTCCTTTCCTGGGTCTTTTCTGCAGGCCTGTACGGA 
               
               
                   
                 AGTGTTACTTCTGCTCTAAAAGCTGCGGAATTGTACCCGCGGCCGATC 
               
               
                   
                 CAATCGATACAGATCTAGCGGCCGCCCGCCACCATGGCTGAAAAAGC 
               
               
                   
                 GGGGTCTACATTTTCACACCTTCTGGTTCCTATTCTTCTCCTGATTGGCT 
               
               
                   
                 GGATTGTGGGCTGCATCATAATGATTTATGTTGTCTTCTCTTAGAAGCT 
               
               
                   
                 TTGGATCCAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTG 
               
               
                   
                 GTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTT 
               
               
                   
                 AATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCT 
               
               
                   
                 CCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGT 
               
               
                   
                 TGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCC 
               
               
                   
                 CACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTC 
               
               
                   
                 GCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTG 
               
               
                   
                 CCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGG 
               
               
                   
                 TGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGC 
               
               
                   
                 CACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTC 
               
               
                   
                 AATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCT 
               
               
                   
                 CTTCCGCGTCTTCGAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCC 
               
               
                   
                 ATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCC 
               
               
                   
                 ACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTC 
               
               
                   
                 TGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCA 
               
               
                   
                 AGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGT 
               
               
                   
                 TAAGGGCGAATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGA 
               
               
                   
                 TAAGTAGCATGGCGGGTTAATCATTAACTACAAGGAACCCCTAGTGAT 
               
               
                   
                 GGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGG 
               
               
                   
                 GCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGT 
               
               
                   
                 GAGCGAGCGAGCGCGCAG (SEQ ID NO: 71) 
               
               
                   
               
               
                 pHZ60 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ24) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGGTCATGGAGAAGACCCACCTTGCAGATGTCCTCA 
               
               
                   
                 CTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATTA 
               
               
                   
                 GGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAGT 
               
               
                   
                 GGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCAGCGGCCGCCCGCCAC 
               
               
                   
                 CATGGCCGAGAAGGCCGGATCTACCTTCAGCCACCTGCTGGTCCCTAT 
               
               
                   
                 TCTGCTGCTGATCGGCTGGATCGTGGGCTGCATCATCATGATCTACGT 
               
               
                   
                 GGTGTTCAGCTGAAAGCTTTGGATCCAATCAACCTCTGGATTACAAAA 
               
               
                   
                 TTTGTGAAAGATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCT 
               
               
                   
                 ATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGT 
               
               
                   
                 ATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTA 
               
               
                   
                 TGAGGAGTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGT 
               
               
                   
                 GTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTCA 
               
               
                   
                 GCTCCTTTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAA 
               
               
                   
                 CTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTCTTG 
               
               
                   
                 GGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTT 
               
               
                   
                 GGCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTG 
               
               
                   
                 CTACGTCCCTTCGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTG 
               
               
                   
                 CTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGAGATCTGCCTCGACTGT 
               
               
                   
                 GCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCCTGCCTTCC 
               
               
                   
                 TTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAG 
               
               
                   
                 GAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGT 
               
               
                   
                 GGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCA 
               
               
                   
                 GGCATGCTGGGGACTCGAGTTAAGGGCGAATTCCCGATTAGGATCTTC 
               
               
                   
                 CTAGAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTAAC 
               
               
                   
                 TACAAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCT 
               
               
                   
                 CGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGG 
               
               
                   
                 CTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID NO: 
               
               
                   
                 72) 
               
               
                   
               
               
                 pHZ61 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ25) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGCCTTCAGATTAAAAATAACTAAGGTAAGGGCCAT 
               
               
                   
                 GTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCCTCTATCTGC 
               
               
                   
                 CCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAAAAAAAG 
               
               
                   
                 GCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTTCATGGGCAAAC 
               
               
                   
                 CTCAGGGCTGCTGTCGTCATGGAGAAGACCCACCTTGCAGATGTCCTC 
               
               
                   
                 ACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATT 
               
               
                   
                 AGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAG 
               
               
                   
                 TGGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAACTGGTAAGTACC 
               
               
                   
                 GCCTATAGACTCTATAGGCACACCCCTTTGGCTCTTATGCATGCTGACA 
               
               
                   
                 GACTAACAGACTGTTCCTTTCCTGGGTCTTTTCTGCAGGCCTGTACGGA 
               
               
                   
                 AGTGTTACTTCTGCTCTAAAAGCTGCGGAATTGTACCCGCGGCCGATC 
               
               
                   
                 CAATCGATACAGATCTAGCGGCCGCCCGCCACCATGGCTGAAAAAGC 
               
               
                   
                 GGGGTCTACATTTTCACACCTTCTGGTTCCTATTCTTCTCCTGATTGGCT 
               
               
                   
                 GGATTGTGGGCTGCATCATAATGATTTATGTTGTCTTCTCTTAGAAGCT 
               
               
                   
                 TTGGATCCAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTG 
               
               
                   
                 GTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTT 
               
               
                   
                 AATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCT 
               
               
                   
                 CCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGT 
               
               
                   
                 TGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCC 
               
               
                   
                 CACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTC 
               
               
                   
                 GCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTG 
               
               
                   
                 CCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGG 
               
               
                   
                 TGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGC 
               
               
                   
                 CACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTC 
               
               
                   
                 AATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCT 
               
               
                   
                 CTTCCGCGTCTTCGAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCC 
               
               
                   
                 ATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCC 
               
               
                   
                 ACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTC 
               
               
                   
                 TGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCA 
               
               
                   
                 AGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGT 
               
               
                   
                 TAAGGGCAGCCAGAAGTCAGATGCTCAAGGGGCTTCATGATGTCCCCA 
               
               
                   
                 TAATTTTTGGCAGAGGGAAAAAGATCGGATCCTCAGGCGTAGTTCACC 
               
               
                   
                 CCGTCCTCGAGGCCGCCCGGGTCGACTAAAAAACCTCCCACACCTCCC 
               
               
                   
                 CCTGAACCTGAAACATAAAATGAATGCAATTGTTGTTGTTAACTTGTTT 
               
               
                   
                 ATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTC 
               
               
                   
                 ACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAAC 
               
               
                   
                 TCATCAATGTATCTTATCATGTCTGGATCCGCGCGGCCGTCAGCTGAA 
               
               
                   
                 CACCACGTAGATCATGATGATGCAGCCCACGATCCAGCCGATCAGCAG 
               
               
                   
                 CAGAATAGGGACCAGCAGGTGGCTGAAGGTAGATCCGGCCTTCTCGG 
               
               
                   
                 CCATGGTGGCGGCTAGCCTATAGTGAGTCGTATTAAGTACTCTAGCCT 
               
               
                   
                 TAAGAGCTGTAATTGAACTGGGAGTGGACACCTGTGGAGAGAAAGGC 
               
               
                   
                 AAAGTGGATGTCAGTAAGACCAATAGGTGCCTATCAGAAACGCAAGA 
               
               
                   
                 GTCTTCTCTGTCTCGACAAGCCCAGTTTCTATTGGTCTCCTTAAACCTG 
               
               
                   
                 TCTTGTAACCTTGATACTTACCTGCCCAGTGCCTCACGACCAACTTCTG 
               
               
                   
                 CAGCTTAAGTTCGAGACTGTTGTGTCAGAAGCACTGACTGCGTTAGCA 
               
               
                   
                 ATTTAACTGTGATAAACTACCGCAATAAAGCTCTAGAGCTTCGGGGAT 
               
               
                   
                 CGTCCCACGGAGCGGTGGGTGCCGGCGGCTGTCTGGGAAGGGCTCCTT 
               
               
                   
                 GGGGGGCAGAGGCTTTAAGGTCCCCCCGGCGCCCACCCCGGGGCGGG 
               
               
                   
                 CAGAGCCAGCAGGAATGTGCCCGGCGCCCAGAGAGGAATGCAACACT 
               
               
                   
                 TGTGAGCTGCTATTTTGGCAGCAGCGGCCCCGGCCCCCTCCGTGCTCC 
               
               
                   
                 CCCTTCCCCCACAGGAGCCCATATAAGCCCAAGCTATTGTGTGGCCTC 
               
               
                   
                 AGAGTTTTGCTATTTTAAACCCGTCGGACGGAGATACGTGAGTGCCCG 
               
               
                   
                 AGGGGCTGACACAAGCCAGCCAGCTGTCACCTCCCAGGGCTGGGGAC 
               
               
                   
                 GCTGATAAGGCAGCGCTTCGGACCCGACCCTCTGCCGCAGCCCCAGAT 
               
               
                   
                 GCTGTCATGTGAAAGCCCAGACTGCTTTTATCCCTGCTTGGACTTCTAA 
               
               
                   
                 TGCTGTGCTTTTCCTTCAGTTCACACCAGTTAAAAATAGAAAACTGGG 
               
               
                   
                 CACCGGCATCTCTGTCTAGAGTGGGCTTGGATTGATATGCTGAGCAGG 
               
               
                   
                 ACTGCTGATTATCTTCAGGGGCCGGGCAGTGCTGGGTCCTCCCCTCAG 
               
               
                   
                 AGCTTCTCAACCATGTTTGGGATGGTCTAGGGATGAAACTGCTGGACA 
               
               
                   
                 GCTGAGCCATGGAGACTGGGGAGAGGCCTGCCTGGCTGAGACCAAGC 
               
               
                   
                 CCTGCTGTACCATCTGCATTTGACAGTGAGGATGCCCATTGACAGGAA 
               
               
                   
                 GCAGACGTAGAGAAAAGGAGAATCAGAATGATCGACAGGCTTCAAAT 
               
               
                   
                 CCTACCTCTAACACTTAACTACGTTCCGCACGTTTGGTCTCGGGCAGGC 
               
               
                   
                 CAGTTGAATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGATA 
               
               
                   
                 AGTAGCATGGCGGGTTAATCATTAACTACAAGGAACCCCTAGTGATGG 
               
               
                   
                 AGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGC 
               
               
                   
                 GACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGA 
               
               
                   
                 GCGAGCGAGCGCGCAG (SEQ ID NO: 73) 
               
               
                   
               
               
                 pHZ62 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ33) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCGCCCTTAAGCCTTCAGATTAAAAATAACTAAGGTAAGGGCCAT 
               
               
                   
                 GTGGGTAGGGGAGGTGGTGTGAGACGGTCCTGTCTCTCCTCTATCTGC 
               
               
                   
                 CCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAAAAAAAG 
               
               
                   
                 GCCCTGGAGCCAGAGGGGCGAGGGCAGCAGACCTTTCATGGGCAAAC 
               
               
                   
                 CTCAGGGCTGCTGTCGTCATGGAGAAGACCCACCTTGCAGATGTCCTC 
               
               
                   
                 ACTGGGGCTGGCAGAGCCGGCAACCTGCCTAAGGCTGCTCAGTCCATT 
               
               
                   
                 AGGAGCCAGTAGCCTGGAAGATGTCTTTACCCCCAGCATCAGTTCAAG 
               
               
                   
                 TGGAGCAGCACATAACTCTTGCCCTCTGCCTTCCAAGATTCTGGTGCTG 
               
               
                   
                 AGACTTATGGAGTGTCTTGGAGGTTGCCTTCTGCCCCCCAACCCTGCTC 
               
               
                   
                 CCAGCTGGCCCTCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGAT 
               
               
                   
                 TCTCAAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCATATC 
               
               
                   
                 TGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGACCACATGGG 
               
               
                   
                 CTTATATGGCGTGGGGTACATGTTCCTGTAGCCTTGTCCCTGGCACCTG 
               
               
                   
                 CCAAAATAGCAGCCAACACCCCCCACCCCCACCGCCATCCCCCTGCCC 
               
               
                   
                 CACCCGTCCCCTGTCGCACATTCCTCCCTCCGCAGGGCTGGCTCACCA 
               
               
                   
                 GGCCCCAGCCCACATGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCAC 
               
               
                   
                 CCAGTCCCCGCTGAGACTGAGCAGACGCCTCCATAACTGGTAAGTACC 
               
               
                   
                 GCCTATAGACTCTATAGGCACACCCCTTTGGCTCTTATGCATGCTGACA 
               
               
                   
                 GACTAACAGACTGTTCCTTTCCTGGGTCTTTTCTGCAGGCCTGTACGGA 
               
               
                   
                 AGTGTTACTTCTGCTCTAAAAGCTGCGGAATTGTACCCGCGGCCGATC 
               
               
                   
                 CAATCGATACAGATCTAGCGGCCGCCCGCCACCATGGCTGAAAAAGC 
               
               
                   
                 GGGGTCTACATTTTCACACCTTCTGGTTCCTATTCTTCTCCTGATTGGCT 
               
               
                   
                 GGATTGTGGGCTGCATCATAATGATTTATGTTGTCTTCTCTTAGAAGCT 
               
               
                   
                 TTGGATCCAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTG 
               
               
                   
                 GTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACGCTGCTTT 
               
               
                   
                 AATGCCTTTGTATCATGCTATTGCTTCCCGTATGGCTTTCATTTTCTCCT 
               
               
                   
                 CCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGT 
               
               
                   
                 TGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCC 
               
               
                   
                 CACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTC 
               
               
                   
                 GCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTG 
               
               
                   
                 CCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGG 
               
               
                   
                 TGTTGTCGGGGAAATCATCGTCCTTTCCTTGGCTGCTCGCCTGTGTTGC 
               
               
                   
                 CACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTC 
               
               
                   
                 AATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCT 
               
               
                   
                 CTTCCGCGTCTTCGAGATCTGCCTCGACTGTGCCTTCTAGTTGCCAGCC 
               
               
                   
                 ATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCC 
               
               
                   
                 ACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTC 
               
               
                   
                 TGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCA 
               
               
                   
                 AGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGACTCGAGT 
               
               
                   
                 TAAGGGCAGCCAGAAGTCAGATGCTCAAGGGGCTTCATGATGTCCCCA 
               
               
                   
                 TAATTTTTGGCAGAGGGAAAAAGATCGGATCCTCAGGCGTAGTTCACC 
               
               
                   
                 CCGTCCTCGAGGCCGCCCGGGTCGACTAAAAAACCTCCCACACCTCCC 
               
               
                   
                 CCTGAACCTGAAACATAAAATGAATGCAATTGTTGTTGTTAAACTGGC 
               
               
                   
                 CTGCCCGAGACCAAACGTGCGGAACGTAGTTAAGTGTTAGAGGTAGG 
               
               
                   
                 ATTTGAAGCCTGTCGATCATTCTGATTCTCCTTTTCTCTACGTCTGCTTC 
               
               
                   
                 CTGTCAATGGGCATCCTCACTGTCAAATGCAGATGGTACAGCAGGGCT 
               
               
                   
                 TGGTCTCAGCCAGGCAGGCCTCTCCCCAGTCTCCATGGCTCAGCTGTC 
               
               
                   
                 CAGCAGTTTCATCCCTAGACCATCCCAAACATGGTTGAGAAGCTCTGA 
               
               
                   
                 GGGGAGGACCCAGCACTGCCCGGCCCCTGAAGATAATCAGCAGTCCT 
               
               
                   
                 GCTCAGCATATCAATCCAAGCCCACTCTAGACAGAGATGCCGGTGCCC 
               
               
                   
                 AGTTTTCTATTTTTAACTGGTGTGAACTGAAGGAAAAGCACAGCATTA 
               
               
                   
                 GAAGTCCAAGCAGGGATAAAAGCAGTCTGGGCTTTCACATGACAGCA 
               
               
                   
                 TCTGGGGCTGCGGCAGAGGGTCGGGTCCGAAGCGCTGCCTTATCAGCG 
               
               
                   
                 TCCCCAGCCCTGGGAGGTGACAGCTGGCTGGCTTGTGTCAGCCCCTCG 
               
               
                   
                 GGCACTCACGTATCTCCGTCCGACGGGTTTAAAATAGCAAAACTCTGA 
               
               
                   
                 GGCCACACAATAGCTTGGGCTTATATGGGCTCCTGTGGGGGAAGGGG 
               
               
                   
                 GAGCACGGAGGGGGCCGGGGCCGCTGCTGCCAAAATAGCAGCTCACA 
               
               
                   
                 AGTGTTGCATTCCTCTCTGGGCGCCGGGCACATTCCTGCTGGCTCTGCC 
               
               
                   
                 CGCCCCGGGGTGGGCGCCGGGGGGACCTTAAAGCCTCTGCCCCCCAA 
               
               
                   
                 GGAGCCCTTCCCAGACAGCCGCCGGCACCCACCGCTCCGTGGGACGAT 
               
               
                   
                 CCCCGAAGCTCTAGAGCTTTATTGCGGTAGTTTATCACAGTTAAATTGC 
               
               
                   
                 TAACGCAGTCAGTGCTTCTGACACAACAGTCTCGAACTTAAGCTGCAG 
               
               
                   
                 AAGTTGGTCGTGAGGCACTGGGCAGGTAAGTATCAAGGTTACAAGAC 
               
               
                   
                 AGGTTTAAGGAGACCAATAGAAACTGGGCTTGTCGAGACAGAGAAGA 
               
               
                   
                 CTCTTGCGTTTCTGATAGGCACCTATTGGTCTTACTGACATCCACTTTG 
               
               
                   
                 CCTTTCTCTCCACAGGTGTCCACTCCCAGTTCAATTACAGCTCTTAAGG 
               
               
                   
                 CTAGAGTACTTAATACGACTCACTATAGGCTAGCCGCCACCATGGCCG 
               
               
                   
                 AGAAGGCCGGATCTACCTTCAGCCACCTGCTGGTCCCTATTCTGCTGCT 
               
               
                   
                 CATCGGCTGGATCGTGGGCTGCATCATCATGATCTACGTGGTGTTCAG 
               
               
                   
                 CTGACGGCCGCGCGGATCCAGACATGATAAGATACATTGATGAGTTTG 
               
               
                   
                 GACAAACCACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAA 
               
               
                   
                 ATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCTGCAATAAAC 
               
               
                   
                 AAGTGAATTCCCGATTAGGATCTTCCTAGAGCATGGCTACGTAGATAA 
               
               
                   
                 GTAGCATGGCGGGTTAATCATTAACTACAAGGAACCCCTAGTGATGGA 
               
               
                   
                 GTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCG 
               
               
                   
                 ACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAG 
               
               
                   
                 CGAGCGAGCGCGCAG (SEQ ID NO: 74) 
               
               
                   
               
               
                 pHZ63 (human DWORF 
                 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGT 
               
               
                 version of pHZ34) 
                 CGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAG 
               
               
                   
                 AGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTTGTAGTTAATGAT 
               
               
                   
                 TAACCCGCCATGCTACTTATCTACGTAGCCATGCTCTAGGAAGATCGG 
               
               
                   
                 AATTCTCCCCAGCATGCCTGCTATTGTCTTCCCAATCCTCCCCCTTGCT 
               
               
                   
                 GTCCTGCCCCACCCCACCCCCCAGAATAGAATGACACCTACTCAGACA 
               
               
                   
                 ATGCGATGCAATTTCCTCATTTTATTAGGAAAGGACAGTGGGAGTGGC 
               
               
                   
                 ACCTTCCAGGGTCAAGGAAGGCACGGGGGAGGGGCAAACAACAGATG 
               
               
                   
                 GCTGGCAACTAGAAGGCACAGTCGAGGCAGATCTCGAAGACGCGGAA 
               
               
                   
                 GAGGCCGCAGAGCCGGCAGCAGGCCGCGGGAAGGAAGGTCCGCTGGA 
               
               
                   
                 TTGAGGGCGGAAGGGACGTAGCAGAAGGACGTCCCGCGCAGAATCCA 
               
               
                   
                 GGTGGCAACACAGGCGAGCAGCCAAGGAAAGGACGATGATTTCCCCG 
               
               
                   
                 ACAACACCACGGAATTGTCAGTGCCCAACAGCCGAGCCCCTGTCCAGC 
               
               
                   
                 AGCGGGCAAGGCAGGCGGCGATGAGTTCCGCCGTGGCAATAGGGAGG 
               
               
                   
                 GGGAAAGCGAAAGTCCCGGAAAGGAGCTGACAGGTGGTGGCAATGCC 
               
               
                   
                 CCAACCAGTGGGGGTTGCGTCAGCAAACACAGTGCACACCACGCCAC 
               
               
                   
                 GTTGCCTGACAACGGGCCACAACTCCTCATAAAGAGACAGCAACCAG 
               
               
                   
                 GATTTATACAAGGAGGAGAAAATGAAAGCCATACGGGAAGCAATAGC 
               
               
                   
                 ATGATACAAAGGCATTAAAGCAGCGTATCCACATAGCGTAAAAGGAG 
               
               
                   
                 CAACATAGTTAAGAATACCAGTCAATCTTTCACAAATTTTGTAATCCA 
               
               
                   
                 GAGGTTGATTGGATCCAAAGCTTCTAAGAGAAGACAACATAAATCATT 
               
               
                   
                 ATGATGCAGCCCACAATCCAGCCAATCAGGAGAAGAATAGGAACCAG 
               
               
                   
                 AAGGTGTGAAAATGTAGACCCCGCTTTTTCAGCCATGGTGGCGGGCGG 
               
               
                   
                 CCGCTAGATCTGTATCGATTGGATCGGCCGCGGGTACAATTCCGCAGC 
               
               
                   
                 TTTTAGAGCAGAAGTAACACTTCCGTACAGGCCTGCAGAAAAGACCCA 
               
               
                   
                 GGAAAGGAACAGTCTGTTAGTCTGTCAGCATGCATAAGAGCCAAAGG 
               
               
                   
                 GGTGTGCCTATAGAGTCTATAGGCGGTACTTACCAGTTATGGAGGCGT 
               
               
                   
                 CTGCTCAGTCTCAGCGGGGACTGGGTGAGGCAGAGGATGGAGAGGGC 
               
               
                   
                 TTTAAGCAGGCATGTGGGCTGGGGCCTGGTGAGCCAGCCCTGCGGAG 
               
               
                   
                 GGAGGAATGTGCGACAGGGGACGGGTGGGGCAGGGGGATGGCGGTG 
               
               
                   
                 GGGGTGGGGGGTGTTGGCTGCTATTTTGGCAGGTGCCAGGGACAAGG 
               
               
                   
                 CTACAGGAACATGTACCCCACGCCATATAAGCCCATGTGGTCCTCCAG 
               
               
                   
                 CTGCTCAGATAAGCTATTTAAAACCAGAGCAGATATGCAGGGAACAG 
               
               
                   
                 TCATGCAACATAAACCAGCTGTCCCTCTTGAGAATCCTGATAAAGCAG 
               
               
                   
                 AGGCCAGCAACCCAGGCCTGGGAGGGCCAGCTGGGAGCAGGGTTGGG 
               
               
                   
                 GGGCAGAAGGCAACCTCCAAGACACTCCATAAGTCTCAGCACCAGAA 
               
               
                   
                 TCTTGGAAGGCAGAGGGCAAGAGTTATGTGCTGCTCCACTTGAACTGA 
               
               
                   
                 TGCTGGGGGTAAAGACATCTTCCAGGCTACTGGCTCCTAATGGACTGA 
               
               
                   
                 GCAGCCTTAGGCAGGTTGCCGGCTCTGCCAGCCCCAGTGAGGACATCT 
               
               
                   
                 GCAAGGTGGGTCTTCTCCATGACGACAGCAGCCCTGAGGTTTGCCCAT 
               
               
                   
                 GAAAGGTCTGCTGCCCTCGCCCCTCTGGCTCCAGGGCCTTTTTAGTC 
               
               
                   
                 CTTGGGCACATTCCTCCTCCCCAAAGGGCCGATGGGCAGATAGAGGAG 
               
               
                   
                 AGACAGGACCGTCTCACACCACCTCCCCTACCCACATGGCCCTTACCT 
               
               
                   
                 TAGTTATTTTTAATCTGAAGGCTCGAGTTAAGGGCAGCCAGAAGTCAG 
               
               
                   
                 ATGCTCAAGGGGCTTCATGATGTCCCCATAATTTTTGGCAGAGGGAAA 
               
               
                   
                 AAGATCGGATCCTCAGGCGTAGTTCACCCCGTCCTCGAGGCCGCCCGG 
               
               
                   
                 GTCGACTAAAAAACCTCCCACACCTCCCCCTGAACCTGAAACATAAAA 
               
               
                   
                 TGAATGCAATTGTTGTTGTTAAACTGGCCTGCCCGAGACCAAACGTGC 
               
               
                   
                 GGAACGTAGTTAAGTGTTAGAGGTAGGATTTGAAGCCTGTCGATCATT 
               
               
                   
                 CTGATTCTCCTTTTCTCTACGTCTGCTTCCTGTCAATGGGCATCCTCACT 
               
               
                   
                 GTCAAATGCAGATGGTACAGCAGGGCTTGGTCTCAGCCAGGCAGGCCT 
               
               
                   
                 CTCCCCAGTCTCCATGGCTCAGCTGTCCAGCAGTTTCATCCCTAGACCA 
               
               
                   
                 TCCCAAACATGGTTGAGAAGCTCTGAGGGGAGGACCCAGCACTGCCC 
               
               
                   
                 GGCCCCTGAAGATAATCAGCAGTCCTGCTCAGCATATCAATCCAAGCC 
               
               
                   
                 CACTCTAGACAGAGATGCCGGTGCCCAGTTTTCTATTTTTAACTGGTGT 
               
               
                   
                 GAACTGAAGGAAAAGCACAGCATTAGAAGTCCAAGCAGGGATAAAAG 
               
               
                   
                 CAGTCTGGGCTTTCACATGACAGCATCTGGGGCTGCGGCAGAGGGTCG 
               
               
                   
                 GGTCCGAAGCGCTGCCTTATCAGCGTCCCCAGCCCTGGGAGGTGACAG 
               
               
                   
                 CTGGCTGGCTTGTGTCAGCCCCTCGGGCACTCACGTATCTCCGTCCGAC 
               
               
                   
                 GGGTTTAAAATAGCAAAACTCTGAGGCCACACAATAGCTTGGGCTTAT 
               
               
                   
                 ATGGGCTCCTGTGGGGGAAGGGGGAGCACGGAGGGGGCCGGGGCCGC 
               
               
                   
                 TGCTGCCAAAATAGCAGCTCACAAGTGTTGCATTCCTCTCTGGGCGCC 
               
               
                   
                 GGGCACATTCCTGCTGGCTCTGCCCGCCCCGGGGTGGGCGCCGGGGGG 
               
               
                   
                 ACCTTAAAGCCTCTGCCCCCCAAGGAGCCCTTCCCAGACAGCCGCCGG 
               
               
                   
                 CACCCACCGCTCCGTGGGACGATCCCCGAAGCTCTAGAGCTTTATTGC 
               
               
                   
                 GGTAGTTTATCACAGTTAAATTGCTAACGCAGTCAGTGCTTCTGACAC 
               
               
                   
                 AACAGTCTCGAACTTAAGCTGCAGAAGTTGGTCGTGAGGCACTGGGCA 
               
               
                   
                 GGTAAGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAAC 
               
               
                   
                 TGGGCTTGTCGAGACAGAGAAGACTCTTGCGTTTCTGATAGGCACCTA 
               
               
                   
                 TTGGTCTTACTGACATCCACTTTGCCTTTCTCTCCACAGGTGTCCACTC 
               
               
                   
                 CCAGTTCAATTACAGCTCTTAAGGCTAGAGTACTTAATACGACTCACT 
               
               
                   
                 ATAGGCTAGCCGCCACCATGGCCGAGAAGGCCGGATCTACCTTCAGCC 
               
               
                   
                 ACCTGCTGGTCCCTATTCTGCTGCTGATCGGCTGGATCGTGGGCTGCAT 
               
               
                   
                 CATCATGATCTACGTGGTGTTCAGCTGACGGCCGCGCGGATCCAGACA 
               
               
                   
                 TGATAAGATACATTGATGAGTTTGGACAAACCACAACTAGAATGCAGT 
               
               
                   
                 GAAAAAAATGCTTTATTTGTGAAATTTGTGATGCTATTGCTTTATTTGT 
               
               
                   
                 AACCATTATAAGCTGCAATAAACAAGTGAATTCCCGATTAGGATCTTC 
               
               
                   
                 CTAGAGCATGGCTACGTAGATAAGTAGCATGGCGGGTTAATCATTAAC 
               
               
                   
                 TACAAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCT 
               
               
                   
                 CGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGG 
               
               
                   
                 CTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG (SEQ ID NO: 
               
               
                   
                 75) 
               
               
                   
               
            
           
         
       
     
     Vectors 
     In some aspects, the disclosure provides vectors comprising the expression cassettes provided herein. The vector can be any viral vector or any non-viral vector known in the art or described herein. 
     In some embodiments, the vector is a viral vector. In some embodiments the viral vector is an adeno-associated virus vector (AAV), an adenoviral vector (AV), a lentiviral vector (LV), a retroviral vector (RV), a herpes simplex virus vector (HSV), or a poxvirus vector. 
     In some embodiments, provided herein is an AAV comprising any expression cassette described herein. In some embodiments, provided herein is an AV comprising any expression cassette described herein. In some embodiments, provided herein is an LV comprising any expression cassette described herein. In some embodiments, provided herein is an RV comprising any expression cassette described herein. In some embodiments, provided herein is an HSV comprising any expression cassette described herein. In some embodiments, provided herein is a poxvirus-based vector comprising any expression cassette described herein. 
     In some embodiments, the vector is a non-viral vector. In some embodiments, the non-viral vector is a naked DNA (e.g., a DNA plasmid). In some embodiments, the non-viral vector is a plasmid. In some embodiments, the non-viral vector is a liposome or lipid vector comprising plasmid DNA and a lipid solution. 
     For example, viral and non-viral vectors and delivery systems are described in Sung &amp; Kim 2019, Biomaterials Research 23:8; Mali, 2013, Indian Journal of Human Genetics, 19(1):3-8; Hardee et al., 2017, Genes 8:65; Bulcha et al., 2020, Signal Transduction and Targeted Therapy; Ghosh et al., 2020, Applied Biosafety: Journal of ABSA International 25(1):7-18, the disclosures of each of which are hereby incorporated by reference herein in their entireties. 
     In some embodiments, the vectors are recombinant vectors. 
     In some embodiments, the vectors described herein comprise an expression cassette comprising a polynucleotide encoding any gene product described herein. In some embodiments, the expression cassette comprises a sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NOS: 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 
     In some embodiments, the vectors described herein comprise an expression cassette comprises a polynucleotide encoding DWORF. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NOs: 20-24 and SEQ ID NOs: 45-75. 
     In some aspects of the disclosure, a vector is used to deliver the expression cassettes described herein to cardiac cells of a subject, e.g., to treat cardiomyopathy. In some embodiments, the disclosure provides a viral vector comprising an expression cassette comprising a polynucleotide encoding a gene product (such as any gene product described herein, e.g., a DWORF polypeptide) operatively linked to a promoter and a pharmaceutically acceptable carrier. In some embodiments, the disclosure provides a virion comprising a capsid and an expression cassette comprising a polynucleotide encoding a gene product (such as any gene product described herein, e.g., a DWORF polypeptide) operatively linked to a promoter and a pharmaceutically acceptable carrier. In some embodiments, the disclosure provides a plasmid comprising an expression cassette comprising a polynucleotide encoding a gene product (such as any gene product described herein, e.g., a DWORF polypeptide) operatively linked to a promoter and a pharmaceutically acceptable carrier. 
     In some embodiments, the viral vectors described herein are replication incompetent, in that it cannot independently further replicate and package its genome. For example, when a cardiac cell is targeted with a virion, the transgene is expressed in the targeted cardiac cell, however, due to the fact that the targeted cardiac cell lacks packaging and accessory function genes, the virion is not able to replicate. In some embodiments, the viral vectors described herein are replication-competent. 
     In some embodiments, the vectors described herein are capable of being delivered to both dividing and non-dividing cells. In some embodiments, the vectors described herein are capable of being delivered to non-dividing cells. In some embodiments, the vectors described herein are capable of being delivered to dividing cells. 
     In some embodiments, the vectors comprising the expression cassettes described herein lead to cardiac cell-specific expression of a transgene. In some embodiments, the vectors comprising the expression cassettes described herein lead to cardiomyocyte-specific expression of a transgene. In some embodiments, the vectors comprising the expression cassettes described herein allow high expression of a transgene in a cardiac cell (e.g., a cardiornyocyte) and low or no expression in other cells (e.g., low or no expression in liver cells, low or no expression in muscle cells except for muscle cells of the heart, low or no expression in cardiac fibroblasts). In some embodiments, the vectors comprising the expression cassettes described herein allow high expression of a transgene in heart tissue of a subject (e.g., in human heart). In some embodiments, the vectors comprising the expression cassettes described herein allow no or low expression of a transgene in tissues of a subject other than the heart (e.g., in liver or in muscles except those of the heart). “High” and “low” can be relative to each other, for example, the expression of a transgene in cardiac cells (e.g, cardiomyocytes) and/or heart tissue can be at least 2 fold, 5 fold, 10 fold, 15 fold, 20 fold, 50 fold, 100 fold, 150 fold, or 200 fold higher than its expression in other cells and tissues (e.g., liver, muscle except for the heart). 
     Recombiant AAV Virions 
     In some aspects, the disclosure provides recombinant AAV (rAAV) virions comprising the expression cassettes provided herein. In some embodiments, the rAAV virion comprises a capsid protein and an expression cassette. In some embodiments, the expression cassette comprises a polynucleotide encoding any gene product described herein. 
     In some embodiments, the expression cassette comprises a polynucleotide encoding DWORF. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NOs: 20-24 and SEQ ID NOs: 45-63. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 61. In some embodiments, the expression cassette comprises SEQ ID NO: 61. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 62. In some embodiments, the expression cassette comprises SEQ ID NO: 62. In some embodiments, the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 63. In some embodiments, the expression cassette comprises SEQ ID NO: 63. 
     In some aspects of the disclosure, an rAAV virion is used to deliver the expression cassettes described herein to cardiac cells of a subject, e.g., to treat cardiomyopathy. Accordingly, the disclosure provides an rAAV virion, the rAAV virion comprising an AAV capsid and an expression cassette comprising a polynucleotide encoding a DWORF polypeptide operatively linked to a promoter and a pharmaceutically acceptable carrier. 
     The rAAV virions of the disclosure comprise a capsid protein. Capsid proteins are structural proteins that make up the assembled icosahedral packaging of the rAAV virion that contains the expression cassette. Capsid proteins are classified by the serotype. Wild type capsid serotypes in rAAV virions can be, for example, AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, or AAV12 (Naso et al.  BioDrugs  31:317-334 (2017)). Engineered capsid types include chimeric capsids and mosaic capsids (Choi et al.  Curr Gene Ther.  5: 299-310 (2005)). Capsids are selected for rAAV virions based on their ability to transduce specific tissue or cell types (Liu et al.  Curr Pharm Des.  21:3248-56 (2015)). 
     Any capsid protein that can facilitate rAAV virion transduction into cardiac cells for delivery of a transgene, as described herein, can be used. Capsid proteins used in rAAV virions for transgene delivery to cardiac cells that result in high expression can be, for example, AAV4, AAV6, AAV7, AAV8, and AAV9 (Zincarelli et al.  Mol. Ther.  16:P1073-1080 (2008)). Artificial capsids, such as chimeric capsids generated through combinatorial libraries, can also be used for transgene delivery to cardiac cells that results in high expression (see U.S. 63/012,703, the contents of which are herein incorporated by reference). Other capsid proteins with various features can also be used in the rAAV virions of the disclosure. AAV vectors and capsids are provided in U.S. Pat. Pub. Nos. U.S. Pat. Nos. 10,011,640B2; 7,892,809B2, 8,632,764B2, 8,889,641B2, 9,475,845B2, 10,889,833B2, 10,480,011B2, and 10,894,949B2, the contents of which are herein incorporated by reference; and Int&#39;l Pat. Pub. Nos. WO2020198737A1, WO2019028306A2, WO2016054554A1, WO2018152333A1, WO2017106236A1, WO2008124724A1, WO2017212019A1, WO2020117898A1, WO2017192750A1, WO2020191300A1, and WO2017100671A 1, the contents of which are herein incorporated by reference. 
     In some embodiments, the rAAV virions of the disclosure comprise an engineered capsid protein. Engineered capsid proteins can be derived from a parental, e.g., wild type, capsid and include, for example, variant polypeptide sequence with respect to a parental capsid sequence at one or more sites. For example, variant sites of the parental capsid can occur at the VR-IV site, VR-V site, VR-VII site and/or VR-VIII site (see, e.g., Büning and Srivastava.  Mol Ther Methods Clin Dev.  12:248-265 (2019)). 
     In some embodiments, the capsid protein is an AAV5/AAV9 chimeric capsid protein. In some embodiments, the chimeric capsid protein comprises at least 1, 2, 3, 4, 5 or more polypeptide segments that are derived from AAV5 capsid protein (SEQ ID NO. 144). In some embodiments, the chimeric capsid protein comprises at least 1, 2, 3, 4, 5 or more polypeptide segments that are derived from AAV9 capsid protein (SEQ ID NO: 143). In some embodiments, at least one polypeptide segment is derived from the AAV5 capsid protein and at least one polypeptide segment is derived from the AAV9 capsid protein. 
     In some embodiments, the capsid protein is a combinatory capsid proteins. As used herein, “combinatory capsid protein” refers to a AAV5/AAV9 chimeric capsid protein, which further comprises amino acid variations with respect to the chimeric parental sequence at one or more sites. In some embodiments, the one or more sites of the chimeric parental sequence are selected from those equivalent to the VR-IV site, the VR-V site, the VR-VII site and the VR-VIII site of the AAV9 capsid protein. 
     In some embodiments, the rAAV virions comprise an engineered capsid protein selected from Table 7. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Engineered Capsid  
               
               
                 Proteins 
               
            
           
           
               
               
               
            
               
                   
                 Engineered 
                 SEQ 
               
               
                   
                 Capsid 
                 ID NO: 
               
               
                   
                   
               
               
                   
                 CR9-01 
                 145 
               
               
                   
                 CR9-07 
                 146 
               
               
                   
                 CR9-08 
                 147 
               
               
                   
                 CR9-09 
                 148 
               
               
                   
                 CR9-10 
                 149 
               
               
                   
                 CR9-11 
                 150 
               
               
                   
                 CR9-13 
                 151 
               
               
                   
                 CR9-14 
                 152 
               
               
                   
                 CR9-15 
                 153 
               
               
                   
                 CR9-16 
                 154 
               
               
                   
                 CR9-17 
                 155 
               
               
                   
                 CR9-20 
                 156 
               
               
                   
                 CR9-21 
                 157 
               
               
                   
                 CR9-22 
                 158 
               
               
                   
                 ZC23 
                 159 
               
               
                   
                 ZC24 
                 160 
               
               
                   
                 ZC25 
                 161 
               
               
                   
                 ZC26 
                 162 
               
               
                   
                 ZC27 
                 163 
               
               
                   
                 ZC28 
                 164 
               
               
                   
                 ZC29 
                 165 
               
               
                   
                 ZC30 
                 166 
               
               
                   
                 ZC31 
                 167 
               
               
                   
                 ZC32 
                 168 
               
               
                   
                 ZC33 
                 169 
               
               
                   
                 ZC34 
                 170 
               
               
                   
                 ZC35 
                 171 
               
               
                   
                 ZC40 
                 172 
               
               
                   
                 ZC41 
                 173 
               
               
                   
                 ZC42 
                 174 
               
               
                   
                 ZC43 
                 175 
               
               
                   
                 ZC44 
                 176 
               
               
                   
                 ZC45 
                 177 
               
               
                   
                 ZC46 
                 178 
               
               
                   
                 ZC47 
                 179 
               
               
                   
                 ZC48 
                 180 
               
               
                   
                 ZC49 
                 181 
               
               
                   
                 ZC50 
                 182 
               
               
                   
                 TN47-07 
                 183 
               
               
                   
                 TN47-10 
                 184 
               
               
                   
                 TN47-13 
                 185 
               
               
                   
                 TN47-14 
                 186 
               
               
                   
                 TN47-17 
                 187 
               
               
                   
                 TN47-22 
                 188 
               
               
                   
                 TN40-07 
                 189 
               
               
                   
                 TN40-10 
                 190 
               
               
                   
                 TN40-13 
                 191 
               
               
                   
                 TN40-14 
                 192 
               
               
                   
                 TN40-17 
                 193 
               
               
                   
                 TN40-22 
                 194 
               
               
                   
                 TN44-07 
                 195 
               
               
                   
                 TN44-10 
                 196 
               
               
                   
                 TN44-13 
                 197 
               
               
                   
                 TN44-14 
                 198 
               
               
                   
                 TN44-17 
                 199 
               
               
                   
                 TN44-22 
                 200 
               
               
                   
                   
               
            
           
         
       
     
     In some embodiments, the rAAV is replication defective, in that the rAAV virion cannot independently further replicate and package its genome. For example, when a cardiac cell is targeted with rAAV virions, the transgene is expressed in the targeted cardiac cell, however, due to the fact that the targeted cardiac cell lacks AAV rep and cap genes and accessory function genes, the rAAV is not able to replicate. 
     In some embodiments, rAAV virions of the present disclosure encapsulating the expression cassettes as described herein, can be produced using helper-free production, rAAVs are replication-deficient viruses and normally require components from a live helper virus, such as adenovirus, in a host cell for packaging of infectious rAAV virions. rAAV helper-free production systems allow the production of infectious rAAV virions without the use of a live helper virus. In the helper-free system, a host packaging cell line is co-transfected with three plasmids. A first plasmid may contain adenovirus gene products (e.g., E2A, E4, and VA RNA genes) needed for the packaging of rAAV virions. A second plasmid may contain required AAV genes (e.g., REP and CAP genes). A third plasmid contains the polynucleotide sequence encoding the transgene of interest and a promoter flanked by ITRs. A host packaging cell line can be, for example, AAV-293 host cells. Suitable host cells contain additional components required for packaging infectious rAAV virions that are not supplied by the plasmids. In some embodiments, the CAP genes can encode, for example, AAV capsid proteins as described herein. 
     In some embodiments, the CAP genes can encode, for example, AAV capsid proteins as described herein. In some embodiments, the promoter is a promoter sequence as described herein. In some embodiments, the promoter sequence is a cTnT promoter sequence. In some embodiments, the polypeptide of interest is a DWORF polypeptide. 
     The expression cassettes, enhancers and/or promoters described herein with respect to AAV virions need not be limited to their use in AAV virions and can be incorporated in essentially any other construct where expression of a polynucleotide encoding a gene product is desired. 
     rAAV virions can deliver transgenes to cells in a subject that are, in turn, expressed in the cell. A transgene delivered by an rAAV virion may be incorporated into the genome of the targeted cell, allowing for potential long-term expression of the transgene product. Compared to other viral transgene delivery systems, such as adenoviruses, rAAV virions have the advantage of low immunogenicity. rAAV virions can be used to transduce and deliver transgenes to many cells types, including eye, blood, liver, heart, joint tissue, muscle, brain kidney or lung cells (U.S. Pat. Nos. 10,308,957; 9,803,218). rAAV virions can contain genomes up to about 5.2 kilobases (kb), limiting the size of the polynucleotide that can be integrated into the host cell to about 4.4 kb (Choi et al.  Mol Brain.  7:1 (2014)). 
     Methods of Use 
     Methods of Increasing Polypeptide Expression 
     The disclosure provides methods of increasing polypeptide expression in a cell comprising contacting the cell with any vector or virion (e.g., rAAV virion) described herein. In some embodiments, the cell is a cardiac cell. In some embodiments, the cell is a cardiomyocyte. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. In some embodiments, the polypeptide is any polypeptide for use in treating or preventing a heart disease. In some embodiments, the polypeptide is any polypeptide described herein. In some embodiments, the polypeptide is encoded by any transgene described herein. 
     The disclosure provides methods of increasing polypeptide expression in a tissue comprising contacting the tissue with any vector or virion (e.g., rAAV virion) described herein. In some embodiments, the tissue is cardiac tissue. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. 
     The disclosure provides methods of increasing polypeptide expression in an organ comprising contacting the organ with any vector or virion (e.g., rAAV virion) described herein. In some embodiments, the organ is a heart. In some embodiments, the heart is diseased or at risk of disease. In some embodiments, the heart has borderline or reduced ejection fraction. In some embodiments, the heart has a normal ejection fraction. In some embodiments, the heart comprises a genetic mutation associated with a heart disease. In some embodiments, the genetic mutation is a PLN mutation. In some embodiments, the heart has low or undetectable polypeptide expression compared to a healthy heart. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. 
     The disclosure provides methods of increasing polypeptide expression in a subject comprising administering to the subject any vector or virion (e.g., rAAV virion) described herein. In some embodiments the subject is an animal. An animal can be, without limitation, a mouse, rat, dog, or non-human primate. In some embodiments, the subject is a human. In some embodiments, the increased polypeptide expression is in the heart of the subject. In some embodiments, the subject has a heart disease or is at risk of a heart disease. In some embodiments, the subject has borderline or reduced ejection fraction. In some embodiments, the subject has a normal ejection fraction. In some embodiments, the subject has a genetic mutation associated with a heart disease. In some embodiments, the genetic mutation is a PLN mutation. In some embodiments, the subject has low or undetectable level of DWORF expression compared to a healthy subject. 
     In some embodiments, the polypeptide is expressed in a cell, tissue, organ, or subject at a desired level of expression. A “desired level of expression” can be selected such that the level of expression is relative to the polypeptide expression in a healthy or diseased cell, tissue, organ, or subject. For example, an increased level in polypeptide expression relative to a diseased cardiac cell, cardiac tissue, heart, or subject with a heart disease or disorder can be a desired level of expression. The desired level of expression can be expressed relative to the difference in expression achieved between different vector or virions (e.g., rAAV virions) containing different expression cassettes. For example, a vector or virion (e.g., rAAV virion) comprising an expression cassette comprising a promoter and an enhancer may achieve a desired level of expression compared to a vector or virion (e.g., rAAV virion) comprising only a promoter. 
     The polypeptide expression level achieved by any vector or virion (e.g., rAAV virion) comprising an expression cassette can be described as a “fold” change (i.e., increase or decrease) compared to basal polypeptide expression. The polypeptide expression level achieved by a vector or virion (e.g., rAAV virion) comprising an expression cassette can be described as a “fold change” compared to polypeptide expression achieved by an expression cassette comprising a single promoter, no enhancers, and a sequence encoding the polypeptide. Fold change is a relative quantity, such that the levels of expression between the expression level achieved by an expression cassette and reference expression level are expressed as a ratio. It is understood that when describing fold change of polypeptide expression, “about” refers to ±0.5-fold. Polypeptide expression levels can be categorized as “low expression”, “medium expression”, or “high expression.” “Low expression” is meant to include expression levels between about 1.5-fold and 20-fold increase in polypeptide expression. “Medium expression” is meant to include expression levels between about 20-fold increase and about 60-fold increase in polypeptide expression. “High expression” is meant to include expression levels between about 60-fold and 140-fold increase in polypeptide expression. 
     In some embodiments, the polypeptide expression level is between about a 1.5-fold and 150-fold increase. In some embodiments, the polypeptide expression level is increased at least about 1.5-fold, about 3.5-fold, about 5.5-fold, about 7.5-fold, about 9.5-fold, about 11.5-fold, about 13.5-fold, about 15.5-fold, about 17.5-fold, about 19.5-fold, about 21.5-fold, about 23.5-fold, about 25.5-fold, about 27,5-fold, about 29.5-fold, about 31.5-fold, about 33.5-fold, about 35.5-fold, about 37.5-fold, about 39.5-fold, about 41.5-fold, about 43.5-fold, about 45.5-fold, about 47.5-fold, about 49.5-fold, about 51.5-fold, about 53,5-fold, about 55.5-fold, about 57.5-fold, about 59.5-fold, about 61.5-fold, about 63.5-fold, about 65.5-fold, about 67.5-fold, about 69.5-fold, about 71.5-fold, about 73.5-fold, about 75.5-fold, about 77.5-fold, about 79.5-fold, about 81.5-fold, about 83.5-fold, about 85.5-fold, about 87.5-fold, about 89.5-fold, about 91.5-fold, about 93.5-fold, about 95.5-fold, about 97.5-fold, about 99.5-fold, about 101.5-fold, about 103.5-fold, about 105.5-fold, about 107.5-fold, about 109.5-fold, about 111.5-fold, about 113.5-fold, about 115.5-fold, about 117.5-fold, about 119.5-fold, about 121.5-fold, about 123.5-fold, about 125.5-fold, about 127.5-fold, about 129.5-fold, about 131.5-fold, about 133.5-fold, about 135.5-fold, about 137.5-fold, about 139.5-fold, about 141.5-fold, about 143.5-fold, about 145.5-fold, about 147.5-fold, or about 149.5-fold. 
     In some embodiments, the polypeptide expression level is increased at least or more than about 5-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 10-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 15-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 25-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 35-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 50-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 60-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 75-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 85-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 100-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 110-fold. In some embodiments, the polypeptide expression level is increased at least or more than about 125-fold. 
     In some embodiments, the fold increase is relative to an expression cassette comprising a single promoter, no enhancers, and a sequence encoding the polypeptide. In some embodiments, the fold increase is relative to a healthy cell, tissue, organ, or subject. In some embodiments, the fold increase is relative to a diseased cell, tissue, organ, or subject. 
     Methods of Increasing DWORF Expression 
     The disclosure provides methods of increasing DWORF expression in a cell comprising contacting the cell with the rAAV virions described herein. In some embodiments, the cell is a cardiac cell. In some embodiments, the cell is a cardiomyocyte. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. 
     The disclosure provides methods of increasing DWORF expression in a tissue comprising contacting the tissue with the rAAV virions described herein. In some embodiments, the tissue is cardiac tissue. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. 
     The disclosure provides methods of increasing DWORF expression in an organ comprising contacting the organ with the rAAV virions described herein. In some embodiments, the organ is a heart. In some embodiments, the heart is diseased or at risk of disease. In some embodiments, the heart has borderline or reduced ejection fraction. In some embodiments, the heart has a normal ejection fraction. In some embodiments, the heart comprises a genetic mutation associated with a heart disease. In some embodiments, the genetic mutation is a PLN mutation. In some embodiments, the heart has low or undetectable DWORF expression compared to a healthy heart. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. 
     The disclosure provides methods of increasing DWORF expression in a subject comprising administering to the subject the rAAV virions described herein. In some embodiments the subject is an animal. An animal can be, without limitation, a mouse, rat, dog, or non-human primate. In some embodiments, the subject is a human. In some embodiments, the increased DWORF expression is in the heart of the subject. In some embodiments, the subject has a heart disease or is at risk of a heart disease. In some embodiments, the subject has borderline or reduced ejection fraction. In some embodiments, the subject has a normal ejection fraction. In some embodiments, the subject has a genetic mutation associated with a heart disease. In some embodiments, the genetic mutation is a PLN mutation. In some embodiments, the subject has low or undetectable level of DWORF expression compared to a healthy subject. 
     In some embodiments, DWORF is expressed in a cell, tissue, organ, or subject at a desired level of expression. A “desired level of expression” can be selected such that the level of expression is relative to DWORF expression in a healthy or diseased cell, tissue, organ, or subject. For example, an increased level in DWORF expression relative to a diseased cardiac cell, cardiac tissue, heart, or subject with a heart disease or disorder can be a desired level of expression. The desired level of expression can be expressed relative to the difference in expression achieved between different rAAV virions containing different expression cassettes. For example, an rAAV virion comprising an expression cassette comprising a promoter and an enhancer may achieve a desired level of expression compared to an rAAV virion comprising only a promoter. 
     The DWORF expression level achieved by an rAAV virion comprising an expression cassette can be described as a “fold” change (i.e., increase or decrease) compared to basal DWORF expression. The DWORF expression level achieved by an rAAV virion comprising an expression cassette can be described as a “fold change” compared to DWORF expression achieved by an expression cassette comprising a single promoter, no enhancers, and a sequence encoding DWORF. Fold change is a relative quantity, such that the levels of expression between the expression level achieved by an expression cassette and reference expression level are expressed as a ratio. It is understood that when describing fold change of DWORF expression, “about” refers to ±0.5-fold. DWORF expression levels can be categorized as “low expression”, “medium expression”, or “high expression.” “Low expression” is meant to include expression levels between about 1.5-fold and 20-fold increase in DWORF expression. “Medium expression” is meant to include expression levels between about 20-fold increase and about 60-fold increase in DWORF expression. “High expression” is meant to include expression levels between about 60-fold and 140-fold increase in DWORF expression. 
     In some embodiments, the DWORF expression level is between about a 1.5-fold and 150-fold increase. In some embodiments, the DWORF expression level is increased about 1.5-fold, about 3.5-fold, about 5.5-fold, about 7.5-fold, about 9.5-fold, about 11.5-fold, about 13.5-fold, about 15.5-fold, about 17.5-fold, about 19.5-fold, about 21.5-fold, about 23.5-fold, about 25.5-fold, about 27.5-fold, about 29.5-fold, about 31.5-fold, about 33.5-fold, about 35.5-fold, about 37.5-fold, about 39.5-fold, about 41.5-fold, about 43.5-fold, about 45.5-fold, about 47.5-fold, about 49.5-fold, about 51.5-fold, about 53.5-fold, about 55.5-fold, about 57.5-fold, about 59.5-fold, about 61.5-fold, about 63.5-fold, about 65.5-fold, about 67.5-fold, about 69.5-fold, about 71.5-fold, about 73.5-fold, about 75.5-fold, about 77.5-fold, about 79.5-fold, about 81.5-fold, about 83.5-fold, about 85.5-fold, about 87.5-fold, about 89.5-fold, about 91.5-fold, about 93.5-fold, about 95.5-fold, about 97.5-fold, about 99.5-fold, about 101.5-fold, about 103.5-fold, about 105.5-fold, about 107.5-fold, about 109.5-fold, about 111.5-fold, about 113.5-fold, about 115.5-fold, about 117.5-fold, about 119.5-fold, about 121.5-fold, about 123.5-fold, about 125.5-fold, about 127.5-fold, about 129.5-fold, about 131.5-fold, about 133.5-fold, about 135.5-fold, about 137.5-fold, about 139.5-fold, about 141.5-fold, about 143.5-fold, about 145.5-fold, about 147.5-fold, or about 149.5-fold. 
     In some embodiments, the DWORF expression level is increased at least or more than about 5-fold. In some embodiments, the DWORF expression level is increased at least or more than about 10-fold. In some embodiments, the DWORF expression level is increased at least or more than about 15-fold. In some embodiments, the DWORF expression level is increased at least or more than about 25-fold. In some embodiments, the DWORF expression level is increased at least or more than about 35-fold. In some embodiments, the DWORF expression level is increased at least or more than about 50-fold. In some embodiments, the DWORF expression level is increased at least or more than about 60-fold. In some embodiments, the DWORF expression level is increased at least or more than about 75-fold. In some embodiments, the DWORF expression level is increased at least or more than about 85-fold. In some embodiments, the DWORF expression level is increased at least or more than about 100-fold. In some embodiments, the DWORF expression level is increased at least or more than about 110-fold. In some embodiments, the DWORF expression level is increased at least or more than about 125-fold. 
     In some embodiments, the fold increase is relative to an expression cassette comprising a single promoter, no enhancers, and a sequence encoding DWORF. In some embodiments, the fold increase is relative to a healthy cell, tissue, organ, or subject. In some embodiments, the fold increase is relative to a diseased cell, tissue, organ, or subject. 
     Methods of Treatment 
     In an aspect, any vector comprising an expression cassette described herein may be used for treating disease, such as heart disease. 
     In an aspect, rAAV virions comprising an expression cassette described herein may be used for treating disease (Wang et al.  Nat Rev Drug Discov.  18:358-378 (2019)). For treatment, rAAV virions have been used to deliver transgenes encoding polypeptides such as microdystrophin (Chamberlain et al.  Mol Ther.  25:1125-1131 (2017)), glial cell line-derived neurotrophic factor (McFarthing et al.  J Parkinsons Dis.  9:251-264 (2019)), and Factor IX (Nathwani et al.  N Engl J Med.  371:1994-2004 (2014)). 
     A variety of strategies for treating heart failure using rAAV-based delivery of a transgene have been pursued in vivo. In a pig model of heart failure, β-adrenergic receptor, a regulator of contractility, has been targeted by delivery of a small polypeptide, βARKct that indirectly prevents disruption of β-adrenergic receptor signaling (Raake et al.  Fur Heart J.  34:1437-47 (2013)). In a canine model, cardiomyocyte viability was enhanced by rAAV-based delivery of a vascular endothelial growth factor (VEGF) isoform. In human clinical trials, rAAV-based delivery of an isoform of the SERCA calcium pump, SERCA2a, to the heart was tested as a treatment for heart failure. SERCA, or sarco/endoplasmic reticulum Ca 2+ -ATPase, or SR Ca 2+ -ATPase, is a calcium ATPase-type P-ATPase. SERCA resides in the sarcoplasmic reticulum (SR) within muscle cells, It is a Ca 2+  ATPase that transfers Ca 2+  from the cytosol of the cell to the lumen of the SR at the expense of ATP hydrolysis during muscle relaxation. SERCA activity is necessary for proper contractile function of the heart. However, direct replacement of SERCA activity by rAAV-based delivery of the SERCA2a isoform failed to show a significant effect in clinical trials (Bass-Stringer et al.  Heart, Lung and Circulation.  27:1285-1300 (2018)). Enhancing SERCA activity using alternative strategies is desired for treating diseases of the heart, e.g., heart failure and cardiomyopathy. 
     There are three major domains on the cytoplasmic face of SERCA: the phosphorylation and nucleotide-binding, domains, which form the catalytic site, and the actuator domain, which is involved in the transmission of major conformational changes. The rate at which SERCA moves Ca 2+  across the SR membrane can be controlled by the regulatory protein phospholamban (PLN). SERCA is normally inhibited by PLN, with which it is closely associated. Increased β-adrenergic stimulation reduces the association between SERCA and PLN by the phosphorylation of PLN by PKA. When PLN is associated with SERCA, the rate of Ca 2+  movement is reduced; upon dissociation of PLN, Ca 2+  movement increases. 
     An alternative strategy to enhancing SERCA activity by delivering a SERCA2a isoform is to enhance activity of natively expressed SERCA by displacing PLN. Contacting SERCA with the DWORF polypeptide, described in detail above, can displace PLN and enhance SERCA activity. 
     In some embodiments, the disclosure provides a method of treating a heart disease or disorder in a subject in need thereof, the method comprising administering an effective amount of a vector comprising an expression cassette comprising a polynucleotide encoding a therapeutic polypeptide operatively linked to a promoter, wherein the therapeutic polypeptide can be any polypeptide useful for treating heart disease. As described herein, the vector can be any viral or non-viral vector. 
     In some embodiments, the disclosure provides a method of treating a heart disease or disorder in a subject in need thereof, the method comprising administering an effective amount of a recombinant adeno-associated virus (rAAV) virion, the rAAV virion comprising an AAV capsid and an expression cassette comprising a polynucleotide encoding a DWORF polypeptide operatively linked to a promoter. 
     In a method of treating a subject as described herein, “treating” or “treatment of a condition or subject in need thereof” refers to (1) taking steps to obtain beneficial or desired results, including clinical results such as the reduction of symptoms; (2) inhibiting the disease, for example, arresting or reducing the development of the disease or its clinical symptoms; (3) relieving the disease, for example, causing regression of the disease or its clinical symptoms; or (4) delaying the disease. For purposes of the methods described herein, beneficial or desired clinical results include, but are not limited to, reduction of symptoms associated with heart failure, cardiomyopathy, dilated cardiomyopathy, myocardial infarction, acute myocardial infarction, and chronic myocardial infarction. 
     In other aspects, the disclosure provides a method of preventing a heart disease or disorder in a subject in need thereof, the method comprising administering an effective amount of a vector comprising an expression cassette comprising a polynucleotide encoding a therapeutic polypeptide operatively linked to a promoter, wherein the therapeutic polypeptide can be any polypeptide useful for preventing heart disease. As described herein, the vector can be any viral or non-viral vector. In some embodiments, prevention of a disease causes the clinical symptoms of the disease not to develop in a patient that may be predisposed to the disease, but does not yet experience or display symptoms of the disease. 
     Subjects in need of treatment using the compositions and methods of the present disclosure include, but are not limited to, a subject suffering from or being at risk of heart failure. A subject “suffering from” heart failure is considered to have symptoms associated with or a confirmed diagnosis of any of the heart diseases described herein. A subject “at risk of” heart failure is considered to have one or more risk factors associated with any of the heart diseases described herein. 
     In some embodiments, the methods described herein are useful to treat heart disease or disorder with reduced ejection fraction (HFrEF). In some embodiments, the methods described herein are useful to treat heart disease or disorder with preserved ejection fraction (HFpEF). 
     In some embodiments, the methods described herein are useful to treat cardiomyopathy. In some embodiments, a method described herein is useful to treat dilated cardiomyopathy. In some embodiments, the subject suffers from or is at risk for cardiomyopathy. In some embodiments, the cardiomyopathy is dilated cardiomyopathy (DCM). In some embodiments, the DCM is genetic DCM (e.g., DCM associated with a PLN mutation in a subject to be treated). In some embodiments, the methods described herein are useful to treat PLN mutation-associated cardiomyopathy. In some embodiments, the DCM is non-genetic DCM. In some embodiments, subject suffers from or is at risk for myocardial infarction. In some embodiments, the myocardial infarction is chronic myocardial infarction. In some embodiments, the myocardial infarction is acute myocardial infarction. 
     Cardiomyopathy phenotypes can manifest in a subject through a multitude of molecular mechanisms. Transgenic animals have been developed to investigate the molecular pathophysiology of specific mechanisms and the efficacy of potential therapeutic and prevention strategies for cardiomyopathy phenotypes (Law et al.  J Clin Med.  9:520 (2020)). These animal models can be used to evaluate aspects of the rAAV viral genomes, rAAV virions, and compositions thereof described herein. The MLP −/−  transgenic mouse model, for example, recapitulates the phenotype of dilated cardiomyopathy by knocking out the muscle LIM protein, a positive regulator of myogenic differentiation associated with the actin-based cytoskeleton. The absence of LIM protein results in a disruption of cytoskeletal architecture and decreased Ca 2+  cycling (Minamisawa et al.  Cell.  99:313-22 (1999)). Artificial replacement with a phosphomimetic PLN transgene delivered by rAAV reduced DCM symptoms in the animals, including improved ejection fraction (Iwanaga Y et al.  J Clin Invest,  113:727-736 (2004). While the MLP −/−  model recapitulates DCM phenotype in a general way, other transgenic mouse models of DCM are more appropriate for specific DCM phenotypes, such as those driven by a mutation to the PLN gene. For example, a transgenic mouse model to recapitulate the clinically observed PLN-R14Del mutation has been developed (Haghighi et al.  Proc. Natl. Acad. Sci. U.S.A  103:1388-1393 (2006)). It is expected that mouse models with different transgenic modifications to induce a DCM phenotype are not interchangeable for the purpose of evaluating the efficacy of a given therapeutic or prevention strategy, and that each model provides different information about the translation of a therapy. 
     In some embodiments, the subject in need of treatment has an inherited risk allele (i.e., mutation) for a heart disease or disorder. A risk allele can be, for example, a mutation to the PLN gene. Mutations to the PLN gene can cause a dysfunctional inhibitory effect on SERCA activity. Clinically observable mutations in the PLN gene and protein include a mutation in the PLN promoter, a truncation resulting in a PLN L39stop  mutant, aberrant R9C, R9L, and R9H mutations, PLN gene duplications, and deletion of arginine 14 (R14del) in the regulatory domain of PLN. Each of these mutations have been directly linked to dilated cardiomyopathy, hypertrophic cardiomyopathy, or arrhythmic right ventricular cardiomyopathy (Table 8.) (Landstrom et al.  Am Heart J.  161:165-171 (2011), Lee et al.  Cardiol Young.  24:953-954 (2014); Haghighi et al.  J. Clin. Invest.  111:869-876 (2003); Schmitt et al.  Science  299:1410-1413 (2003); Haghighi et al.  Proc. Natl. Acad. Sci. U.S.A  103:1388-1393 (2006); Medeiros A et al. Am. Heart J. 162:1088-1095 (2011)). 
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 PLN mutations and associated heart diseases 
               
            
           
           
               
               
            
               
                 PLN Mutation 
                 Associated Heart Disease 
               
               
                   
               
               
                 PLN promoter  
                 Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy 
               
               
                 mutation 
                   
               
               
                 PLN L39stop   
                 Dilated Cardiomyopathy; Hypertrophic Cardiomyopathy 
               
               
                 R9C 
                 Dilated Cardiomyopathy 
               
               
                 R9L 
                 Dilated Cardiomyopathy 
               
               
                 R9H 
                 Dilated Cardiomyopathy 
               
               
                 PLN gene  
                 Dilated Cardiomyopathy 
               
               
                 duplication 
                   
               
               
                 R14del 
                 Dilated Cardiomyopathy; Arrhythmic Right Ventricular Cardiomyopathy 
               
               
                   
               
            
           
         
       
     
     The various mutations in PLN have different mechanisms of inducing a cardiomyopathy phenotype. For example, the R9C mutation indirectly blocks the phosphorylation of PLN by PKA and prevents the formation of monomeric PLN that can bind to SERCA. In some embodiments, the subject in need of treatment has a PLN promoter mutation. In some embodiments, the subject in need of treatment has a PLN L39stpo  mutation. In some embodiments, the subject in need of treatment has a R9C mutation. In some embodiments, the subject in need of treatment has a R9L mutation. In some embodiments, the subject in need of treatment has a R9H mutation. In some embodiments, the subject in need of treatment has a PLN gene duplication. In some embodiments, the subject in need of treatment has a R14del mutation. 
     Mutations can be detected by many types of genetic analysis known in the art. Genetic analysis can be, for example, direct sequencing, fluorescent in sun hybridization assays, polymerase chain reaction-based assays, nucleotide microarray assays, or any other technique known in the art to determine the sequence characteristics of polynucleotides sampled from a subject. For example, DNA was isolated from the peripheral blood samples patients diagnosed with either dilated cardiomyopathy (DCM) or arrhythmic right ventricular cardiomyopathy (ARVC). The coding region of the PLN gene in the isolated DNA was sequenced using a BigDye Terminator DNA sequencing kit (version 2.0) on a 3730 Genetic Analyzer (Applied Biosystems, Foster City, Calif., USA). Patients diagnosed with either DCM or ARVC both carried the PLN R14del mutation (van der Zwaag et al.  Eur J Heart Fail.  14:1199-1207 (2012)). 
     Methods of Reducing, Improving, and Preventing Symptoms 
     In some embodiments, the disclosure provides a method of reducing one or more symptoms of a heart disease or disorder in a subject comprising administration of any vector comprising an expression cassette described herein. In some embodiments, the symptoms are reduced compared to the symptoms of the heart disease or disorder prior to administration of the vector comprising an expression cassette described herein to the subject. In some embodiments, the disclosure provides a method of reducing one or more symptoms of a heart disease or disorder in a subject comprising administration of an rAAV virion described herein. In some embodiments, the symptoms are reduced compared to the symptoms of the heart disease or disorder prior to administration of the rAAV virion to the subject. In some embodiments, the heart disease or disorder is heart failure. In some embodiments, the heart disease or disorder is cardiomyopathy. In some embodiments, the heart disease or disorder is dilated cardiomyopathy. In some embodiments, the heart disease or disorder is myocardial infarction. In some embodiments, the heart disease or disorder is chronic myocardial infarction. In some embodiments, the heart disease or disorder is acute myocardial infarction. 
     In some embodiments, the disclosure provides a method of improving one or more symptoms of a heart disease or disorder in a subject comprising administration of a vector comprising an expression cassette described herein. In some embodiments, the symptoms are improved compared to the symptoms of the heart disease or disorder prior to administration of the vector to the subject. In some embodiments, the disclosure provides a method of improving one or more symptoms of a heart disease or disorder in a subject comprising administration of an rAAV virion described herein. In some embodiments, the symptoms are improved compared to the symptoms of the heart disease or disorder prior to administration of the rAAV virion to the subject. In some embodiments, the heart disease or disorder is heart failure. In some embodiments, the heart disease or disorder is cardiomyopathy. In some embodiments, the heart disease or disorder is dilated cardiomyopathy. In some embodiments, the heart disease or disorder is myocardial infarction. In some embodiments, the heart disease or disorder is chronic myocardial infarction. In some embodiments, the heart disease or disorder is acute myocardial infarction. 
     In some embodiments, the disclosure provides a method of preventing one or more symptoms of a heart disease or disorder in a subject comprising administration of a vector comprising an expression cassette described herein. In some embodiments, the disclosure provides a method of preventing one or more symptoms of a heart disease or disorder in a subject comprising administration of the rAAV virion described herein. In some embodiments, the symptoms are prevented in a subject considered to be at-risk of the heart disease or disorder. In some embodiments, the heart disease or disorder is heart failure. In some embodiments, the heart disease or disorder is cardiomyopathy. In some embodiments, the heart disease or disorder is dilated cardiomyopathy. In some embodiments, the heart disease or disorder is myocardial infarction. In some embodiments, the heart disease or disorder is chronic myocardial infarction. In some embodiments, the heart disease or disorder is acute myocardial infarction. 
     In some embodiments, the symptoms are reduced compared to the symptoms of the heart disease or disorder prior to administration of the vector to the subject. In some embodiments, the symptoms are reduced compared to the symptoms of the heart disease or disorder prior to administration of the rAAV virion to the subject. In some embodiments, the heart disease or disorder is heart failure. In some embodiments, the heart disease or disorder is cardiomyopathy. In some embodiments, the heart disease or disorder is dilated cardiomyopathy. In some embodiments, the heart disease or disorder is myocardial infarction. In some embodiments, the heart disease or disorder is chronic myocardial infarction. In some embodiments, the heart disease or disorder is acute myocardial infarction. 
     As used herein, “symptoms” include any of the diagnostic criteria or symptoms associated with, e.g., heart diseases described herein. Severity and changes of symptoms and diagnostic results are determined by a medical professional qualified to deliver assessments and analyze the results of such assessments. 
     Common symptoms in subjects with or at risk of developing heart disease are fatigue, dyspnea, edema, chest pain, arrhythmias, blood clots, impaired heart valve function, and heart murmur. In some embodiments, the subject experiences reduced symptoms associated with the heart diseases described herein following administration of the vector, an rAAV virion or compositions of the disclosure. In some embodiments, the improved symptoms are one or more of enhanced contractility; reduced fatigue; reduced dyspnea; reduced edema; reduced chest pain; reduced arrhythmias; reduced blood clots; improved heart valve function; and reduced heart murmur. In some embodiments, the symptom is a change in 6 minute walk distance. In some embodiments, symptoms are determined by the Minnesota Living with Heart Failure Questionnaire. In some embodiments, the symptom is an abnormal level of B-type natriuretic peptide (i.e., BNP, NT-proBNP). In some embodiments, the severity of symptoms are determined by measuring LV remodeling. In some embodiments of the method described herein improves one or more measures of cardiac function. In some embodiments, the measures of cardiac function comprise fractional shortening and/or left ventricular internal dimension (LVID). In some embodiments, the measures of cardiac function comprises left ventricular end-systolic volume (LVESV). In some embodiments, the improvement in cardiac function is ejection fraction. In some embodiments, improvement in cardiac function is observed at weeks 2 through 12. In some embodiments, the method reduces cardiac remodeling. In some embodiments, the method counteracts a decrease in DWORF expression in subjects suffering from myocardial infarction. 
     Ejection fraction is a measurement of the percentage of blood leaving the heart each time it contracts. The ejection fraction is determined using the stroke volume (SV) and the end-diastolic volume (EDV), calculated as: EF(%)=(SV/EDV)×100. Ejection fraction can be measured in a subject with imaging tests, including echocardiogram, cardiac catheterization, magnetic resonance imaging (MRI), computerized tomography (CT), and/or nuclear medicine scan. A normal ejection fraction is between about 50% and about 75%. A “borderline” ejection fraction can range between about 41% and about 50%. A reduced ejection fraction is less than about 41%. A borderline or reduced ejection fraction can be used as a symptom in diagnosing a heart disease or disorder. It is understood that the cutoff values between normal, borderline, and reduced ejection fraction are approximate and one skilled in the art, e.g., a cardiologist, will ultimately make the determination. 
     In some embodiments of the methods provided herein, it may be desirable to improve ejection fraction. Ejection fraction can be considered to be improved if the ejection fraction percentage increases. In some embodiments, the ejection fraction 
     In some embodiments of the methods provided herein, it may be desirable to preserve ejection fraction. Preserving ejection fraction can be used to prevent the onset of a heart disease or disorder in a subject at risk thereof, prevent the progression of a heart disease or disorder, or prevent worsening of symptoms associated with a heart disease or disorder in a subject at risk of or suffering therefrom. 
     The disclosure provides methods of improving ejection fraction in a subject at risk or suffering from a heart disease or disorder. In some embodiments, ejection fraction is improved (i.e., increased) in the subject following administration of a vector comprising an expression cassette described herein. In some embodiments, ejection fraction is improved (i.e., increased) in the subject following administration of a vector or an rAAV virion described herein. In some embodiments, ejection fraction is improved about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 7 weeks, about 8 weeks, about 9 weeks, about 10 weeks, about 11 weeks, about 12 weeks, about 13 weeks, about 14 weeks, about 15 weeks, about 16 weeks, about 17 weeks, about 18 weeks, about 22 weeks or about 24 weeks following administration of the vector or the rAAV virion to the subject. In some embodiments, ejection fraction is improved about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% following administration of the vector or the rAAV virion to the subject. 
     The disclosure provides methods of preserving ejection fraction in a subject at risk or suffering from a heart disease or disorder. For example, the subject may maintain an ejection fraction that would otherwise be expected to reduce in the absence of administration of the vector or the rAAV virion or pharmaceutical composition of the disclosure. In some embodiments, ejection fraction is preserved in the subject following administration of the vector or the rAAV virion of the disclosure. In some embodiments, ejection fraction is preserved about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 7 weeks, about 8 weeks, about 9 weeks, about 10 weeks, about 11 weeks, about 12 weeks, about 13 weeks, about 14 weeks, about 15 weeks, about 16 weeks, about 17 weeks, about 18 weeks, about 22 weeks or about 24 weeks following administration of the vector or rAAV virion to the subject. In some embodiments, ejection fraction is preserved by about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% following administration of the vector or rAAV virion to the subject. 
     Assessment of heart contractility can be used to assess acute and chronic forms of heart failure. Heart contractility may be monitored by using invasive hemodynamic monitoring, continuous ECG monitoring, central venous pressure, kidney function, pulse oximetry, arterial pressure monitoring, pulmonary artery catheter, and/or transeophageal echocardiography (Kuhn C, Werdan K.  Surgical Treatment: Evidence - Based and Problem - Oriented.  Munich: Zuckschwerdt; 2001. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6895/). 
     Dyspnea and fatigue associated with heart disease described herein can be measured using questionnaires. The Modified Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ-M)10 (Huang et al.  Am J Crit Care.  17:436-442 (2008)) and Minnesota Living with Heart Failure Questionnaire (MLHFQ)11 (Bilbao et al.  Health Qual Life Outcomes.  14:23 (2016)), for example, can be used to measure subjects with a heart disease as described herein. The questionnaires are self-administered and allow a score to be derived that is used to assess symptom severity for dyspnea, fatigue, and other heart-health related symptoms. 
     Cardiomyopathy, myocardial infarction and heart valve function may be assessed using one or more of an exercise stress test, electrocardiogram, echocardiogram, chest X-ray, cardiac CT scan, or angiogram with cardiac catheterization, cardiac MRI, B-type natriuretic peptide (BNP) levels in the blood, and/or genetic screening. Further testing is required to diagnose specific types of cardiomyopathy, myocardial infarction, or heart valve dysfunction. 
     In some aspects, administration of a vector comprising an expression cassette described herein to a subject results in an improvement in exercise capacity of the subject (e.g., improvement in running distance and/or time to exhaustion). In some aspects, administration of an rAAV comprising an expression cassette described herein encoding DWORF to a subject results in an improvement in exercise capacity of the subject (e.g., improvement in running distance and/or time to exhaustion). 
     Dilated cardiomyopathy (DCM) is a progressive disease of heart muscle characterized by chamber enlargement and contractile dysfunction of the left ventricle in the absence of chronic pressure and/or volume overload. DCM is diagnosed primarily using echocardiography. 
     Echocardiography with a PLAX view in 2D/M-mode is used to measure several parameters, including ejection fraction, LVIDd/s, IVSd, LVPWd, and fractional shortening. These parameters are used to assess the left ventricle cavity size, wall thickness, and radial function. Diagnostic criterion for DCM includes LVIDd/s greater than 112% (2 S.D) corrected for age and body surface area (BSA). Fractional shortening less than 25% is a criterion for the diagnosis of DCM in the presence of a dilated ventricle (Mathew et al.  Echo Res Pract.  4:G-1-G13 (2017)). 
     Qualitative assessment of left and right ventricular structure and function with special reference to radial and longitudinal function and regional wall motion abnormalities are assessed by echocardiography in the apical four-chamber (A4C) view in 2D mode. Ejection fraction (EF) can be estimated using, for example, biplane Simpsons method. EF of less than 45% is a diagnostic criterion for DCM in the presence of dilated ventricle (Mathew et al.  Echo Res Pract.  4: G1-G13 (2017)). 
     Administration 
     In some embodiments, the vectors and compositions of the present disclosure can be administered to a subject in need thereof by systemic application, e.g., by intravenous, intra-arterial or intraperitoneal delivery. In some embodiments, the rAAV virion and compositions of the present disclosure can be administered to a subject in need thereof by systemic application, e.g., by intravenous, intra-arterial or intraperitoneal delivery of a vector in analogy to what has been shown in animal models (Katz et al.,  Gene Ther  19:659-669 (2012)). In some embodiments, the vectors, rAAV virions and compositions of the present disclosure treat or prevent heart failure. In some embodiments, the cardiomyopathy, wherein the vector is administered systemically. In some embodiments, the rAAV virion is administered by intravenous or intracoronary injection. 
     The disclosure provides methods for expressing a polypeptide in a cell in vitro, ex vivo, or in vivo. In some embodiments, the disclosure provides methods for expressing a DWORF polypeptide in a cell in vitro, ex vivo, or in vivo. The method comprises, for example, exposing a target cell to the vectors, rAAV virions or pharmaceutical compositions described herein. A target cell can be, for example and without limitation, a cardiac cell, a muscle cell, an induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM), and/or a cardiomyocyte. In some embodiments, a method of expressing a polypeptide (e.g., DWORF polypeptide) in a cell comprises transfecting or transducing (alternating referred to as “infecting”) a target cell or population of target cells with a vector described herein. In some embodiments, a method of expressing a polypeptide (e.g., DWORF polypeptide) in a cell comprises transducing (alternating referred to as “infecting”) a target cell or population of target cells with an rAAV virion or pharmaceutical compositions described herein. In some embodiments, the rAAV transduces cardiac cells. In some embodiments, the rAAV transduces cardiomyocytes. In some embodiments, the rAAV transduces induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM). 
     In some embodiments, the vector transfection or transduction increases polypeptide expression in the heart of the subject. In some embodiments, the rAAV transduction increases DWORF polypeptide expression in the heart of the subject. “Increased polypeptide expression” typically refers to expression at least 5%, 10%, 15%, 20% or more compared to a control subject or tissue not treated with the vector. “Increased DWORF polypeptide expression” typically refers to expression at least 5%, 10%, 15%, 20% or more compared to a control subject or tissue not treated with the vector. In some embodiments, detectable expression means expression at 1.5-fold, 2-fold, 2.5-fold, or 3-fold greater than a no-vector control. Expression can be assessed by Western blot, as described in the example that follows, or enzyme-linked immunosorbent assay (ELISA), or other methods known in the art. In some cases, expression is measured quantitatively using a standard curve. Standard curves can be generated using purified protein, e.g., purified DWORF polypeptide, by methods described in the examples or known in the art. Alternatively, expression of the therapeutic gene product can be assessed by quantification of the corresponding MRNA. In some embodiments, the method causes the expression of the polypeptide (e.g, DWORF polypeptide) in the heart of the subject. 
     In some embodiments, the method causes no detectable expression of the polypeptide in the muscles of the subject except the heart, in the liver of the subject, and/or in cardiac fibroblasts. In some embodiments, the method causes expression of the polypeptide in cardiomyocytes. 
     In some embodiments, the method causes no detectable expression of the DWORF polypeptide in the muscles of the subject except the heart. In some embodiments, the method causes no detectable expression of the DWORF polypeptide in the liver of the subject. In some embodiments, the method causes expression of the DWORF polypeptide in cardiomyocytes. In some embodiments, the method causes no detectable expression of the DWORF polypeptide in cardiac fibroblasts. 
     In some embodiments, the increased polypeptide expression in heart tissue occurs at doses, in vector genomes (vg) per kilogram weight of subject (kg), of 3×10 14  vg/kg or less, 2×10 14  vg/kg or less, 1×10 14  vg/kg, or less, 9×10 13  vg/kg or less, 8×10 13  vg/kg or less, 7×10 13  vg/kg or less, 6×10 13  vg/kg or less, 5×10 13  vg/kg or less, 4×10 13  vg/kg or less, 3×10 13  vg/kg or less, 2×10 13  vg/kg or less, or 1×10 13  vg/kg or less. 
     In some embodiments, the increased DWORF expression in heart tissue occurs at doses, in vector genomes (vg) per kilogram weight of subject (kg), of 3×10 14  vg/kg or less, 2×10 14  vg/kg or less, 1×10 14  vg/kg or less, 9×10 13  vg/kg or less, 8×10 13  vg/kg or less, 7×10 13  vg/kg or less, 6×10 13  vg/kg or less. 5×10 13  vg/kg or less, 4×10 13  vg/kg or less, 3×10 13  vg/kg or less, 2×10 13  vg/kg or less, or 1×10 13  vg/kg or less. 
     Pharmaceutical Compositions and Kits 
     The vectors of the disclosure are generally delivered to the subject as a pharmaceutical composition. In some embodiments, the rAAV virion of the disclosure is delivered to the subject as a pharmaceutical composition. Pharmaceutical compositions comprise a pharmaceutically acceptable solvent (e.g., water, etc.) and one or more excipients. In some embodiments, the pharmaceutical compositions comprise a buffer at about neutral pH (pH 5, 6, 7, 8, or 9). In some embodiments, the pharmaceutical composition comprises phosphate buffered saline (e.g., PBS at pH of about 7). The pharmaceutical compositions may comprise a pharmaceutically acceptable salt. The concentration of the salt may be selected to ensure that the pharmaceutical composition is isotonic to, or nearly isotonic to, the target tissue. 
     In various embodiments, the compositions described herein contain vehicles (e.g., carriers, diluents and excipients) that are pharmaceutically acceptable for a formulation capable of being injected. These may be in particular isotonic, sterile, saline solutions (monosodium or disodium phosphate, sodium, potassium, calcium or magnesium chloride and the like or mixtures of such salts), or dry, especially freeze-dried compositions which upon addition, depending on the case, of sterilized water or physiological saline, permit the constitution of injectable solutions. Illustrative pharmaceutical forms suitable for injectable use include, e.g., sterile aqueous solutions or dispersions; formulations including sesame oil, peanut oil or aqueous propylene glycol; and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. 
     In various embodiments, the pharmaceutical compositions of the disclosure comprise about 1×10 8  genome copies per milliliter (GC/mL), about 5×10 8  GC/mL, about 1×10 9  GC/mL, about 5×10 9  GC/mL, about 1×10 10  GC/mL, about 5×10 10  GC/mL, about 1×10 11  GC/mL, about 5×10 11  GC/mL, about 1×10 12  GC/mL, about 5×10 12  GC/mL, about 5×10 13  GC/mL, about 1×10 14  GC/mL, or about 5×10 14  GC/mL of the viral vector (e.g., rAAV virion). 
     In various embodiments, the pharmaceutical compositions of the disclosure comprise about 1×10 8  viral genomes per milliliter (vg/mL), about 5×10 8  vg/mL, about 1×10 9  vg/mL, about 5×10 9  vg/mL, about 1×10 10  vg/mL, about 5×10 10  vg/mL, about 1×10 11  vg/mL, about 5×10 11  vg/mL, about 1×10 12  vg/mL, about 5×10 12  vg/mL, about 5×10 13  vg/mL, about 1×10 14  vg/mL, or about 5×10 14  vg/mL of the viral vector (e.g., rAAV virion). 
     In some embodiments, the pharmaceutical compositions of the disclosure are administered in a total volume of about 1 mL, 5 mL, 10 mL, about 20 mL, about 25mL, about 30 mL, about 35 mL, about 40 mL, about 45 mL, about 50 mL, about 55 mL, about 60 mL, 65 mL, about 70 mL, about 75 mL, about 80 mL, about 85 mL, about 90 mL, about 95 mL, about 100 mL, about 105 mL, about 110 mL, about 115 mL, about 120 mL, about 125 mL, about 130 mL, about 135 mL, about 140 mL, about 145 mL, about 150 mL, about 155 mL, about 160 mL, about 165 mL, about 170 mL, about 175 mL, about 180 mL, about 185 mL, about 190 mL, about 200 mL, about 205 mL, about 210 mL, about 215 mL, or about 220 mL. 
     Genome copies per milliliter can be determined by quantitative polymerase change reaction (qPCR) using a standard curve generated with a reference sample having a known concentration of the polynucleotide genome of the virus. For AAV, the reference sample used is often the transfer plasmid used in generation of the rAAV virion but other reference samples may be used. 
     Alternatively or in addition, the concentration of a viral vector can be determined by measuring the titer of the vector on a cell line. Viral titer is typically expressed as viral particles (vp) per unit volume (e.g., vp/mL). In various embodiments, the pharmaceutical compositions of the disclosure comprise about 1×10 8  viral particles per milliliter (vp/mL), about 5×10 8  vp/mL, about 1×10 9  vp/mL, about 5×10 9  vp/mL, about 1×10 10  vp/mL, about 5×10 10  vp/mL, about 1×10 11  vp/mL, about 5×10 11  vp/mL, about 1×10 12  vp/mL, about 5×10 12  vp/mL, about 5×10 13  vp/mL, or about 1×10 14  vp/mL, or about 5×10 14  of the viral vector (e.g., rAAV virion). 
     In some embodiments, the present disclosure provides a kit comprising a container housing a pharmaceutical composition as described herein. 
     Numbered Embodiments of the Invention I 
     Embodiment 1: A recombinant adeno-associated virus (rAAV) virion, comprising a capsid protein and a viral genome comprising an expression cassette comprising a polynucleotide sequence encoding a dwarf open reading frame (DWORF) polypeptide operatively linked to a promoter, the expression cassette flanked by inverted terminal repeats. 
     Embodiment 2: The rAAV virion of embodiment 1, wherein the DWORF polypeptide shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 1, 3, 4, 7, 9, 23, and 43. 
     Embodiment 3: The rAAV virion of embodiment 1, wherein the DWORF polypeptide is selected from SEQ ID NOs: 1, 3, 4, 7, 9, 23, and 43. 
     Embodiment 4: The rAAV virion of embodiment 1 or 2, wherein the promoter is a chicken cTnT promoter. 
     Embodiment 5: The rAAV virion of embodiment 4, wherein the chicken cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 11. 
     Embodiment 6: The rAAV virion of embodiment 4, wherein the chicken cTnT promoter comprises SEQ ID NO: 11. 
     Embodiment 7: The rAAV virion of embodiment 1 or 2, wherein the promoter is a human cTnT promoter. 
     Embodiment 8: The rAAV virion of embodiment 7, wherein the human cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 12 or SEQ II) NO: 13. 
     Embodiment 9: The rAAV virion of embodiment 7, wherein the human cTnT promoter comprises SEQ ID NO: 12 or SEQ ID NO: 13. 
     Embodiment 10: The rAAV virion of any one of embodiments 1 to 9, wherein the expression cassette further comprises one or more enhancers. 
     Embodiment 11: The rAAV virion of embodiment 10, wherein the enhancer the one or more enhancers are selected from a ACTC1 cardiac enhancer and a αMHC enhancer. 
     Embodiment 12: The rAAV virion of embodiment 11, wherein the ACTC1 cardiac enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 78. 
     Embodiment 13: The rAAV virion of embodiment 11, wherein the ACTC1 cardiac enhancer comprises SEQ ID NO: 78. 
     Embodiment 14: The rAAV virion of embodiment 11, wherein the αMHC enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 79. 
     Embodiment 15: The rAAV virion of embodiment 11, wherein the αMHC enhancer comprises SEQ ID NO: 79. 
     Embodiment 16: The rAAV virion of any one of embodiments 1 to 15, wherein the expression cassette further comprises an intron. 
     Embodiment 17: The rAAV virion of embodiment 16, wherein the intron is selected from a CMV intron and a chimeric intron. 
     Embodiment 18: The rAAV virion of embodiment 17, wherein the CMV intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. 
     Embodiment 19: The rAAV virion of embodiment 17, wherein the CMV intron comprises SEQ ID NO: 80. 
     Embodiment 20: The rAAV virion of embodiment 17, wherein the chimeric intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81. 
     Embodiment 21: The rAAV virion of embodiment 17, wherein the chimeric intron comprises SEQ ID NO: 81. 
     Embodiment 22: The rAAV virion of any one of embodiments 1 to 21, wherein the expression cassette further comprises a WPRE sequence. 
     Embodiment 23: The rAAV virion of embodiment 22, wherein the WPRE sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 26. 
     Embodiment 24: The rAAV virion of embodiment 22, wherein the WPRE sequence comprises SEQ ID NO: 26. 
     Embodiment 25: The rAAV virion of any one of embodiments 1 to 24, wherein the expression cassette further comprises a polyadenylation sequence. 
     Embodiment 26: The rAAV virion of embodiment 25, wherein the polyadenylation sequence is selected from a BGH polyadenylation sequence and a SV40 polyadenylation sequence. 
     Embodiment 27: The rAAV virion of embodiment 26, wherein the BGH polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 27. 
     Embodiment 28: The rAAV virion of embodiment 26, wherein the BGH polyadenylation sequence comprises SEQ ID NO: 27. 
     Embodiment 29: The rAAV virion of embodiment 26, wherein the SV40 polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 28. 
     Embodiment 30: The rAAV virion of embodiment 26, wherein the SV40 polyadenylation sequence comprises SEQ ID NO: 28. 
     Embodiment 31: The rAAV virion of any one of embodiments 1 to 30, wherein the expression cassette is flanked by ITRs. 
     Embodiment 32: The rAAV virion of embodiment 31, wherein the ITRs share at least 90%, 95%, 96%, 97%, 98%, or 99% identity to one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     Embodiment 33: The rAAV virion of embodiment 31, wherein the ITRs comprise one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     Embodiment 34: The rAAV virion of any one of embodiments 1 to 33, wherein the expression cassette comprises a single promoter. 
     Embodiment 35: The rAAV virion of any one of embodiments 1 to 33, wherein the expression cassette comprises two promoters. 
     Embodiment 36: The rAAV virion of any one of embodiments 1 to 35 wherein the expression cassette comprises a single copy a sequence encoding the DWORF polypeptide. 
     Embodiment 37: The rAAV virion of any one of embodiments 1 to 35 wherein the expression cassette comprises two copies of a sequence encoding the DWORF polypeptide. 
     Embodiment 38: The rAAV virion of any one of embodiments 1 to 37 wherein the expression cassette comprises one, two, three, or four enhancers. 
     Embodiment 39: The rAAV virion of any one of embodiments 1 to 38 wherein the expression cassette comprises one or two introns. 
     Embodiment 40: The rAAV virion of any one of embodiments 1 to 39 wherein the expression cassette comprises one or two WPRE sequences. 
     Embodiment 41: The rAAV virion of any one of embodiments 1 to 40 wherein the expression cassette comprises one or two polyadenylation sequences. 
     Embodiment 42: The rAAV virion of any one of embodiments 1 to 41 wherein the expression cassette comprises about 3.2 kb, about, about 3.3 kb, about 3.4 kb, about 3.5 kb, about 3.6 kb, about 3.7 kb, or less. 
     Embodiment 43: The rAAV virion of any one of embodiments 1 to 41 wherein the expression cassette comprises about 1.9 kb, about 2.1 kb, about 2.2 kb, about 2.3 kb, about 2.4 kb, about 2.5 kb, about 2.6 kb, about 2.7 kb, about 2.8 kb, about 2.9 kb, about 3.0 kb, about 3.1 kb, about 3.2 kb, or more. 
     Embodiment 44: The rAAV virion of embodiment 1, wherein the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75. 
     Embodiment 45: The rAAV virion of embodiment 1, wherein the expression cassette comprises any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75. 
     Embodiment 46: The rAAV virion of embodiment 1, wherein the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 61. 
     Embodiment 47: The rAAV virion of embodiment 1, wherein the expression cassette comprises SEQ ID NO: 61. 
     Embodiment 48: The rAAV virion of embodiment 1, wherein the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 62. 
     Embodiment 49: The rAAV virion of embodiment 1, wherein the expression cassette comprises SEQ ID NO: 62. 
     Embodiment 50: The rAAV virion of embodiment 1, wherein the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 63. 
     Embodiment 51: The rAA virion of embodiment 1, wherein the expression cassette comprises SEQ ID NO: 63. 
     Embodiment 52: The rAAV virion of any one of embodiments 1 to 51, wherein the capsid protein shares at least 98%, at least 99%, or 100% identity to an AAV9 capsid protein (SEQ ID NO: 143). 
     Embodiment 53: The rAAV virion of any one of embodiments 1 to 51, wherein the capsid protein shares at least 98%, at least 99%, or 100% identity to an AAV5 capsid protein (SEQ ID NO: 144). 
     Embodiment 54: The rAAV virion of any one of embodiments 1 to 51, wherein the capsid protein is a chimeric capsid protein. 
     Embodiment 55: The rAAV virion of any one of embodiments 1 to 51, wherein the capsid protein is an AAV5/AAV9 chimeric capsid protein. 
     Embodiment 56: The rAAV virion of any one of embodiments 1 to 51, wherein the capsid protein is selected from any one of SEQ ID NOs: 145-200. 
     Embodiment 57: An expression cassette comprising polynucleotide sequence encoding a dwarf open reading frame (DWORF) polypeptide operatively linked to a promoter. 
     Embodiment 58: The expression cassette of embodiment 57, wherein the DWORF polypeptide is selected from SEQ ID NOs: 1, 3, 4, 7, 9, 23, and 43. 
     Embodiment 59: The expression cassette of embodiment 57 or 58, wherein the promoter is a chicken cTnT promoter. 
     Embodiment 60: The expression cassette of embodiment 59, wherein the chicken cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 11. 
     Embodiment 61: The expression cassette of embodiment 59, wherein the chicken cTnT promoter comprises SEQ ID NO: 11. 
     Embodiment 62: The expression cassette of embodiment 57 or 58, wherein the promoter is a human cTnT promoter. 
     Embodiment 63: The expression cassette of embodiment 62, wherein the human cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 12 or SEQ ID NO: 13. 
     Embodiment 64: The expression cassette of embodiment 62, wherein the human cTnT promoter comprises SEQ ID NO: 12 or SEQ ID NO: 13. 
     Embodiment 65: The expression cassette of any one of embodiments 57 to 64, wherein the expression cassette further comprises one or more enhancers. 
     Embodiment 66: The expression cassette of embodiment 65, wherein the enhancer the one or more enhancers are selected from a ACTC1 cardiac enhancer and a αMHC enhancer. 
     Embodiment 67: The expression cassette of embodiment 66, wherein the ACTC1 cardiac enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 78. 
     Embodiment 68: The expression cassette of embodiment 66, wherein the ACTC1 cardiac enhancer comprises SEQ ID NO: 78. 
     Embodiment 69: The expression cassette of embodiment 66, wherein the αMHC enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 79. 
     Embodiment 70: The expression cassette of embodiment 66, wherein the αMHC enhancer comprises SEQ ID NO: 79. 
     Embodiment 71: The expression cassette of any one of embodiments 57 to 70, wherein the expression cassette further comprises an intron. 
     Embodiment 72: The expression cassette of any one of embodiments 57 to 70, wherein the intron is selected from a CMV intron and a chimeric intron. 
     Embodiment 73: The expression cassette of embodiment 72, wherein the CMV intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. 
     Embodiment 74: The expression cassette of embodiment 72, wherein the CMV intron comprises SEQ ID NO: 80. 
     Embodiment 75: The expression cassette of embodiment 72, wherein the chimeric intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81. 
     Embodiment 76: The expression cassette of embodiment 72, wherein the chimeric intron comprises SEQ ID NO: 81. 
     Embodiment 77: The expression cassette of any one of embodiments 57 to 76, wherein the expression cassette further comprises a WPRE sequence. 
     Embodiment 78: The expression cassette of embodiment 77, wherein the WPRE sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 26. 
     Embodiment 79: The expression cassette of embodiment 77, wherein the WPRE sequence comprises SEQ ID NO: 26. 
     Embodiment 80: The expression cassette of any one of embodiments 57 to 79, wherein the expression cassette further comprises a polyadenylation sequence. 
     Embodiment 81: The expression cassette of embodiment 80, wherein the polyadenylation sequence is selected from a BGH polyadenylation sequence and a SV40 polyadenylation sequence. 
     Embodiment 82: The expression cassette of embodiment 81, wherein the BGH polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 27. 
     Embodiment 83: The expression cassette of embodiment 81, wherein the BGH polyadenylation sequence comprises SEQ ID NO: 27. 
     Embodiment 84: The expression cassette of embodiment 81, wherein the SV40 polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 28. 
     Embodiment 85: The expression cassette of embodiment 81, wherein the SV40 polyadenylation sequence comprises SEQ ID NO: 28. 
     Embodiment 86: The expression cassette of any one of embodiments 57 to 85, wherein the expression cassette is flanked by ITRs. 
     Embodiment 87: The expression cassette of embodiment 86, wherein the ITRs share at least 90%, 95%, 96%, 97%, 98%, or 99% identity to one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     Embodiment 88: The expression cassette of embodiment 86, wherein the ITRs comprise one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     Embodiment 89: The expression cassette of any one of embodiments 57 to 88 comprising a single promoter. 
     Embodiment 90: The expression cassette of any one of embodiments 57 to 88 comprising two promoters. 
     Embodiment 91: The expression cassette of any one of embodiments 57 to 90 comprising a single copy a sequence encoding the DWORF polypeptide. 
     Embodiment 92: The expression cassette of any one of embodiments 57 to 90 comprising two copies of a sequence encoding the DWORF polypeptide. 
     Embodiment 93: The expression cassette of any one of embodiments 57 to 92 comprising one, two, three, or four enhancers. 
     Embodiment 94: The expression cassette of any one of embodiments 57 to 93 comprising one or two introns. 
     Embodiment 95: The expression cassette of any one of embodiments 57 to 94 comprising one or two WPRE sequences. 
     Embodiment 96: The expression cassette of any one of embodiments 57 to 95 comprising one or two polyadenylation sequences. 
     Embodiment 97: The expression cassette of any one of embodiments 57 to 96 comprising about 3.2 kb, about, about 3.3 kb, about 3.4 kb, about 3.5 kb, about 3.6 kb, about 3.7 kb, or less. 
     Embodiment 98: The expression cassette of any one of embodiments 57 to 96 comprising about 1.9 kb, about 2.1 kb, about 2.2 kb, about 2.3 kb, about 2.4 kb, about 2.5 kb, about 2.6 kb, about 2.7 kb, about 2.8 kb, about 2.9 kb, about 3.0 kb, about 3.1 kb, about 3.2 kb, or more. 
     Embodiment 99: The expression cassette of embodiment 1, comprising a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75. 
     Embodiment 100: The expression cassette of embodiment 57, comprising any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75. 
     Embodiment 101: The expression cassette of embodiment 57, comprising a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 61. 
     Embodiment 102: The expression cassette of embodiment 57, comprising SEQ ID NO: 61. 
     Embodiment 103: The expression cassette of embodiment 57, comprising a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 62. 
     Embodiment 104: The expression cassette of embodiment 57, comprising SEQ ID NO: 62. 
     Embodiment 105: The expression cassette of embodiment 57, comprising a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 63. 
     Embodiment 106: The expression cassette of embodiment 57, comprising SEQ ID NO: 63. 
     Embodiment 107: The expression cassette of any one of embodiments 57 to 98, further comprising a 5′ inverted terminal repeat and a 3′ inverted terminal repeat. 
     Embodiment 108: A pharmaceutical composition comprising the rAAV virion of any one of embodiments 1 to 56 and an pharmaceutically acceptable diluent. 
     Embodiment 109: A kit comprising the pharmaceutical composition of embodiment 108. 
     Embodiment 110: A method of increasing DWORF expression in a cell comprising contacting a cell with the rAAV virion of any one of embodiments 1 to 56 or the composition of embodiment 108. 
     Embodiment 111: The method of embodiment 110, wherein the cell is a cardiac cell. 
     Embodiment 112: The method of embodiment 111, wherein the cardiac cell is a cardiomyocyte. 
     Embodiment 113: The method of any one of embodiments 110 to 112, wherein DWORF expression is increased between about 1.5-fold and 150-fold. 
     Embodiment 114: The method of any one of embodiments 110 to 113, wherein the contacting is in vitro. 
     Embodiment 115: The method of any one of embodiments 110 to 113, wherein the contacting is in vivo. 
     Embodiment 116: A method of increasing DWORF expression in a tissue comprising contacting the tissue with the rAAV virion of any one of embodiments 1 to 56 or the composition of embodiment 108. 
     Embodiment 117: The method of embodiment 116, wherein the tissue is cardiac tissue. 
     Embodiment 118: The method of embodiment 116 or 117, wherein DWORF expression is increased between about 1.5-fold and 150-fold. 
     Embodiment 119: The method of any one of embodiments 116 to 118, wherein the contacting is in vitro. 
     Embodiment 120: The method of embodiment 116 or 118, wherein the contacting is in vivo. 
     Embodiment 121: A method of increasing DWORF expression in an organ comprising contacting the organ with the rAAV virion of any one of embodiments 1 to 56 or the composition of embodiment 108. 
     Embodiment 122: The method of embodiment 121, wherein the organ is a heart. 
     Embodiment 123: The method of embodiment 122, wherein the heart is diseased or is at risk of disease. 
     Embodiment 124: The method of embodiment 122, or embodiment 123, wherein the heart has reduced or borderline ejection fraction. 
     Embodiment 125: The method of embodiment 122 or embodiment 123, wherein the heart has a normal ejection fraction. 
     Embodiment 126: The method of any one of embodiments 122 to 125, wherein the heart comprises a genetic mutation associated with a heart disease. 
     Embodiment 127: The method of embodiment 126, wherein the genetic mutation is a PLN mutation. 
     Embodiment 128: The method of any one of embodiments 121 to 127, wherein the heart has low or undetectable DWORF expression compared to a healthy heart. 
     Embodiment 129: The method of any one of embodiments 121 to 128, wherein DWORF expression is increased between about 1.5-fold and 150-fold. 
     Embodiment 130: The method of any one of embodiments 121 to 129, wherein the contacting is in vitro. 
     Embodiment 131: The method of any one of embodiments 121 to 129, wherein the contacting is in vivo. 
     Embodiment 132: A method of increasing DWORF expression in an subject comprising administering to the subject the rAAV virion of any one of embodiments 1 to 56 or the composition of embodiment 108. 
     Embodiment 133: The method of embodiment 132, wherein the subject is an animal. 
     Embodiment 134: The method of embodiment 132, wherein the subject is a human. 
     Embodiment 135: The method of any one of embodiments 132 to 134, wherein DWORF expression is increased in the heart of the subject. 
     Embodiment 136: The method of any one of embodiments 132 to 135, wherein subject has a heart disease or is at risk of a heart disease. 
     Embodiment 137: The method of any one of embodiments 132 to 136, wherein subject has borderline or reduced ejection fraction. 
     Embodiment 138: The method of any one of embodiments 132 to 136, wherein the subject has normal ejection fraction. 
     Embodiment 139: The method of any one of embodiments 132 to 138, wherein the subject has a genetic mutation associated with a heart disease. 
     Embodiment 140: The method of embodiment 139, wherein the genetic mutation is a PLN mutation. 
     Embodiment 141: The method of any one of embodiments 132 to 140, wherein the subject has a low or undetectable level of DWORF expression compared to a healthy subject. 
     Embodiment 142: A method of treating a heart disease or disorder in a subject in need thereof comprising administering to the subject the rAAV virion of any one of embodiments 1 to 56 or the composition of embodiment 108. 
     Embodiment 143: The method of embodiment 142, wherein the subject has a heart disease or disorder. 
     Embodiment 144: The method of embodiment 142, wherein the subjectis a risk of developing a heart disease or disorder. 
     Embodiment 145: The method or any one of embodiments 142 to 144, wherein the heart disease or disorder is cardiomyopathy. 
     Embodiment 146: The method of any one of embodiments 142 to 144, wherein the heart disease or disorder is dilated cardiomyopathy. 
     Embodiment 147: The method of any one of embodiments 142 to 144, wherein the heart disease or disorder is myocardial infarction. 
     Embodiment 148: The method of any one of embodiments 142 to 144, wherein the heart disease or disorder is chronic myocardial infarction. 
     Embodiment 149: The method of any one of embodiments 142 to 144, wherein the heart disease or disorder is acute myocardial infarction. 
     Embodiment 150: The method of any one of embodiments 142 to 149, wherein the subject has an inherited risk allele for a heart disease or disorder. 
     Embodiment 151: The method of any one of embodiments 142 to 150, wherein the inherited risk allele comprises a mutation to the PLN gene. 
     Embodiment 152: The method of embodiment 151, wherein the mutation to the PLN gene is a PLN promoter mutation. 
     Embodiment 153: The method of embodiment 151, wherein the mutation to the PLN gene is a PLN L39stop  mutation. 
     Embodiment 154: The method of embodiment 151, wherein the mutation to the PLN gene is a RC9 mutation. 
     Embodiment 155: The method of embodiment 151, wherein the mutation to the PLN gene is a R9L mutation. 
     Embodiment 156: The method of embodiment 151, wherein the mutation to the PLN gene is a PLN gene duplication. 
     Embodiment 157: The method of embodiment 151, wherein the mutation to the PLN gene is a R14del mutation. 
     Embodiment 158: The method of any one of embodiments 142 to 157, wherein the heart disease or disorder is with reduced ejection fraction (HFrEF). 
     Embodiment 159: The method of any one of embodiments 142 to 157, wherein the heart disease of disorder is with preserved ejection fraction (HFpEF). 
     Embodiment 160: The method of any one of embodiments 142 to 159, wherein the method causes expression of the DWORF polypeptide in the heart of the subject. 
     Embodiment 161: The method of any one of embodiments 142 to 160, wherein the method causes expression of the DWORF polypeptide in cardiomyocytes. 
     Embodiment 162: The method of any one of embodiments 142 to 161, wherein the method causes no detectable expression of the DWORF polypeptide in the muscles of the subject except the heart. 
     Embodiment 163: The method of any one of embodiments 142 to 162, wherein the method causes no detectable expression of the DWORF polypeptide in the liver of the subject. 
     Embodiment 164: The method of any one of embodiments 142 to 163, wherein the method causes no detectable expression of the DWORF polypeptide in cardiac fibroblasts. 
     Embodiment 165: The method of any one of embodiments 142 to 164, wherein the method improves one or more measures of cardiac function, optionally fraction shortening and/or left ventricular internal dimension (LVID). 
     Embodiment 166: The method of any one of embodiments 142 to 165, wherein the improvement in cardiac function is observed at weeks 2 through week 16. 
     Embodiment 167: The method of any one of embodiments 142 to 166, wherein the method reduces cardiac remodeling. 
     Embodiment 168: The method of any one of embodiments 142 to 166, wherein the method counteracts a decrease in DWORF expression in subjects suffering from or at risk of a heart disease. 
     Embodiment 169: The method of any one of embodiments 142 to 168, wherein the rAAV virion is administered by systemic administration. 
     Embodiment 170: The method of embodiment 169, wherein the systemic administration is selected from intravenous or intracoronary injection. 
     Embodiment 171: The method of embodiment 169 or 170, wherein the rAAV is administered as a unit dose. 
     Embodiment 172: The method of embodiment 171, wherein the unit dose comprises about 3×10 14  vg/kg or less, about 2×10 14  vg/kg or less, about 1×10 14  vg/kg or less, about 9×10 13  vg/kg or less, about 8×10 13  vg/kg or less, about 7×10 13  vg/kg or less, about 6×10 13  vg/kg or less, about 5×10 13  vg/kg or less, about 4×10 13  vg/kg or less, about 3×10 13  vg/kg, or less, about 2×10 13  vg/kg or less, or about 1×10 13  vg/kg or less. 
     Embodiment 173: A method of alleviating one or more symptoms of a heart disease or disorder in a subject in need thereof comprising administering the rAAV virion of any one of embodiments 1 to 56 or the composition of embodiment 108. 
     Embodiment 174: A method of improving one or more symptoms of a heart disease or disorder in a subject in need thereof comprising administering the rAAV virion of any one of embodiments 1 to 56 or the composition of embodiment 108. 
     Embodiment 175: A method of preventing one or more symptoms of a heart disease or disorder in a subject in need thereof comprising administering the rAAV virion of any one of embodiments 1 to 56 or the composition of embodiment 108. 
     Embodiment 176: An expression cassette comprising a polynucleotide comprising a 5′ to 3′ arrangement of elements, wherein the elements comprise:
         i. one or more promoters;   ii. optionally one or more enhancers;   iii. optionally one or more introns;   iv. one or more transgenes;   v. optionally one or more WPRE sequences; and   vi. optionally one or more polyadenylation sequences, p(A).       

     Embodiment 177: The expression cassette of embodiment 176, wherein the 5′ to 3′ arrangement of elements is selected from:
         i. 5′-promoter-intron-transgene-WPRE-p(A)-3′;   ii. 5′-enhancer-promoter-transgene-WPRE-p(A)-3′;   iii. 5′-enhancer-enhancer-promoter-transgene-WPRE-p(A)-3′;   iv. 5′-enhancer-enhancer-promoter-intron-transgene-WPRE-p(A)-3′;   v. 5′-enhancer-enhancer-promoter-intron-transgene-WPRE-p(A)-3′;   vi. 5′-enhancer-promoter-intron-transgene-WPRE-p(A)-p(A)-transgene-intron-promoter-enhancer-3′;   vii. 5′-enhancer-promoter-intron-transgene-WPRE-p(A)-enhancer-promoter-intron-transgene-p(A)-3′;   viii. 5′-p(A)-WPRE-transgene-intron-promoter-enhancer-enhancer-promoter-intron-transgene-p(A)-3′;   ix. 5′-promoter-intron-transgene-WPRE-p(A)-p(A)-transgene-intron-promoter-3′;   x. 5′-promoter-intron-transgene-WPRE-p(A)-promoter-intron-transgene-p(A)-3′; and   xi. 5′-p(A)-WPRE-transgene-intron-promoter-promoter-intron-transgene-p(A)-3′.       

     Embodiment 178: The expression cassette of embodiment 176 or embodiment 177, wherein the transgene has an increased expression level compared to a second expression cassette comprising a polynucleotide having an arrangement of elements from 5′ to 3′ comprising: 5′-promoter-transgene-WPRE-p(A)-3′. 
     Embodiment 179: The expression cassette of embodiment 178, wherein the increased expression level is between about 1.5-fold and about 150-fold compared to the second expression cassette. 
     Embodiment 180: A recombinant adeno-associated virus (rAAV) virion, comprising a capsid protein and a viral genome comprising an expression cassette of any one of embodiments 176 to 179, the expression cassette flanked by inverted terminal repeats. 
     Embodiment 181: The rAAV of embodiment 180, wherein the expression cassette comprises a transgene, wherein the transgene encodes a polypeptide use for treating or a preventing a heart disease, or alleviating symptoms associated with a heart disease. 
     Embodiment 182: The rAAV of embodiment 180 or embodiment 181, wherein the capsid protein is selected from any one of SEQ ID NOs: 145-200. 
     Numbered Embodiments of the Invention II 
     Embodiment 1: A recombinant adeno-associated virus (rAAV) virion, comprising a capsid protein and a viral genome comprising an expression cassette comprising a polynucleotide sequence encoding a polypeptide operatively linked to a promoter, the expression cassette flanked by inverted terminal repeats, optionally wherein the polypeptide is for expression in a cardiac cell or tissue and/or for use in treating or a preventing a heart disease. 
     Embodiment 2: The rAAV virion of embodiment 1, wherein the polypeptide is selected from DWORF, JPH2, BAG3, CRYAB, Lamin A isoform of LMNA, Lamin C isoform of LMNA, TNNI3, PLN, LAMP2a, LAMP2b, LAMP2c, DPI isoform of DSP, DPII isoform of DSP, DSG2, and JUP. 
     Embodiment 3: The rAAV virion of embodiment 1 or 2, wherein the polypeptide shares at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to a sequence selected from polypeptide sequences in Tables 2a and 2b. 
     Embodiment 4: The rAAV virion of any one of embodiments 1-3, wherein the promoter is a chicken cTnT promoter. 
     Embodiment 5: The rAAV virion of embodiment 4, wherein the chicken cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 11. 
     Embodiment 6: The rAAV virion of embodiment 4, wherein the chicken cTnT promoter comprises SEQ ID NO: 11. 
     Embodiment 7: The rAAV virion of any one of embodiments 1-3, wherein the promoter is a human cTnT promoter. 
     Embodiment 8: The rAAV virion of embodiment 7, wherein the human cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 12 or SEQ ID NO: 13. 
     Embodiment 9: The rAAV virion of embodiment 7, wherein the human cTnT promoter comprises SEQ ID NO: 12 or SEQ ID NO: 13. 
     Embodiment 10: The rAAV virion of any one of embodiments 1 to 9, wherein the expression cassette further comprises one or more enhancers. 
     Embodiment 11: The rAAV virion of embodiment 10, wherein the enhancer the one or more enhancers are selected from a ACTC1 cardiac enhancer and a αMHC enhancer. 
     Embodiment 12: The rAAV virion of embodiment 11, wherein the ACTC1 cardiac enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 78. 
     Embodiment 13: The rAAV virion of embodiment 11, wherein the ACTC1 cardiac enhancer comprises SEQ ID NO: 78. 
     Embodiment 14: The rAAV virion of embodiment 11, wherein the αMHC enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 79. 
     Embodiment 15: The rAAV virion of embodiment 11, wherein the αMHC enhancer comprises SEQ ID NO: 79. 
     Embodiment 16: The rAAV virion of any one of embodiments 1 to 15, wherein the expression cassette further comprises an intron. 
     Embodiment 17: The rAAV virion of embodiment 16, wherein the intron is selected from a CMV intron and a chimeric intron. 
     Embodiment 18: The rAAV virion of embodiment 17, wherein the CMV intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. 
     Embodiment 19: The rAAV virion of embodiment 17, wherein the CMV intron comprises SEQ ID NO: 80. 
     Embodiment 20: The rAAV virion of embodiment 17, wherein the chimeric intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81. 
     Embodiment 21: The rAAV virion of embodiment 17, wherein the chimeric intron comprises SEQ ID NO: 81. 
     Embodiment 22: The rAAV virion of any one of embodiments 1 to 21, wherein the expression cassette further comprises a WPRE sequence. 
     Embodiment 23: The rAAV virion of embodiment 22, wherein the WPRE sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 26. 
     Embodiment 24: The rAAV virion of embodiment 22, wherein the WPRE sequence comprises SEQ ID NO: 26. 
     Embodiment 25: The rAAV virion of any one of embodiments 1 to 24, wherein the expression cassette further comprises a polyadenylation sequence. 
     Embodiment 26: The rAAV virion of embodiment 25, wherein the polyadenylation sequence is selected from a BGH polyadenylation sequence and a SV40 polyadenylation sequence. 
     Embodiment 27: The rAAV virion of embodiment 26, wherein the BGH polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 27. 
     Embodiment 28: The rAAV virion of embodiment 26, wherein the BGH polyadenylation sequence comprises SEQ ID NO: 27. 
     Embodiment 29: The rAAV virion of embodiment 26, wherein the SV40 polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 28. 
     Embodiment 30: The rAAV virion of embodiment 26, wherein the SV40 polyadenylation sequence comprises SEQ ID NO: 28. 
     Embodiment 31: The rAAV virion of any one of embodiments 1 to 30, wherein the expression cassette is flanked by ITRs. 
     Embodiment 32: The rAAV virion of embodiment 31, wherein the ITRs share at least 90%, 95%, 96%, 97%, 98%, or 99% identity to one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     Embodiment 33: The rAAV virion of embodiment 31, wherein the ITRs comprise one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     Embodiment 34: The rAAV virion of any one of embodiments 1 to 33, wherein the expression cassette comprises a single promoter. 
     Embodiment 35: The rAAV virion of any one of embodiments 1 to 33, wherein the expression cassette comprises two promoters. 
     Embodiment 36: The rAAV virion of any one of embodiments 1 to 35, wherein the expression cassette comprises a single copy a sequence encoding the polypeptide. 
     Embodiment 37: The rAAV virion of any one of embodiments 1 to 35, wherein the expression cassette comprises two copies of a sequence encoding the polypeptide. 
     Embodiment 38: The rAAV virion of any one of embodiments 1 to 37, wherein the expression cassette comprises one, two, three, or four enhancers. 
     Embodiment 39: The rAAV virion of any one of embodiments 1 to 38, wherein the expression cassette comprises one or two introns. 
     Embodiment 40: The rAAV virion of any one of embodiments I to 39, wherein the expression cassette comprises one or two WPRE sequences. 
     Embodiment 41: The rAAV virion of any one of embodiments 1 to 40, wherein the expression cassette comprises one or two polyadenylation sequences. 
     Embodiment 42: The rAAV virion of any one of embodiments 1 to 41, wherein the expression cassette comprises about 3.2 kb, about, about 3.3 kb, about 3.4 kb, about 3.5 kb, about 3.6 kb, about 3.7 kb, or less. 
     Embodiment 43: The rAAV virion of any one of embodiments 1 to 42, wherein the expression cassette comprises about 1.9 kb, about 2.1 kb, about 2.2 kb, about 2.3 kb, about 2.4 kb, about 2.5 kb, about 2.6 kb, about 2.7 kb, about 2.8 kb, about 2.9 kb, about 3.0 kb, about 3.1 kb, about 3.2 kb, or more. 
     Embodiment 44: The rAAV virion of any one of embodiments 1-3, wherein the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a sequence within any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75 where the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 45: The rAAV virion of any one of embodiments 1-3, wherein the expression cassette comprises any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence within any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75 where the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 46: The rAAV virion of any one of embodiments 1-3, wherein the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59 and SEQ ID NO: 60, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence sharing at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59 and SEQ ID NO: 60 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 47: The rAAV virion of any one of embodiments 1-3, wherein the expression cassette comprises any one of SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59 and SEQ ID NO: 60, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence of SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59 and SEQ ID NO: 60 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 48: The rAAV virion of any one of embodiments 1-3, wherein the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%. 98%, or 99% identity to any one of SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence sharing at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 49: The rAAV virion of any one of embodiments 1-3, wherein the expression cassette comprises any one of SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence of any one of SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 50: The rAAV virion of any one of embodiments 1-3, wherein the expression cassette comprises a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 74, and SEQ ID NO: 75, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence sharing at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 74, and SEQ ID NO: 75 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 51: The rAAV virion of any one of embodiments 1-3, wherein the expression cassette comprises any one of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 74, and SEQ ID NO: 75, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence of any one of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 74, and SEQ ID NO: 75 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 52: The rAAV virion of any one of embodiments 1 to 51, wherein the capsid protein shares at least 98%, at least 99%, or 100% identity to an AAV9 capsid protein (SEQ ID NO: 143). 
     Embodiment 53: The rAAV virion of any one of embodiments 1 to 51, wherein the capsid protein shares at least 98%, at least 99%, or 100% identity to an AAV5 capsid protein (SEQ ID NO: 144). 
     Embodiment 54: The rAAV virion of any one of embodiments 1 to 51, wherein the capsid protein is a chimeric capsid protein. 
     Embodiment 55: The rAAV virion of any one of embodiments 1 to 51, wherein the capsid protein is an AAV5/AAV9 chimeric capsid protein. 
     Embodiment 56: The rAAV virion of any one of embodiments 1 to 51, wherein the capsid protein is selected from any one of SEQ ID NOs: 145-200. 
     Embodiment 57: An expression cassette comprising a polynucleotide sequence encoding a polypeptide operatively linked to a promoter, optionally wherein the polypeptide is for expression in a cardiac cell or tissue and/or for use in treating or a preventing a heart disease. 
     Embodiment 58: The expression cassette of embodiment 57, wherein the polypeptide is selected from DWORF, JPH2, BAG3, CRYAB, Lamin A isoform of LMNA, Lamin C isoform of LMNA, TNNI3, PLN, LAMP2a, LAMP2b, LAMP2c, DPI isoform of DSP, DPII isoform of DSP, DSG2, and JUP, optionally wherein the polypeptide shares at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to a sequence selected from polypeptide sequences in Tables 2a and 2b. 
     Embodiment 59: The expression cassette of embodiment 57 or 58, wherein the promoter is a chicken cTnT promoter. 
     Embodiment 60: The expression cassette of embodiment 59, wherein the chicken cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 11. 
     Embodiment 61: The expression cassette of embodiment 59, wherein the chicken cTnT promoter comprises SEQ ID NO: 11. 
     Embodiment 62: The expression cassette of embodiment 57 or 58, wherein the promoter is a human cTnT promoter. 
     Embodiment 63: The expression cassette of embodiment 62, wherein the human cTnT promoter shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 12 or SEQ ID NO: 13. 
     Embodiment 64: The expression cassette of embodiment 62, wherein the human cTnT promoter comprises SEQ ID NO: 12 or SEQ ID NO: 13. 
     Embodiment 65: The expression cassette of any one of embodiments 57 to 64, wherein the expression cassette further comprises one or more enhancers. 
     Embodiment 66: The expression cassette of embodiment 65, wherein the enhancer the one or more enhancers are selected from a ACTC1 cardiac enhancer and a αMHC enhancer. 
     Embodiment 67: The expression cassette of embodiment 66, wherein the ACTC1 cardiac enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 78. 
     Embodiment 68: The expression cassette of embodiment 66, wherein the ACTC1 cardiac enhancer comprises SEQ ID NO: 78. 
     Embodiment 69: The expression cassette of embodiment 66, wherein the αMHC enhancer shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 79. 
     Embodiment 70: The expression cassette of embodiment 66, wherein the αMHC enhancer comprises SEQ ID NO: 79. 
     Embodiment 71: The expression cassette of any one of embodiments 57 to 70, wherein the expression cassette further comprises an intron. 
     Embodiment 72: The expression cassette of any one of embodiments 57 to 70, wherein the intron is selected from a CMV intron and a chimeric intron. 
     Embodiment 73: The expression cassette of embodiment 72, wherein the CMV intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. 
     Embodiment 74: The expression cassette of embodiment 72, wherein the CMV intron comprises SEQ ID NO: 80. 
     Embodiment 75: The expression cassette of embodiment 72, wherein the chimeric intron shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81. 
     Embodiment 76: The expression cassette of embodiment 72, wherein the chimeric intron comprises SEQ ID NO: 81. 
     Embodiment 77: The expression cassette of any one of embodiments 57 to 76, wherein the expression cassette further comprises a WPRE sequence. 
     Embodiment 78: The expression cassette of embodiment 77, wherein the WPRE sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 26. 
     Embodiment 79: The expression cassette of embodiment 77, wherein the WPRE sequence comprises SEQ ID NO: 26. 
     Embodiment 80: The expression cassette of any one of embodiments 57 to 79, wherein the expression cassette further comprises a polyadenylation sequence. 
     Embodiment 81: The expression cassette of embodiment 80, wherein the polyadenylation sequence is selected from a BGH polyadenylation sequence and a SV40 polyadenylation sequence. 
     Embodiment 82: The expression cassette of embodiment 81, wherein the BGH polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 27. 
     Embodiment 83: The expression cassette of embodiment 81, wherein the BGH polyadenylation sequence comprises SEQ ID NO: 27. 
     Embodiment 84: The expression cassette of embodiment 81, wherein the SV40 polyadenylation sequence shares at least 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 28. 
     Embodiment 85: The expression cassette of embodiment 81, wherein the SV40 polyadenylation sequence comprises SEQ ID NO: 28. 
     Embodiment 86: The expression cassette of any one of embodiments 57 to 85, wherein the expression cassette is flanked by ITRs. 
     Embodiment 87: The expression cassette of embodiment 86, wherein the ITRs share at least 90%, 95%, 96%, 97%, 98%, or 99% identity to one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     Embodiment 88: The expression cassette of embodiment 86, wherein the ITRs comprise one or more of SEQ ID NO: 14 and SEQ ID NO: 15. 
     Embodiment 89: The expression cassette of any one of embodiments 57 to 88 comprising a single promoter. 
     Embodiment 90: The expression cassette of any one of embodiments 57 to 88 comprising two promoters. 
     Embodiment 91: The expression cassette of any one of embodiments 57 to 90 comprising a single copy a sequence encoding the polypeptide. 
     Embodiment 92: The expression cassette of any one of embodiments 57 to 90 comprising two copies of a sequence encoding the polypeptide. 
     Embodiment 93: The expression cassette of any one of embodiments 57 to 92 comprising one, two, three, or four enhancers. 
     Embodiment 94: The expression cassette of any one of embodiments 57 to 93 comprising one or two introns. 
     Embodiment 95: The expression cassette of any one of embodiments 57 to 94 comprising one or two WPRE sequences. 
     Embodiment 96: The expression cassette of any one of embodiments 57 to 95 comprising one or two polyadenylation sequences. 
     Embodiment 97: The expression cassette of any one of embodiments 57 to 96 comprising about 3.2 kb, about, about 3.3 kb, about 3.4 kb, about 3.5 kb, about 3.6 kb, about 3.7 kb, or less. 
     Embodiment 98: The expression cassette of any one of embodiments 57 to 97 comprising about 1.9 kb, about 2.1 kb, about 2.2 kb, about 2.3 kb, about 2.4 kb, about 2.5 kb, about 2.6 kb, about 2.7 kb, about 2.8 kb, about 2.9 kb, about 3.0 kb, about 3.1 kb, about 3.2 kb, or more. 
     Embodiment 99: The expression cassette of embodiment 57 or 58, comprising a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a sequence of any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 100: The expression cassette of embodiment 57 or 58, comprising a polynucleotide sequence of any one of SEQ ID NOs: 20-24 or SEQ ID NOs: 45-75, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises any one of SEQ NOs: 20-24 or SEQ ID NOs: 45-75 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 101: The expression cassette of embodiment 57 or 58, comprising a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, and SEQ ID NO: 60, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, and SEQ ID NO: 60 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 102: The expression cassette of embodiment 57 or 58, comprising a polynucleotide sequence of any one of SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, and SEQ ID NO: 60, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence of any one of SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, and SEQ ID NO: 60 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 103: The expression cassette of embodiment 57 or 58, comprising a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 104: The expression cassette of embodiment 57, comprising any one of SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence of any one of SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO: 58 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 105: The expression cassette of embodiment 57 or 58, comprising a polynucleotide sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 74, and SEQ ID NO: 75, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence that shares at least 75%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 74, and SEQ ID NO: 75 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 106: The expression cassette of embodiment 57 or 58, comprising any one of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 74, and SEQ ID NO: 75, optionally without the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF). In some embodiments, where the expression cassette is for expression of a polypeptide other than DWORF, the polynucleotide sequence comprises a sequence of any one of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 74, and SEQ ID NO: 75 in which the sequence or sequences encoding DWORF (open reading frame or open reading frames encoding DWORF) are replaced by a sequence or sequences encoding the polypeptide other than DWORF (e.g., any polypeptide described herein, such as any polypeptide listed in Table 2b which also provide sequences of such polypeptides). 
     Embodiment 107: The expression cassette of any one of embodiments 99 to 106, wherein the expression cassette does not comprise a 5′ inverted terminal repeat and a 3′ inverted. terminal repeat of the polynucleotide sequence. 
     Embodiment 108: A pharmaceutical composition comprising the rAAV virion of any one of embodiments 1 to 56 and a pharmaceutically acceptable carrier, or a pharmaceutical composition comprising a vector comprising the expression cassette of any of embodiments 57 to 107 and a pharmaceutically acceptable carrier. 
     Embodiment 109: A kit comprising the pharmaceutical composition of embodiment 108. 
     Embodiment 110: A method of increasing a polypeptide expression in a cell comprising contacting a cell with the rAAV virion of any one of embodiments 1 to 56, a vector comprising the expression cassette of any one of embodiments 57-107, or the composition of embodiment 108. 
     Embodiment 111: The method of embodiment 110, wherein the cell is a cardiac cell. 
     Embodiment 112: The method of embodiment 111, wherein the cardiac cell is a cardiomyocyte. 
     Embodiment 113: The method of any one of embodiments 110 to 112, wherein the polypeptide expression is increased between about 1.5-fold and 150-fold. 
     Embodiment 114: The method of any one of embodiments 110 to 113, wherein the contacting is in vitro. 
     Embodiment 115: The method of any one of embodiments 110 to 113, wherein the contacting is in vivo. 
     Embodiment 116: A method of increasing a polypeptide expression in a tissue comprising contacting the tissue with the rAAV virion of any one of embodiments 1 to 56, a vector comprising the expression cassette of any one of embodiments 57-107, or the composition of embodiment 108. 
     Embodiment 117: The method of embodiment 116, wherein the tissue is cardiac tissue. 
     Embodiment 118: The method of embodiment 116 or 117, wherein polypeptide expression is increased between about 1.5-fold and 150-fold. 
     Embodiment 119: The method of any one of embodiments 116 to 118, wherein the contacting is in vitro. 
     Embodiment 120: The method of embodiment 116 or 118, wherein the contacting is in vivo. 
     Embodiment 121: A method of increasing a polypeptide expression in an organ comprising contacting the organ with the rAAV virion of any one of embodiments 1 to 56, a vector comprising the expression cassette of any one of embodiments 57-107, or the composition of embodiment 108. 
     Embodiment 122: The method of embodiment 121, wherein the organ is a heart. 
     Embodiment 123: The method of embodiment 122, wherein the heart is diseased or is at risk of disease. 
     Embodiment 124: The method of embodiment 122 or embodiment 123, wherein the heart has reduced or borderline ejection fraction. 
     Embodiment 125: The method of embodiment 122 or embodiment 123, wherein the heart has a normal ejection fraction. 
     Embodiment 126: The method of any one of embodiments 122 to 125, wherein the heart comprises a genetic mutation associated with a heart disease. 
     Embodiment 127: The method of embodiment 126, wherein the genetic mutation is a PLN mutation. 
     Embodiment 128: The method of any one of embodiments 121 to 127, wherein the heart has low or undetectable polypeptide expression compared to a healthy heart. 
     Embodiment 129: The method of any one of embodiments 121 to 128, wherein the polypeptide expression is increased between about 1.5-fold and 150-fold. 
     Embodiment 130: The method of any one of embodiments 121 to 129, wherein the contacting is in vitro. 
     Embodiment 131: The method of any one of embodiments 121 to 129, wherein the contacting is in vivo. 
     Embodiment 132: A method of increasing a polypeptide expression in an subject comprising administering to the subject the rAAV virion of any one of embodiments 1 to 56, a vector comprising the expression cassette of any one of embodiments 57-107, or the composition of embodiment 108. 
     Embodiment 133: The method of embodiment 132, wherein the subject is an animal. 
     Embodiment 134: The method of embodiment 132, wherein the subject is a human. 
     Embodiment 135: The method of any one of embodiments 132 to 134, wherein the polypeptide expression is increased in the heart of the subject. 
     Embodiment 136: The method of any one of embodiments 132 to 135, wherein subject has a heart disease or is at risk of a heart disease. 
     Embodiment 137: The method of any one of embodiments 132 to 136, wherein subject has borderline or reduced ejection fraction. 
     Embodiment 138: The method of any one of embodiments 132 to 136, wherein the subject has normal ejection fraction. 
     Embodiment 139: The method of any one of embodiments 132 to 138, wherein the subject has a genetic mutation associated with a heart disease. 
     Embodiment 140: The method of embodiment 139, wherein the genetic mutation is a PLN mutation. 
     Embodiment 141: The method of any one of embodiments 132 to 140, wherein the subject has a low or undetectable level of the polypeptide expression compared to a healthy subject. 
     Embodiment 142: A method of treating a heart disease or disorder in a subject in need thereof comprising administering to the subject the rAAV virion of any one of embodiments 1 to 56, a vector comprising the expression cassette of any one of embodiments 57-107, or the composition of embodiment 108. 
     Embodiment 143: The method of embodiment 142, wherein the subject has a heart disease or disorder. 
     Embodiment 144: The method of embodiment 142, wherein the subject is a risk of developing a heart disease or disorder. 
     Embodiment 145: The method or any one of embodiments 142 to 144, wherein the heart disease or disorder is cardiomyopathy. 
     Embodiment 146: The method of any one of embodiments 142 to 144, wherein the heart disease or disorder is dilated cardiomyopathy. 
     Embodiment 147: The method of any one of embodiments 142 to 144, wherein the heart disease or disorder is myocardial infarction. 
     Embodiment 148: The method of any one of embodiments 142 to 144, wherein the heart disease or disorder is chronic myocardial infarction. 
     Embodiment 149: The method of any one of embodiments 142 to 144, wherein the heart disease or disorder is acute myocardial infarction. 
     Embodiment 150: The method of any one of embodiments 142 to 149, wherein the subject has an inherited risk allele for a heart disease or disorder. 
     Embodiment 151: The method of any one of embodiments 142 to 150, wherein the inherited risk allele comprises a mutation to the PLN gene. 
     Embodiment 152: The method of embodiment 151, wherein the mutation to the PLN gene is a PLN promoter mutation. 
     Embodiment 153: The method of embodiment 151, wherein the mutation to the PLN gene is a PLN L39stop  mutation. 
     Embodiment 154: The method of embodiment 151, wherein the mutation to the PLN gene is a RC9 mutation. 
     Embodiment 155: The method of embodiment 151, wherein the mutation to the PLN gene is a R9L mutation. 
     Embodiment 156: The method of embodiment 151, wherein the mutation to the PLN gene is a PLN gene duplication. 
     Embodiment 157: The method of embodiment 151, wherein the mutation to the PLN gene is a R14del mutation. 
     Embodiment 158: The method of any one of embodiments 142 to 157, wherein the heart disease or disorder is with reduced ejection fraction (HFrEF). 
     Embodiment 159: The method of any one of embodiments 142 to 157, wherein the heart disease of disorder is with preserved ejection fraction (HFpEF). 
     Embodiment 160: The method of any one of embodiments 142 to 159, wherein the method causes expression of the polypeptide in the heart of the subject. 
     Embodiment 161: The method of any one of embodiments 142 to 160, wherein the method causes expression of the polypeptide in cardiomyocytes. 
     Embodiment 162: The method of any one of embodiments 142 to 161, wherein the method causes no detectable expression of the polypeptide in the muscles of the subject except the heart. 
     Embodiment 163: The method of any one of embodiments 142 to 162, wherein the method causes no detectable expression of the polypeptide in the liver of the subject. 
     Embodiment 164: The method of any one of embodiments 142 to 163, wherein the method causes no detectable expression of the polypeptide in cardiac fibroblasts. 
     Embodiment 165: The method of any one of embodiments 142 to 164, wherein the method improves one or more measures of cardiac function, optionally fraction shortening and/or left ventricular internal dimension (LVID). 
     Embodiment 166: The method of any one of embodiments 142 to 165, wherein the improvement in cardiac function is observed at weeks 2 through week 24. 
     Embodiment 167: The method of any one of embodiments 142 to 166, herein the method reduces cardiac remodeling. 
     Embodiment 168: The method of any one of embodiments 142 to 166, wherein the method counteracts a decrease in the polypeptide expression in subjects suffering from or at risk of a heart disease. 
     Embodiment 169: The method of any one of embodiments 142 to 168, wherein the administering is by systemic administration. 
     Embodiment 170: The method of embodiment 169, wherein the systemic administration is selected from intravenous or intracoronary injection. 
     Embodiment 171: The method of embodiment 169 or 170, wherein the rAAV is administered as a unit dose. 
     Embodiment 172: The method of embodiment 171, wherein the unit dose comprises about 3×10 14  vg/kg or less, about 2×10 14  vg/kg or less, about 1×10 14  vg/kg or less, about 9×10 13  vg/kg or less, about 8×10 13  vg/kg or less, about 7×10 13  vg/kg or less, about 6×10 13  vg/kg or less, about 5×10 13  vg/kg or less, about 4×10 13  vg/kg or less, about 3×10 13  vg/kg or less, about 2×10 13  vg/kg or less, or about 1×10 13  vg/kg or less. 
     Embodiment 173: A method of alleviating one or more symptoms of a heart disease or disorder in a subject in need thereof comprising administering the rAAV virion of any one of embodiments 1 to 56, a vector comprising the expression cassette of any one of embodiments 57-107, or the composition of embodiment 108. 
     Embodiment 174: A method of improving one or more symptoms of a heart disease or disorder in a subject in need thereof comprising administering the rAAV virion of any one of embodiments 1 to 56, a vector comprising the expression cassette of any one of embodiments 57-107, or the composition of embodiment 108. 
     Embodiment 175: A method of preventing one or more symptoms of a heart disease or disorder in a subject in need thereof comprising administering the rAAV virion of any one of embodiments 1 to 56, a vector comprising the expression cassette of any one of embodiments 57-107, or the composition of embodiment 108. 
     Embodiment 176: An expression cassette comprising a polynucleotide comprising:
         i. one or more promoters;   ii. optionally one or more enhancers;   iii. optionally one or more introns;   iv. one or more transgenes, optionally wherein the one or more transgenes encode one or more polypeptides for use in treating or a preventing a heart disease;   v. optionally one or more WPRE sequences; and   vi. optionally one or more polyadenylation sequences, p(A).       

     Embodiment 177: The expression cassette of embodiment 176, wherein the 5′ to 3′ arrangement of elements is selected from:
     (i) 5′-promoter-transgene-WPRE-p(A)-3′;   (ii) 5′-promoter-intron-transgene-WPRE-p(A)-3′;   (iii) 5′-promoter-transgene-WPRE-p(A)-promoter-transgene-WPRE-p(A);   (iv) 5′-enhancer-promoter-transgene-WPRE-p(A)-3′;   (v) 5′-enhancer-promoter-intron-transgene-WPRE-p(A)-3′;   (vi) 5′-enhancer-enhancer-promoter-transgene-WPRE-p(A)-3′;   (vii) 5′-enhancer-enhancer-promoter-intron-transgene-WPRE-p(A)-3′;   (viii) 5′-enhancer-promoter-intron-transgene-WPRE-p(A)-p(A)-transgene-intron-promoter-enhancer-3′;   (ix) 5′-enhancer-promoter-intron-transgene-WPRE-p(A)-enhancer-promoter-intron-transgene-p(A)-3′;   (x) 5′-p(A)-WPRE-transgene-intron-promoter-enhancer-enhancer-promoter-intron-transgene-p(A)-3′;   (xi) 5′-promoter-intron-transgene-WPRE-p(A)-p(A)-transgene-intron-promoter-3′;   (xii) 5′-promoter-intron-transgene-WPRE-p(A)-promoter-intron-transgene-p(A)-3′; and   (xiii) 5′-p(A)-WPRE-transgene-intron-promoter-promoter-intron-transgene-p(A)-3′;   wherein optionally the transgene encodes a polypeptide for use in treating or a preventing a heart disease.   

     Embodiment 178: The expression cassette of embodiment 176 or embodiment 177, wherein the transgene has an increased expression level compared to a second expression cassette comprising a polynucleotide having an arrangement of elements from 5′ to 3′ comprising: 5′-promoter-transgene-WPRE-p(A)-3′. 
     Embodiment 179: The expression cassette of embodiment 178, wherein the increased expression level is between about 1.5-fold and about 150-fold compared to the second expression cassette. 
     Embodiment 180: A recombinant adeno-associated virus (rAAV) virion, comprising a capsid protein and a viral genome comprising an expression cassette of any one of embodiments 176 to 179, the expression cassette flanked by inverted terminal repeats. 
     Embodiment 181: The rAAV of embodiment 180, wherein the expression cassette comprises a transgene, wherein the transgene encodes a polypeptide for use in treating or a preventing a heart disease, or alleviating symptoms associated with a heart disease. 
     Embodiment 182: The rAAV of embodiment 180 or embodiment 181 wherein the capsid protein is selected from any one of SEQ ID NOs: 145-200. 
     EXAMPLES 
     Example 1: Novel Expression Cassettes 
     The purpose of this study was to evaluate several engineered expression cassettes for their ability to express a transgene in human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) and a mouse model. 
     The human DWORF (hDWORF) polynucleotide (SEQ ID NO: 33) was inserted into expression cassettes designed to induce strong cardiomyocyte-specific expression while maintaining a total size of 3-4.7 kbp in length. Three unique expression cassettes were generated, pCR-HD1 (SEQ ID NO: 22), pCR-HD2 (SEQ ID NO: 23), and pCR-HD3.  FIG.  1    shows an illustrative embodiment of each expression cassette, which contained iterations of a cardiac Troponin T promoter (see Table 3), WPRE (SEQ ID NO: 26) and BGH poly(A) signal (SEQ ID NO: 27). To evaluate expression of a transgene encoded by each expression cassette in hiPSC-CMs, the DWORF transgene was replaced with GFP in each expression cassettes, designated CR-G1, CR-G2, and CR-G3 corresponding to pCR-HD1, pCR-HD2, and pCR-HD3, respectively. The CR-G1, CR-G2, and CR-G3 expression cassettes were packaged into rAAV virions using an AAV6 capsid (SEQ ID NO: 39) protein. Cells were infected with each rAAV virion containing the expression cassette variants at an MOI of 50,000, and GFP expression was quantified by flow cytometry.  FIG.  2    shows the pCR-G1, pCR-G2, and pCR-G3 expression cassettes showed high levels of expression in hiPSC-CMs. Surprisingly, the double transgene construct exhibited lower expression, likely due to the homologous recombination between the tandem repeat sequences. Next, the expression cassettes containing hDWORF, pCR-HD1 and pCR-HD2 were evaluated in a wild type CD1 mouse model. Each cassette was packaged into rAAV virions using an AAV9 capsid protein. The rAAV virions (5×10 11  vg) were administered systemically by retro-orbital injection into wild type CD1 mice (N=2). Two weeks following injection, animals were sacrificed and hDWORF expression was assessed in hearts.  FIG.  3    shows the pCR-HD2 expression cassette results in about a 2-fold increase in hDWORF expression. It was concluded that increasing the length of the canonical hTNNT2 promoter from 600 bp to 1.5 kb, increasing total vector size from 1.9 kb to 3.2 kb, and/or inserting an intron surprisingly doubles gene expression. 
     Example 2: Evaluation in hiPSC-CMs 
     The purpose of this study was to evaluate the ability of chimeric capsid proteins to facilitate infection of hiPSC-CMs with an rAAV virion containing an expression cassette encoding an HA-tagged hDWORF protein and the chimeric capsid protein. 
     Expression cassettes encoding an HA-tagged hDWORF protein were packaged into rAAV virions with using a one of five chimeric capsid proteins. The chimeric capsid proteins tested include CR9-01 (SEQ ID NO: 29), CR9-10 (SEQ ID NO: 19), CR9-14 (SEQ ID NO: 30), TN44-07 (SEQ ID NO: 31), or TN47-10 (SEQ ID NO: 18), and the AAV9 capsid protein (SEQ ID NO: 16) was used as a control. Wild type hiPSC-CMs were infected at a MOI of 3,900. Five days following infection, cells were fixed and stained for SERCA2a and HA-tagged hDWORF. Stained cells were imaged ( FIG.  4 B ) and quantified ( FIG.  4 A ) using a cytation imager, and expression was normalized to AAV9.  FIG.  4 A  shows HA-tagged hDWORF expression in hiPSC-CM cell cultures infected with rAAV virions containing the CR9-01, CR9-10, CR9-14, or TN44-07 chimeric capsid proteins. Each of these capsids performed as well or better than the AAV9 capsid protein in delivering a. functional expression cassette. 
     Example 3: Evaluation in a Murine Model 
     The purpose of this study was to evaluate the ability of chimeric capsid proteins to facilitate infection of heart tissue in wildtype mice with an rAAV virion containing an expression cassette encoding an HA-tagged hDWORF protein and the chimeric capsid protein. 
     Expression cassettes encoding an HA-tagged hDWORF protein were packaged into rAAV virions with using one of five chimeric capsid proteins. The chimeric capsid proteins tested include CR9-01 (SEQ ID NO: 29), CR9-10 (SEQ ID NO: 19), CR9-14 (SEQ ID NO: 30), TN44-07 (SEQ ID NO: 31), or TN47-10 (SEQ ID NO: 18), and the AAV9 capsid protein (SEQ ID NO: 16) was used as a control. The rAAV virions were delivered by retro-orbital injection into wildtype mice at a dose of 5×10 11  vg/mouse (N=3). Fourteen days following injection, animals were sacrificed, and heart tissue was collected for RNA and protein analysis.  FIG.  5 A  shows hDWORF RNA expression in heart tissue infected with the indicated capsid. All expression levels were normalized to the expression levels in the AAV9 group. The results indicate that in vivo delivery of rAAV virions packaged with the CR9-01, CR9-10, CR9-14, TN44-07, and TN47-10 each showed increased hDWORF expression compared to parental AAV9. The rAAV virions containing the CR9-10 and TN47-10 capsids showed the highest levels of expression compared to the other tested capsids (˜9-fold and ˜11-fold increased, respectively).  FIG.  5 B  shows that hDWORF protein expression confirmed the RNA expression levels in the heart tissue, indicating that hDWORF RNA was translated to protein in the infected cells and that the modified capsids dramatically increased protein expression. 
     Example 4: DWORF Gene Therapy in a PLN-R14 Δ/Δ  Model 
     The purpose of this study was to evaluate the ability of rAAV virions containing an expression cassette encoding an mDWORF protein to reduce symptoms associated with cardiomyopathy in mice harboring the PLN-R14 deletion mutation. 
     Transgenic mice expressing a homozygous PLN gene harboring the arginine 14 deletion (PLN-R14 Δ/Δ ) recapitulates human cardiomyopathy, exhibiting similar histopathologic abnormalities and premature death (Haghighi K et al.  Proc. Natl. Acad. Sci. U.S.A  103:1388-1393 (2006)). In particular, the transgenic mice can be used as a model of dilated cardiomyopathy. The model is significantly more severe than a MLP −/−  knockout and clinically relevant, as there are no known MLP knockout cardiomyopathy patients. 
     In this study, three-week-old homozygous PLN-R14del animals were injected with either Hank&#39;s Balanced Salt Solution (HBSS) as sham control or rAAV virions comprised of the pCR-MD1 expression cassette (SEQ ID NO: 20) and the AAV9 capsid protein. PLN-R14 Δ/Δ  mice were administered rAAV virions by retro-orbital injection with a dose ranging from 5×10 12  vg/kg to 5×10 13  vg/kg (N=7-8/group). Ejection fraction and fractional shortening were assessed by echocardiography as markers of cardiac function at 6.5 weeks of age.  FIG.  6 A  show a dose-dependent improvement in ejection fraction compared to sham control (p=0.035).  FIG.  6 B  shows a dose-dependent improvement in fractional shortening compared to sham control (p=0.028). 
     Together these results indicate systemic administration of rAAV virions expressing DWORF improves cardiac function in an animal model of cardiomyopathy. Observation of this effect in mice treated at three weeks of age demonstrates that this gene therapy can both treat and prevent development of hypertrophic cardiomyopathy (HCM). 
     Example 5: rAAV-Mediated DWORF Expression 
     Expression cassettes were packaged with AAV9 capsid into rAAV virions and injected into 4 week old wildtype C57Bl6 mice at a dose of 5×10 13  vg/kg (N=4). Mouse hearts were harvested at 3 weeks following injection. DWORF protein expression was determined by Western blots and quantified ( FIG.  8 C , Table 10). A transgenic mouse (Tg-dworf) with a high DWORF expression level was used as a positive control. 
     The results show that combinations of specific promoters and enhancers and their orientation in the expression cassette lead to different levels of DWORF expression. The specific expression cassettes used in this example and the associated elements and their orientation are shown in  FIG.  7 A- 7 C . DWORF expression was increased with added elements compared to promoter alone, but the extent of increased DWORF expression was not predictable based on elements and orientation alone. 
       FIG.  8 A  shows the strategy for evaluating the expression of transgene (DWORF) in cardiomyocytes of naive mice. Three weeks post-injection, animals were sacrificed and DWORF expression was assessed in hearts.  FIG.  8 B  shows expression analysis results for 16 AAV constructs with various regulatory elements and arrangements to increase CM-selective expression of transgene (DWORF). In particular,  FIG.  8 B  shows the expression of DWORF in wild type C57BL6 mouse cardiomyocytes harvested three weeks after retro-orbital inject with AAV9:DWORF vectors as assessed by western blot; the lower western blot panels display the expression of GAPDH as a positive control. Quantification of these data in  FIG.  8 C  revealed that combinations of specific promoters and enhancers and their orientation in the expression cassette result in different levels of transgene expression. A transgenic mouse (Tg-dworf) with a high DWORF expression level was used as a positive control in this example. 
     For each expression cassette, DWORF expression was normalized to the observed level for the pCRmD1 expression cassette, which has only the human cTnT promoter without added enhancer elements. Adding the ACTC1 enhancer (pHZ15) or αMHC enhancer (pHZ17) increased DWORF expression about 3-fold to about 4-fold relative to pCRmD1. Adding the CMV intron (pHZ20) was observed to increase DWORF expression about 5-fold. Combining the promoter, a single enhancer, and an intron (pHZ22 and pHZ23) did not significantly increase DWORF expression compared to any element alone. Combining both enhancers with the promoter only marginally increased DWORF expression to about 6- to 8-fold compared to promoter alone. Surprising, the combination of both enhancers, a promoter, and an intron increased DWORF expression about 10- to 16-fold. Interestingly, the 5′ to 3′ order of enhancers plays a fine-tune role in regulating protein expression. Orienting the ACTC1 enhancer 5′ to the second enhancer (pHZ16 or pHZ21) appears to increase DWORF expression compared to orienting the ACTC1 enhancer 3′ to the second enhancer (pHZ18 or pHZ19). Including a codon optimized DWORF transgene (pHZ24) also increased expression. 
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 DWORF Expression 
               
            
           
           
               
               
               
            
               
                   
                   
                 DWORF Expression  
               
               
                   
                 Expression 
                 Fold Increase over 
               
               
                   
                 Cassette 
                 Promoter Only 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 pCRmD1 
                 1.0 
               
               
                   
                 pHZ15 
                 3.9 
               
               
                   
                 pHZ16 
                 8.2 
               
               
                   
                 pHZ17 
                 3.3 
               
               
                   
                 pHZ18 
                 6.0 
               
               
                   
                 pHZ19 
                 10.0 
               
               
                   
                 pHZ20 
                 4.8 
               
               
                   
                 pHZ21 
                 16.6 
               
               
                   
                 pHZ22 
                 5.0 
               
               
                   
                 pHZ23 
                 6.5 
               
               
                   
                 pHZ24 
                 8.2 
               
               
                   
                 pHZ25 
                 108.0 
               
               
                   
                 pHZ33 
                 94.2 
               
               
                   
                 pHZ34 
                 112.6 
               
               
                   
                 pHZ69 
                 139.3 
               
               
                   
                 pHZ72 
                 41.2 
               
               
                   
                 pHZ75 
                 60.6 
               
               
                   
                 Tg-DWORF 
                 113.7 
               
               
                   
                 (Positive  
                   
               
               
                   
                 Control) 
               
               
                   
                   
               
            
           
         
       
     
     Although adding various regulatory elements greatly increased DWORF expression, adding more copies of the transgene (pHZ25, pHZ33, pHZ34, pHZ69, pHZ72 and pHZ75) has an unexpected synergistic impact on DWORF levels. We used different enhancers, promoters, introns, and codon-optimized DWORF in each copy to avoid the homologous recombination between the tandem repeat sequences. The dual copies vectors have about 40- to 140-fold more expression than DWORF under transcriptional control of the promoter alone. Surprisingly, the orientation of the two copies has an unexpected role in regulating gene expression. For example, a tail-to-tail orientation shows the best expression, followed by head-to-head and head-to-tail arrangements. The results also suggest that different arrangements of the two copies of the transgene can be used to fine-tune the transgene expression. 
     Example 6: Effect of DWORF Expression on Ejection Fraction 
     The effect of rAAV mediated DWORF expression on ejection fraction was determined in an MLP knockout (MLP-KO) dilated cardiomyopathy (DCM) model. Three of the rAAV virions were tested, including those with vector genomes having a single copy expression cassettes pHZ19 and pHZ21, and one having a dual copy expression cassette pHZ34. MLP-KO mice were dosed with either pHZ19 at 5×10 13  vg/kg, pHZ21 at 5×10 13  vg/kg, or pHZ34 at 1×10 13  vg/kg. Virions were delivered by retro-orbital injection at 6 weeks of age, at which time the mice were presenting with moderate heart failure. Cardiac functions were accessed by echocardiography at 3, 6, 9, 12, 16 and 20 weeks post-treatment. As shown in  FIG.  9   , pHZ21 at a 5×10 13  vg/kg dose significantly improved ejection fraction (14.4%) by 16 weeks post-virus injection compared to the HBSS group. Although pHZ21 only has a 1.6 fold more DWORF expression than the pHZ19, this modest improvement in expression seems to have a very profound effect on improving cardiac function. The dose of pHZ34 is five times lower than the pHZ19 and pHZ21, but it achieved similar improvement as the pHZ21 and better improvement than pHZ19, highlight the importance of DWORF expression. 
     Three of the DWORF expression cassettes were tested in another well characterized DCM model, the BAG3 cardiac conditional knock-out (BAG3-cKO) model. DWORF expression cassettes were tested in this model included one single copy vector, the pHZ21, and two dual-copy vectors, pHZ72 and pHZ75. BAG3-cKO mice were dosed with either 5×10 13  vg/kg AAV9-pHZ21, AAV9-pHZ72 and AAV9-pHZ75. Virions were delivered by retro-orbital injection at 8 weeks of age when the mice have already developed moderate heart failure. Cardiac functions were accessed by echocardiography at 3 and 6 weeks post-treatment. As shown in  FIG.  10   , pHZ72 at a 5×10 13  vg/kg dose substantially improved ejection fraction (7.4%) by 6 weeks post-virus injection compared to the HBSS group, suggesting that such optimized DWORF gene therapy can improve cardiac function in this model. 
     Example 7: Effect of DWORF Constructs in a Severe MLP-KO DCM Mouse Model 
     The purpose of this study was to test how optimized DWORF vectors can improve heart function and exercise capacity in a well-characterized MLP knockout (MLP-KO) dilated cardiomyopathy model. 
       FIG.  11 A  is the schematic diagram of the study design. Three of the rAAV virions were tested, including those with vector genomes having a single copy expression cassettes pHZ19 and pHZ21, and one having a dual copy expression cassette pHZ34. MLP-KO mice were dosed with either pHZ19 at 5×10 13  vg/kg, pHZ21 at 5×10 13  vg/kg, or pHZ34 at 1×10 13  vg/kg. Virions were delivered by retro-orbital injection at 6 weeks of age, at which time the mice were presenting with moderate heart failure. Cardiac functions were accessed by echocardiography 3-4 weeks and up to 24 weeks post-treatment. MLP-KI mice have limited exercise capacity compared to their wild-type littermates. To assess how much DWORF gene therapy can improve exercise capacity in MLP-KO mice, mice were allowed to run on a rodent treadmill and their running duration was monitored at 26 weeks. 
     As shown in  FIG.  11 B  and  FIG.  11 C , pHZ21 at a 5×10 13  vg/kg dose significantly improved ejection fraction (14.3%) by 24 weeks post-virus injection compared to the HBSS group. Although pHZ21 only has a 1.6 fold more DWORF expression than the pHZ19, this modest improvement in expression seems to have a very profound effect on improving cardiac function. The dose of pHZ34 is five times lower than the pHZ19 and pHZ21, but it achieved similar improvement as the pHZ21 and better improvement than pHZ19, highlighting the importance of DWORF expression.  FIG.  11 D  and  FIG.  11 E  show that MLP-KO mice have limited exercise capacity compared to their wild-type littermates. pHZ21, the best DWORF vector to improve ejection fraction, also significantly improved exercise capacity, including running distance and time to exhaustion, in the MLP KO DCM mouse model 26 weeks post-treatment relative to the saline control. 
     Overall, this study shows that AAV-delivered DWORF mitigated the contractile dysfunction and improved exercise capacity in this MLP-KO DCM model. AAV:DWORF cassettes expressed higher levels of DWORF, supporting the most significant degree of efficacy that was durable out to 24 weeks. These results show that DWORF gene therapy can he used for normalizing calcium homeostasis and limiting disease progression. 
     Example 8: Tolerability of DWORF Gene Therapy in NaïMice 
     The purpose of this study was to evaluate the tolerability of DWORF gene therapy in naïve mice.  FIG.  12 A  is the schematic diagram of the study design. Naïve mice were dosed with either HBSS saline control or AAV9:pHZ21 vector at two doses: 5×10 13  vg/kg and 2×10 14  vg/kg. Viruses were delivered via intraperitoneal (IP) injection at postnatal day 3 (P3). Cardiac functions were evaluated by echocardiography 4 weeks after viral injection. 
       FIG.  12 B  shows that AAV9:pHZ21 is well tolerated in wild-type mice up to 2×10 14  vg/kg. Compared with the saline control group, there are no differences in body weight, ejection fraction, heart rate, and left ventricular mass (LV mass) for those groups that were dosed with AAV9:pHZ21. 
     Incorporation by Reference 
     Various references such as patents, patent applications, and publications are cited herein, the disclosures of which are hereby incorporated herein by reference in their entireties. Also, all references mentioned herein are specifically incorporated by reference to disclose and describe the methods and/or materials in connection with which the publications are cited.