Patent Publication Number: US-2021188927-A1

Title: Compositions and methods for treating age-related macular degeneration

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/574,814, filed Oct. 20, 2017. The disclosure of the foregoing application is hereby incorporated by reference in its entirety. 
    
    
     BACKGROUND OF THE DISCLOSURE 
     Age-related macular degeneration (AMD) is a medical condition and is the leading cause of legal blindness in Western societies. AMD typically affects older adults and results in a loss of central vision due to degenerative and neovascular changes to the macula, a pigmented region at the center of the retina which is responsible for visual acuity. There are four major AMD subtypes: Early AMD; Intermediate AMD; Advanced non-neovascular (“Dry”) AMD; and Advanced neovascular (“Wet”) AMD. Typically, AMD is identified by the focal hyperpigmentation of the retinal pigment epithelium (RPE) and accumulation of drusen deposits. The size and number of drusen deposits typically correlates with AMD severity. AMD occurs in up to 8% of individuals over the age of 60, and the prevalence of AMD continues to increase with age. The U.S. is anticipated to have nearly 22 million cases of AMD by the year 2050, while global cases of AMD are expected to be nearly 288 million by the year 2040. 
     There is a need for novel treatments for preventing progression from early to intermediate and/or from intermediate to advanced stages of AMD to prevent loss of vision. 
     SUMMARY OF THE DISCLOSURE 
     In some embodiments, the disclosure provides for an adeno-associated viral (AAV) vector encoding a Complement Factor H (CFH) or human Factor H Like 1 (FHL1) protein or biologically active fragment thereof, wherein the vector comprises a nucleotide sequence that is at least 80% identical to the nucleotide sequence of SEQ ID NO: 1-3 or 5, or a fragment thereof. In some embodiments, the nucleotide sequence is at least 90% identical to the nucleotide sequence of SEQ ID NO: 1-3 or 5, or codon-optimized variant and/or a fragment thereof. In some embodiments, the nucleotide sequence is at least 95% identical to the nucleotide sequence of SEQ ID NO: 1-3 or 5, or codon-optimized variant and/or a fragment thereof. In some embodiments, the nucleotide sequence is the sequence of SEQ ID NO: 1-3 or 5, or codon-optimized variant and/or a fragment thereof. In some embodiments, the vector encodes a CFH protein or biologically active fragment thereof comprising at least four CCP domains. In some embodiments, the vector encodes a CFH protein or biologically active fragment thereof comprising at least five CCP domains. In some embodiments, the vector encodes a CFH protein or biologically active fragment thereof comprising at least six CCP domains. In some embodiments, the vector encodes a CFH protein or biologically active fragment thereof comprising at least seven CCP domains. In some embodiments, the vector encodes a CFH protein or biologically active fragment thereof comprising at least three CCP domains. In some embodiments, the vector encodes a CFH protein or biologically active fragment thereof comprising the H402 polymorphism. In some embodiments, the vector encodes a CFH protein or biologically active fragment thereof comprising the V62 polymorphism. In some embodiments, the CFH protein or biologically active fragment thereof comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the amino acid sequence of SEQ ID NO: 4 is the C-terminal sequence of the CFH protein. In some embodiments, the CFH protein or biologically active fragment thereof is capable of diffusing across the Bruch&#39;s membrane. In some embodiments, the CFH protein or biologically active fragment thereof is capable of binding C3b. In some embodiments, the CFH protein or biologically active fragment thereof is capable of facilitating the breakdown of C3b. In some embodiments, the vector comprises a promoter that is less than 1000 nucleotides in length. In some embodiments, the vector comprises a promoter that is less than 500 nucleotides in length. In some embodiments, the vector comprises a promoter that is less than 400 nucleotides in length. In some embodiments, the promoter comprises a promoter having the nucleotide sequence of SEQ ID NO: 6, or a fragment thereof. In some embodiments, the promoter comprises a promoter having the nucleotide sequence of SEQ ID NO: 8, or a fragment thereof. In some embodiments, the promoter comprises a promoter having the nucleotide sequence of SEQ ID NO: 12, or a fragment thereof. In some embodiments, the promoter comprises a promoter having the nucleotide sequence of SEQ ID NO: 14, or a fragment thereof. In some embodiments, the promoter comprises a promoter having the nucleotide sequence of SEQ ID NO: 16, or a fragment thereof. In some embodiments, the promoter comprises a promoter having the nucleotide sequence of SEQ ID NO: 18, or a fragment thereof. In some embodiments, the promoter comprises a promoter having the nucleotide sequence of SEQ ID NO: 20, or a fragment thereof. In some embodiments, the promoter comprises a promoter having the nucleotide sequence of SEQ ID NO: 31, or a fragment thereof. In some embodiments, the promoter comprises a promoter having the nucleotide sequence of SEQ ID NO: 32, or a fragment thereof. In some embodiments, the promoter comprises a promoter having a nucleotide sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 92%, 93%, 95%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 6, or a biologically active fragment thereof. In some embodiments, the promoter comprises a promoter having a nucleotide sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 92%, 93%, 95%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 8, or a biologically active fragment thereof. In some embodiments, the promoter comprises a promoter having a nucleotide sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 92%, 93%, 95%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 12, or a biologically active fragment thereof. In some embodiments, the promoter comprises a promoter having a nucleotide sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 92%, 93%, 95%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 14, or a biologically active fragment thereof. In some embodiments, the promoter comprises a promoter having a nucleotide sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 92%, 93%, 95%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 16, or a biologically active fragment thereof. In some embodiments, the promoter comprises a promoter having a nucleotide sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 92%, 93%, 95%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 18, or a biologically active fragment thereof. In some embodiments, the promoter comprises a promoter having a nucleotide sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 92%, 93%, 95%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 20, or a biologically active fragment thereof. In some embodiments, the promoter comprises a promoter having a nucleotide sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 92%, 93%, 95%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 31, or a biologically active fragment thereof. In some embodiments, the promoter comprises a promoter having a nucleotide sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 92%, 93%, 95%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 32, or a biologically active fragment thereof. In some embodiments, the promoter comprises a promoter having a nucleotide sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 92%, 93%, 95%, 98%, or 99% identical to the nucleotide sequence of SEQ ID NO: 32, or a biologically active fragment thereof. In some embodiments, the promoter comprises an additional viral intron. In some embodiments, the additional viral intron comprises the nucleotide sequence of SEQ ID NO: 10, or a fragment thereof. In some embodiments, the vector is an AAV2 vector. In some embodiments, the vector comprises a CMV promoter. In some embodiments, the vector comprises a Kozak sequence. In some embodiments, the vector comprises one or more ITR sequence flanking the vector portion encoding CFH. In some embodiments, the vector comprises a polyadenylation sequence. In some embodiments, the vector comprises a selective marker. In some embodiments, the selective marker is an antibiotic-resistance gene. In some embodiments, the antibiotic-resistance gene is an ampicillin-resistance gene. 
     In some embodiments, the disclosure provides a composition comprising any of the vectors disclosed herein and a pharmaceutically acceptable carrier. 
     In some embodiments, the disclosure provides for a method of treating a subject having a disorder associated with undesired activity of the alternative complement pathway, comprising the step of administering to the subject any of the vectors disclosed herein or any of the compositions disclosed herein. 
     In some embodiments, the disclosure the provides for a method of treating a subject having age-related macular degeneration (AMD), comprising the step of administering to the subject any of the vectors disclosed herein or any of the compositions disclosed herein. In some embodiments, the the vector or composition is administered intravitreally. In some embodiments, the subject is not administered a protease or a polynucleotide encoding a protease. In some embodiments, the subject is not administered a furin protease or a polynucleotide encoding a furin protease. In some embodiments, the subject is a human. In some embodiments, the human is at least 40 years of age. In some embodiments, the human is at least 50 years of age. In some embodiments, the human is at least 65 years of age. In some embodiments, the vector or composition is administered locally. In some embodiments, the vector or composition is administered systemically. In some embodiments, the vector or composition comprises a promoter that is associated with strong expression in the liver. In some embodiments, the promoter comprises a nucleotide sequence that is at least 90%, 95% or 100% identical to the nucleotide sequence of any one of SEQ ID NOs: 16, 18, or 20. In some embodiments, the vector or composition comprises a promoter that is associated with strong expression in the eye. In some embodiments, the promoter comprises a nucleotide sequence that is at least 90%, 95%, or 100% identical to the nucleotide sequence of any one of SEQ ID NOs: 6 or 32. In some embodiments, the subject has a loss-of-function mutation in the subject&#39;s CFI gene. In some embodiments, the subject has one or more CFI mutations selected from the group consisting of: G119R, L131R, V152M, G162D, R187Y, R187T, T2031, A240G, A258T, G287R, A300T, R317W, R339Q, V412M, and P553S. In some embodiments, the subject has a loss-of-function mutation in the subject&#39;s CFH gene. In some embodiments, the subject has one or more CFH mutations selected from the group consisting of: R2T, L3V, R53C, R53H, S58A, G69E, D90G, R175Q, S193L, I216T, I221V, R303W, H402Y, Q408X, P503A, G650V, R1078S, and R1210C. In some embodiments, the subject has atypical hemolytic uremic syndrome (aHUS). In some embodiments, the subject is suffering from a renal disease or complication. In some embodiments, any of the vectors disclosed herein or any of the compositions disclosed herein is capable of inducing at least 20%, 50%, 100%, 150%, 200%, 250%, 300%, 400%, 500%, 700%, 900%, 1000%, 1100%, 1500%, or 2000% higher expression of CFH or FHL in a target cell (e.g., an RPE or liver cell) as compared to the endogenous expression of CFH or FHL in the target cell. In some embodiments, the expression of any of the vectors disclosed herein or any of the compositions disclosed herein (e.g., an RPE or liver cell) results in at least 20%, 50%, 100%, 150%, 200%, 250%, 300%, 400%, 500%, 700%, 900%, 1000%, 1100%, 1500%, or 2000% higher levels of CFH or FHL activity in the target cell as compared to endogenous levels of CFH or FHL activity in the target cell. In some embodiments, any of the vectors disclosed herein or any of the compositions disclosed herein induces CFH expression in a target cell of the eye. In some embodiments, any of the vectors or compositions disclosed herein induces CFH expression in a target cell of the retina or macula. In some embodiments, target cell of the retina is selected from the group of layers consisting of: inner limiting membrane, nerve fiber, ganglion cell layer (GCL), inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, external limiting membrane, rods and cones, and retinal pigment epithelium (RPE). In some embodiments, the target cell is in the choroid plexus. In some embodiments, the target cell is in the macula. In some embodiments, any of the vectors or compositions disclosed herein induces CFH expression in a cell of the GCL and/or RPE. In some embodiments, the vector or composition is administered to the retina at a dose in the range of 1×10 10  vg/eye to 1×10 13  vg/eye. In some embodiments, the vector or composition is administered to the retina at a dose of about 1.4×10 12  vg/eye. In some embodiments, the promoter comprises a promoter having the nucleotide sequence of SEQ ID NO: 36, or a fragment thereof. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows a vector map of a full vector genome construct for expression of CFH. “ITR” corresponds to inverted terminal repeats; “CRALBP promoter” corresponds to the cellular retinaldehyde-binding protein promoter; “CFH” corresponds to the gene encoding Complement Factor H; “polyA” corresponds to the polyadenylation sequence; “Amp R” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 1  is SEQ ID NO: 7. 
         FIG. 2  shows a vector map of a full vector genome construct for expression of CFH. “ITR” corresponds to inverted terminal repeats; “EF1a promoter” corresponds to the elongation factor-1 alpha promoter; “CFH” corresponds to the gene encoding Complement Factor H; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 2  is SEQ ID NO: 9. 
         FIG. 3  shows a vector map of a full vector genome construct for expression of CFH. “ITR” corresponds to inverted terminal repeats; “EF1a.SV40i” corresponds to the elongation factor-1 alpha promoter including the simian virus 40 intron; “CFH” corresponds to the gene encoding Complement Factor H; “polyA” corresponds to the polyadenylation sequence; “AmpicillinR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 3  is SEQ ID NO: 11. 
         FIG. 4  shows a vector map of a full vector genome construct for expression of CFH. “ITR” corresponds to inverted terminal repeats; “HSP70 promoter” corresponds to the heat shock protein 70 promoter; “CFH” corresponds to the gene encoding Complement Factor H; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 4  is SEQ ID NO: 13. 
         FIG. 5  shows a vector map of a full vector genome construct for expression of CFH. “ITR” corresponds to inverted terminal repeats; “sCBA promoter” corresponds to the chicken 13 actin promoter; “CFH” corresponds to the gene encoding Complement Factor H; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. This vector also included the SV40i intron. The nucleotide sequence corresponding to the vector illustrated in  FIG. 5  is SEQ ID NO: 15. 
         FIG. 6  shows a vector map of a full vector genome construct for expression of CFH. “ITR” corresponds to inverted terminal repeats; “AAT1” corresponds to the alpha-1 antitrypsin 1 promoter; “CFH” corresponds to the gene encoding Complement Factor H; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 6  is SEQ ID NO: 17. 
         FIG. 7  shows a vector map of a full vector genome construct for expression of CFH. “ITR” corresponds to inverted terminal repeats; “ALB” corresponds to a synthetic promoter based on the human albumin promoter; “CFH” corresponds to the gene encoding Complement Factor H; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 7  is SEQ ID NO: 19. 
         FIG. 8  shows a vector map of a full vector genome construct for expression of CFH. “ITR” corresponds to inverted terminal repeats; “PCK1” corresponds to the phosphoenolpyruvate carboxykinase 1 promoter; “CFH” corresponds to the gene encoding Complement Factor H; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 8  is SEQ ID NO: 21. 
         FIG. 9  shows a vector map of a full vector genome construct for expression of FHL-1. “ITR” corresponds to inverted terminal repeats; “EF1a” corresponds to the elongation factor-1 alpha promoter; “FHL-1” corresponds to the gene encoding Factor-H-Like Protein 1; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 9  is SEQ ID NO: 22. 
         FIG. 10  shows a vector map of a full vector genome construct for expression of FHL-1. “ITR” corresponds to inverted terminal repeats; “ALB” corresponds to a synthetic promoter based on the human albumin promoter; “FHL-1” corresponds to the gene encoding Factor-H-Like Protein 1; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 10  is SEQ ID NO: 23. 
         FIG. 11  shows a vector map of a full vector genome construct for expression of FHL-1. “ITR” corresponds to inverted terminal repeats; “AAT1” corresponds to the alpha-1 antitrypsin 1 promoter; “FHL-1” corresponds to the gene encoding Factor-H-Like Protein 1; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 11  is SEQ ID NO: 24. 
         FIG. 12  shows a vector map of a full vector genome construct for expression of FHL-1. “ITR” corresponds to inverted terminal repeats; “EF1a.SV40i” corresponds to the elongation factor-1 alpha promoter including the simian virus 40 intron; “FHL-1” corresponds to the gene encoding Factor-H-Like Protein 1; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 12  is SEQ ID NO: 25. 
         FIG. 13  shows a vector map of a full vector genome construct for expression of FHL-1. “ITR” corresponds to inverted terminal repeats; “CAG” corresponds to a synthetic promoter that includes the cytomegalovirus (CMV) early enhancer element, the promoter/first exon/first intron of chicken beta-actin gene, and the splice acceptor of the rabbit beta-globin gene; “FHL-1” corresponds to the gene encoding Factor-H-Like Protein 1; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 13  is SEQ ID NO: 26. 
         FIG. 14  shows a vector map of a full vector genome construct for expression of FHL-1. “ITR” corresponds to inverted terminal repeats; “CRALBP” corresponds to the cellular retinaldehyde-binding protein promoter; “FHL-1” corresponds to the gene encoding Factor-H-Like Protein 1; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 14  is SEQ ID NO: 27. 
         FIG. 15  shows a vector map of a full vector genome construct for expression of FHL-1. “ITR” corresponds to inverted terminal repeats; “hRPE65” corresponds to the retinal pigment epithelial 65 promoter; “FHL-1” corresponds to the gene encoding Factor-H-Like Protein 1; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 15  is SEQ ID NO: 28. 
         FIG. 16  shows a vector map of a full vector genome construct for expression of FHL-1. “ITR” corresponds to inverted terminal repeats; “HSP70” corresponds to the heat shock protein 70 promoter; “FHL-1” corresponds to the gene encoding Factor-H-Like Protein 1; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 16  is SEQ ID NO: 29. 
         FIG. 17  shows a vector map of a full vector genome construct for expression of FHL-1. “ITR” corresponds to inverted terminal repeats; “PCK1” corresponds to the phosphoenolpyruvate carboxykinase 1 promoter; “FHL-1” corresponds to the gene encoding Factor-H-Like Protein 1; “polyA” corresponds to the polyadenylation sequence; “AmpR” corresponds to the ampicillin resistance cassette. The nucleotide sequence corresponding to the vector illustrated in  FIG. 17  is SEQ ID NO: 30. 
         FIG. 18  shows a Western Blot from an experiment in which the levels of CFH (or the loading control GAPDH) were detected in HEK cells transfected with various CFH or control plasmids. 
         FIG. 19  shows a bar graph comparing the levels of CFH protein levels from the Western analysis of  FIG. 18  relative to GAPDH protein levels. 
         FIG. 20  shows a Western Blot from an experiment in which the levels of CFH or GFP (or the loading control GAPDH) were detected in HEK cells transfected with various CFH or control AAV vectors. 
     
    
    
     DETAILED DESCRIPTION OF THE DISCLOSURE 
     The disclosure provides compositions and methods for treating, preventing, or inhibiting diseases of the eye. In one aspect, the disclosure provides recombinant adeno-associated virus (rAAV) vectors comprising a complement system gene (such as, but not limited to genes encoding complement factor H (CFH) or factor-H-like protein 1 (FHL1)). In another aspect, the disclosure provides methods of treating, preventing, or inhibiting diseases of the eye by intraocularly (e.g., intravitreally) administering an effective amount of an rAAV vector of the disclosure to deliver and drive the expression of a complement factor gene. 
     A wide variety of diseases of the eye may be treated or prevented using the viral vectors and methods provided herein. Diseases of the eye that may be treated or prevented using the vectors and methods of the disclosure include but are not limited to, glaucoma, macular degeneration (e.g., age-related macular degeneration), diabetic retinopathies, inherited retinal degeneration such as retinitis pigmentosa, retinal detachment or injury and retinopathies (such as retinopathies that are inherited, induced by surgery, trauma, an underlying aetiology such as severe anemia, SLE, hypertension, blood dyscrasias, systemic infections, or underlying carotid disease, a toxic compound or agent, or photically). 
     GENERAL TECHNIQUES 
     Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings that are commonly understood by those of ordinary skill in the art. Generally, nomenclature used in connection with, and techniques of, pharmacology, cell and tissue culture, molecular biology, cell and cancer biology, neurobiology, neurochemistry, virology, immunology, microbiology, genetics and protein and nucleic acid chemistry, described herein, are those well known and commonly used in the art. In case of conflict, the present specification, including definitions, will control. 
     The practice of the present disclosure will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry and immunology, which are within the skill of the art. Such techniques are explained fully in the literature, such as, Molecular Cloning: A Laboratory Manual, second edition (Sambrook et al., 1989) Cold Spring Harbor Press; Oligonucleotide Synthesis (M. J. Gait, ed., 1984); Methods in Molecular Biology, Humana Press; Cell Biology: A Laboratory Notebook (J. E. Cellis, ed., 1998) Academic Press; Animal Cell Culture (R. I. Freshney, ed., 1987); Introduction to Cell and Tissue Culture (J. P. Mather and P. E. Roberts, 1998) Plenum Press; Cell and Tissue Culture: Laboratory Procedures (A. Doyle, J. B. Griffiths, and D. G. Newell, eds., 1993-1998) J. Wiley and Sons; Methods in Enzymology (Academic Press, Inc.); Gene Transfer Vectors for Mammalian Cells (J. M. Miller and M. P. Calos, eds., 1987); Current Protocols in Molecular Biology (F. M. Ausubel et al., eds., 1987); PCR: The Polymerase Chain Reaction, (Mullis et al., eds., 1994); Sambrook and Russell, Molecular Cloning: A Laboratory Manual, 3rd. ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (2001); Ausubel et al., Current Protocols in Molecular Biology, John Wiley &amp; Sons, N Y (2002); Harlow and Lane Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1998); Coligan et al., Short Protocols in Protein Science, John Wiley &amp; Sons, N Y (2003); Short Protocols in Molecular Biology (Wiley and Sons, 1999). 
     Enzymatic reactions and purification techniques are performed according to manufacturer&#39;s specifications, as commonly accomplished in the art or as described herein. The nomenclatures used in connection with, and the laboratory procedures and techniques of, analytical chemistry, biochemistry, immunology, molecular biology, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well known and commonly used in the art. Standard techniques are used for chemical syntheses, and chemical analyses. 
     Throughout this specification and embodiments, the word “comprise,” or variations such as “comprises” or “comprising,” will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers. 
     It is understood that wherever embodiments are described herein with the language “comprising,” otherwise analogous embodiments described in terms of “consisting of” and/or “consisting essentially of” are also provided. 
     The term “including” is used to mean “including but not limited to.” “Including” and “including but not limited to” are used interchangeably. 
     Any example(s) following the term “e.g.” or “for example” is not meant to be exhaustive or limiting. 
     Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. 
     The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. Reference to “about” a value or parameter herein includes (and describes) embodiments that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X.” Numeric ranges are inclusive of the numbers defining the range. 
     Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Moreover, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a stated range of “1 to 10” should be considered to include any and all subranges between (and inclusive of) the minimum value of 1 and the maximum value of 10; that is, all subranges beginning with a minimum value of 1 or more, e.g., 1 to 6.1, and ending with a maximum value of 10 or less, e.g., 5.5 to 10. 
     Where aspects or embodiments of the disclosure are described in terms of a Markush group or other grouping of alternatives, the present disclosure encompasses not only the entire group listed as a whole, but each member of the group individually and all possible subgroups of the main group, but also the main group absent one or more of the group members. The present disclosure also envisages the explicit exclusion of one or more of any of the group members in the embodimented disclosure. 
     Exemplary methods and materials are described herein, although methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure. The materials, methods, and examples are illustrative only and not intended to be limiting. 
     Definitions 
     The following terms, unless otherwise indicated, shall be understood to have the following meanings: 
     As used herein, “residue” refers to a position in a protein and its associated amino acid identity. 
     As known in the art, “polynucleotide,” or “nucleic acid,” as used interchangeably herein, refer to chains of nucleotides of any length, and include DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and/or their analogs, or any substrate that can be incorporated into a chain by DNA or RNA polymerase. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and their analogs. If present, modification to the nucleotide structure may be imparted before or after assembly of the chain. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component. Other types of modifications include, for example, “caps”, substitution of one or more of the naturally occurring nucleotides with an analog, internucleotide modifications such as, for example, those with uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoamidates, carbamates, etc.) and with charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), those containing pendant moieties, such as, for example, proteins (e.g., nucleases, toxins, antibodies, signal peptides, poly-L-lysine, etc.), those with intercalators (e.g., acridine, psoralen, etc.), those containing chelators (e.g., metals, radioactive metals, boron, oxidative metals, etc.), those containing alkylators, those with modified linkages (e.g., alpha anomeric nucleic acids, etc.), as well as unmodified forms of the polynucleotide(s). Further, any of the hydroxyl groups ordinarily present in the sugars may be replaced, for example, by phosphonate groups, phosphate groups, protected by standard protecting groups, or activated to prepare additional linkages to additional nucleotides, or may be conjugated to solid supports. The 5′ and 3′ terminal OH can be phosphorylated or substituted with amines or organic capping group moieties of from 1 to 20 carbon atoms. Other hydroxyls may also be derivatized to standard protecting groups. Polynucleotides can also contain analogous forms of ribose or deoxyribose sugars that are generally known in the art, including, for example, 2′-O-methyl-, 2′-O-allyl, 2′-fluoro- or 2′-azido-ribose, carbocyclic sugar analogs, alpha- or beta-anomeric sugars, epimeric sugars such as arabinose, xyloses or lyxoses, pyranose sugars, furanose sugars, sedoheptuloses, acyclic analogs and abasic nucleoside analogs such as methyl riboside. One or more phosphodiester linkages may be replaced by alternative linking groups. These alternative linking groups include, but are not limited to, embodiments wherein phosphate is replaced by P(O)S(“thioate”), P(S)S (“dithioate”), (O)NR 2  (“amidate”), P(O)R, P(O)OR′, CO or CH 2  (“formacetal”), in which each R or R′ is independently H or substituted or unsubstituted alkyl (1-20 C) optionally containing an ether (—O—) linkage, aryl, alkenyl, cycloalkyl, cycloalkenyl or araldyl. Not all linkages in a polynucleotide need be identical. The preceding description applies to all polynucleotides referred to herein, including RNA and DNA. 
     The terms “polypeptide”, “oligopeptide”, “peptide” and “protein” are used interchangeably herein to refer to chains of amino acids of any length. The chain may be linear or branched, it may comprise modified amino acids, and/or may be interrupted by non-amino acids. The terms also encompass an amino acid chain that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art. It is understood that the polypeptides can occur as single chains or associated chains. 
     “Homologous,” in all its grammatical forms and spelling variations, refers to the relationship between two proteins that possess a “common evolutionary origin,” including proteins from superfamilies in the same species of organism, as well as homologous proteins from different species of organism. Such proteins (and their encoding nucleic acids) have sequence homology, as reflected by their sequence similarity, whether in terms of percent identity or by the presence of specific residues or motifs and conserved positions. 
     However, in common usage and in the instant application, the term “homologous,” when modified with an adverb such as “highly,” may refer to sequence similarity and may or may not relate to a common evolutionary origin. 
     The term “sequence similarity,” in all its grammatical forms, refers to the degree of identity or correspondence between nucleic acid or amino acid sequences that may or may not share a common evolutionary origin. 
     “Percent (%) sequence identity” or “percent (%) identical to” with respect to a reference polypeptide (or nucleotide) sequence is defined as the percentage of amino acid residues (or nucleic acids) in a candidate sequence that are identical with the amino acid residues (or nucleic acids) in the reference polypeptide (nucleotide) sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. 
     As used herein, a “host cell” includes an individual cell or cell culture that can be or has been a recipient for vector(s) for incorporation of polynucleotide inserts. The term host cell may refer to the packaging cell line in which the rAAV is produced from the plasmid. In the alternative, the term “host cell” may refer to the target cell in which expression of the transgene is desired. 
     As used herein, a “vector,” refers to a recombinant plasmid or virus that comprises a nucleic acid to be delivered into a host cell, either in vitro or in vivo. A “recombinant viral vector” refers to a recombinant polynucleotide vector comprising one or more heterologous sequences (i.e. a nucleic acid sequence not of viral origin). In the case of recombinant AAV vectors, the recombinant nucleic acid is flanked by at least one inverted terminal repeat sequence (ITR). In some embodiments, the recombinant nucleic acid is flanked by two ITRs. 
     A “recombinant AAV vector (rAAV vector)” refers to a polynucleotide vector based on an adeno-associated virus comprising one or more heterologous sequences (i.e., nucleic acid sequence not of AAV origin) that are flanked by at least one AAV inverted terminal repeat sequence (ITR). Such rAAV vectors can be replicated and packaged into infectious viral particles when present in a host cell that has been infected with a suitable helper virus (or that is expressing suitable helper functions) and that is expressing AAV rep and cap gene products (i.e. AAV Rep and Cap proteins). When a rAAV vector is incorporated into a larger polynucleotide (e.g., in a chromosome or in another vector such as a plasmid used for cloning or transfection), then the rAAV vector may be referred to as a “pro-vector” which can be “rescued” by replication and encapsidation in the presence of AAV packaging functions and suitable helper functions. An rAAV vector can be in any of a number of forms, including, but not limited to, plasmids, linear artificial chromosomes, complexed with lipids, encapsulated within liposomes, and encapsidated in a viral particle, e.g., an AAV particle. An rAAV vector can be packaged into an AAV virus capsid to generate a “recombinant adeno-associated viral particle (rAAV particle)”. 
     An “rAAV virus” or “rAAV viral particle” refers to a viral particle composed of at least one AAV capsid protein and an encapsidated rAAV vector genome. 
     The term “transgene” refers to a polynucleotide that is introduced into a cell and is capable of being transcribed into RNA and optionally, translated and/or expressed under appropriate conditions. In aspects, it confers a desired property to a cell into which it was introduced, or otherwise leads to a desired therapeutic or diagnostic outcome. In another aspect, it may be transcribed into a molecule that mediates RNA interference, such as miRNA, siRNA, or shRNA. 
     The term “vector genome (vg)” as used herein may refer to one or more polynucleotides comprising a set of the polynucleotide sequences of a vector, e.g., a viral vector. A vector genome may be encapsidated in a viral particle. Depending on the particular viral vector, a vector genome may comprise single-stranded DNA, double-stranded DNA, or single-stranded RNA, or double-stranded RNA. A vector genome may include endogenous sequences associated with a particular viral vector and/or any heterologous sequences inserted into a particular viral vector through recombinant techniques. For example, a recombinant AAV vector genome may include at least one ITR sequence flanking a promoter, a stuffer, a sequence of interest (e.g., an RNAi), and a polyadenylation sequence. A complete vector genome may include a complete set of the polynucleotide sequences of a vector. In some embodiments, the nucleic acid titer of a viral vector may be measured in terms of vg/mL. Methods suitable for measuring this titer are known in the art (e.g., quantitative PCR). 
     An “inverted terminal repeat” or “ITR” sequence is a term well understood in the art and refers to relatively short sequences found at the termini of viral genomes which are in opposite orientation. 
     An “AAV inverted terminal repeat (ITR)” sequence, a term well-understood in the art, is an approximately 145-nucleotide sequence that is present at both termini of the native single-stranded AAV genome. The outermost 125 nucleotides of the ITR can be present in either of two alternative orientations, leading to heterogeneity between different AAV genomes and between the two ends of a single AAV genome. The outermost 125 nucleotides also contains several shorter regions of self-complementarity (designated A, A′, B, B′, C, C and D regions), allowing intrastrand base-pairing to occur within this portion of the ITR. 
     A “helper virus” for AAV refers to a virus that allows AAV (which is a defective parvovirus) to be replicated and packaged by a host cell. A number of such helper viruses are known in the art. 
     As used herein, “expression control sequence” means a nucleic acid sequence that directs transcription of a nucleic acid. An expression control sequence can be a promoter, such as a constitutive promoter, or an enhancer. The expression control sequence is operably linked to the nucleic acid sequence to be transcribed. 
     As used herein, “isolated molecule” (where the molecule is, for example, a polypeptide, a polynucleotide, or fragment thereof) is a molecule that by virtue of its origin or source of derivation (1) is not associated with one or more naturally associated components that accompany it in its native state, (2) is substantially free of one or more other molecules from the same species (3) is expressed by a cell from a different species, or (4) does not occur in nature. 
     As used herein, “purify,” and grammatical variations thereof, refers to the removal, whether completely or partially, of at least one impurity from a mixture containing the polypeptide and one or more impurities, which thereby improves the level of purity of the polypeptide in the composition (i.e., by decreasing the amount (ppm) of impurity(ies) in the composition). 
     As used herein, “substantially pure” refers to material which is at least 50% pure (i.e., free from contaminants), more preferably, at least 90% pure, more preferably, at least 95% pure, yet more preferably, at least 98% pure, and most preferably, at least 99% pure. 
     The terms “patient”, “subject”, or “individual” are used interchangeably herein and refer to either a human or a non-human animal. These terms include mammals, such as humans, non-human primates, laboratory animals, livestock animals (including bovines, porcines, camels, etc.), companion animals (e.g., canines, felines, other domesticated animals, etc.) and rodents (e.g., mice and rats). In some embodiments, the subject is a human that is at least 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90 or 95 years of age. 
     In one embodiment, the subject has, or is at risk of developing a disease of the eye. A disease of the eye, includes, without limitation, retinitis pigmentosa, rod-cone dystrophy, Leber&#39;s congenital amaurosis, Usher&#39;s syndrome, Bardet-Biedl Syndrome, Best disease, retinoschisis, Stargardt disease (autosomal dominant or autosomal recessive), untreated retinal detachment, pattern dystrophy, cone-rod dystrophy, achromatopsia, ocular albinism, enhanced S cone syndrome, diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, sickle cell retinopathy, Congenital Stationary Night Blindness, glaucoma, or retinal vein occlusion. In another embodiment, the subject has, or is at risk of developing glaucoma, Leber&#39;s hereditary optic neuropathy, lysosomal storage disorder, or peroxisomal disorder. In another embodiment, the subject is in need of optogenetic therapy. In another embodiment, the subject has shown clinical signs of a disease of the eye. 
     In some embodiments, the subject has, or is at risk of developing a renal disease or complication. In some embodiments, the renal disease or complication is associated with AMD or aHUS. 
     In some embodiments, the subject has, or is at risk of developing AMD or aHUS. 
     Clinical signs of a disease of the eye include, but are not limited to, decreased peripheral vision, decreased central (reading) vision, decreased night vision, loss of color perception, reduction in visual acuity, decreased photoreceptor function, and pigmentary changes. In one embodiment, the subject shows degeneration of the outer nuclear layer (ONL). In another embodiment, the subject has been diagnosed with a disease of the eye. In yet another embodiment, the subject has not yet shown clinical signs of a disease of the eye. 
     As used herein, the terms “prevent”, “preventing” and “prevention” refer to the prevention of the recurrence or onset of, or a reduction in one or more symptoms of a disease or condition (e.g., a disease of the eye) in a subject as result of the administration of a therapy (e.g., a prophylactic or therapeutic agent). For example, in the context of the administration of a therapy to a subject for an infection, “prevent”, “preventing” and “prevention” refer to the inhibition or a reduction in the development or onset of a disease or condition (e.g., a disease of the eye), or the prevention of the recurrence, onset, or development of one or more symptoms of a disease or condition (e.g., a disease of the eye), in a subject resulting from the administration of a therapy (e.g., a prophylactic or therapeutic agent), or the administration of a combination of therapies (e.g., a combination of prophylactic or therapeutic agents). 
     “Treating” a condition or patient refers to taking steps to obtain beneficial or desired results, including clinical results. With respect to a disease or condition (e.g., a disease of the eye), treatment refers to the reduction or amelioration of the progression, severity, and/or duration of an infection (e.g., a disease of the eye or symptoms associated therewith), or the amelioration of one or more symptoms resulting from the administration of one or more therapies (including, but not limited to, the administration of one or more prophylactic or therapeutic agents). 
     “Administering” or “administration of” a substance, a compound or an agent to a subject can be carried out using one of a variety of methods known to those skilled in the art. For example, a compound or an agent can be administered intravitreally or subretinally. In particular embodiments, the compound or agent is administered intravitreally. In some embodiments, administration may be local. In other embodiments, administration may be systemic. Administering can also be performed, for example, once, a plurality of times, and/or over one or more extended periods. In some aspects, the administration includes both direct administration, including self-administration, and indirect administration, including the act of prescribing a drug. For example, as used herein, a physician who instructs a patient to self-administer a drug, or to have the drug administered by another and/or who provides a patient with a prescription for a drug is administering the drug to the patient. 
     As used herein, the term “ocular cells” refers to any cell in, or associated with the function of, the eye. The term may refer to any one or more of photoreceptor cells, including rod, cone and photosensitive ganglion cells, retinal pigment epithelium (RPE) cells, glial cells, Muller cells, bipolar cells, horizontal cells, amacrine cells. In one embodiment, the ocular cells are bipolar cells. In another embodiment, the ocular cells are horizontal cells. In another embodiment, the ocular cells are ganglion cells. In particular embodiments, the cells are RPE cells. 
     Each embodiment described herein may be used individually or in combination with any other embodiment described herein. 
     Construction of rAAV Vectors 
     The disclosure provides recombinant AAV (rAAV) vectors comprising a complement system gene (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5), a splice variant (e.g. FHL1), or a fragment thereof, under the control of a suitable promoter to direct the expression of the complement system gene, splice variant, or fragment thereof in the eye. The disclosure further provides a therapeutic composition comprising an rAAV vector comprising a complement system gene, a splice variant, or a fragment thereof (e.g. CFH, HILL FHR1, FHR2, FHR3, FHR4, or FHR5) under the control of a suitable promoter. A variety of rAAV vectors may be used to deliver the desired complement system gene to the eye and to direct its expression. More than 30 naturally occurring serotypes of AAV from humans and non-human primates are known. Many natural variants of the AAV capsid exist, and an rAAV vector of the disclosure may be designed based on an AAV with properties specifically suited for ocular cells. In certain embodiments, the complement system gene is a splice variant (e.g. FHL1, which is a truncated splice variant of CFH). 
     In general, an rAAV vector is comprised of, in order, a 5′ adeno-associated virus inverted terminal repeat, a transgene or gene of interest encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof operably linked to a sequence which regulates its expression in a target cell, and a 3′ adeno-associated virus inverted terminal repeat. In addition, the rAAV vector may preferably have a polyadenylation sequence. Generally, rAAV vectors should have one copy of the AAV ITR at each end of the transgene or gene of interest, in order to allow replication, packaging, and efficient integration into cell chromosomes. Within preferred embodiments of the disclosure, the transgene sequence encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof will be of about 2 to 5 kb in length (or alternatively, the transgene may additionally contain a “stuffer” or “filler” sequence to bring the total size of the nucleic acid sequence between the two ITRs to between 2 and 5 kb). Alternatively, the transgene encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof may be composed of the same heterologous sequence several times (e.g., two nucleic acid molecules of a complement system gene separated by a ribosomal readthrough stop codon, or alternatively, by an Internal Ribosome Entry Site or “IRES”), or several different heterologous sequences (e.g., different complement system members such as FHL1, separated by a ribosomal readthrough stop codon or an IRES). 
     Recombinant AAV vectors of the present disclosure may be generated from a variety of adeno-associated viruses. For example, ITRs from any AAV serotype are expected to have similar structures and functions with regard to replication, integration, excision and transcriptional mechanisms. Examples of AAV serotypes include AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11 and AAV12. In some embodiments, the rAAV vector is generated from serotype AAV1, AAV2, AAV4, AAV5, or AAV8. These serotypes are known to target photoreceptor cells or the retinal pigment epithelium. In particular embodiments, the rAAV vector is generated from serotype AAV2. In certain embodiments, the AAV serotypes include AAVrh8, AAVrh8R or AAVrh10. It will also be understood that the rAAV vectors may be chimeras of two or more serotypes selected from serotypes AAV1 through AAV12. The tropism of the vector may be altered by packaging the recombinant genome of one serotype into capsids derived from another AAV serotype. In some embodiments, the ITRs of the rAAV virus may be based on the ITRs of any one of AAV1-12 and may be combined with an AAV capsid selected from any one of AAV1-12, AAV-DJ, AAV-DJ8, AAV-DJ9 or other modified serotypes. In certain embodiments, any AAV capsid serotype may be used with the vectors of the disclosure. Examples of AAV serotypes include AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV-DJ, AAV-DJ8, AAV-DJ9, AAVrh8, AAVrh8R or AAVrh10. In certain embodiments, the AAV capsid serotype is AAV2. 
     Desirable AAV fragments for assembly into vectors may include the cap proteins, including the vp1, vp2, vp3 and hypervariable regions, the rep proteins, including rep 78, rep 68, rep 52, and rep 40, and the sequences encoding these proteins. These fragments may be readily utilized in a variety of vector systems and host cells. Such fragments maybe used, alone, in combination with other AAV serotype sequences or fragments, or in combination with elements from other AAV or non-AAV viral sequences. As used herein, artificial AAV serotypes include, without limitation, AAV with a non-naturally occurring capsid protein. 
     Such an artificial capsid may be generated by any suitable technique using a selected AAV sequence (e.g., a fragment of a vp1 capsid protein) in combination with heterologous sequences which may be obtained from a different selected AAV serotype, non-contiguous portions of the same AAV serotype, from a non-AAV viral source, or from a non-viral source. An artificial AAV serotype may be, without limitation, a pseudotyped AAV, a chimeric AAV capsid, a recombinant AAV capsid, or a “humanized” AAV capsid. Pseudotyped vectors, wherein the capsid of one AAV is replaced with a heterologous capsid protein, are useful in the disclosure. In some embodiments, the AAV is AAV2/5. In another embodiment, the AAV is AAV2/8. When pseudotyping an AAV vector, the sequences encoding each of the essential rep proteins may be supplied by different AAV sources (e.g., AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8). For example, the rep78/68 sequences may be from AAV2, whereas the rep52/40 sequences may be from AAV8. 
     In one embodiment, the vectors of the disclosure contain, at a minimum, sequences encoding a selected AAV serotype capsid, e.g., an AAV2 capsid or a fragment thereof. In another embodiment, the vectors of the disclosure contain, at a minimum, sequences encoding a selected AAV serotype rep protein, e.g., AAV2 rep protein, or a fragment thereof. Optionally, such vectors may contain both AAV cap and rep proteins. In vectors in which both AAV rep and cap are provided, the AAV rep and AAV cap sequences can both be of one serotype origin, e.g., all AAV2 origin. In certain embodiments, the vectors may comprise rep sequences from an AAV serotype which differs from that which is providing the cap sequences. In some embodiments, the rep and cap sequences are expressed from separate sources (e.g., separate vectors, or a host cell and a vector). In some embodiments, these rep sequences are fused in frame to cap sequences of a different AAV serotype to form a chimeric AAV vector, such as AAV2/8 described in U.S. Pat. No. 7,282,199, which is incorporated by reference herein. Examples of AAV serotypes include AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV-DJ, AAV-DJ8, AAV-DJ9, AAVrh8, AAVrh8R or AAVrh10. In some embodiments, the cap is derived from AAV2. 
     In some embodiments, any of the vectors disclosed herein includes a spacer, i.e., a DNA sequence interposed between the promoter and the rep gene ATG start site. In some embodiments, the spacer may be a random sequence of nucleotides, or alternatively, it may encode a gene product, such as a marker gene. In some embodiments, the spacer may contain genes which typically incorporate start/stop and polyA sites. In some embodiments, the spacer may be a non-coding DNA sequence from a prokaryote or eukaryote, a repetitive non-coding sequence, a coding sequence without transcriptional controls or a coding sequence with transcriptional controls. In some embodiments, the spacer is a phage ladder sequences or a yeast ladder sequence. In some embodiments, the spacer is of a size sufficient to reduce expression of the rep78 and rep68 gene products, leaving the rep52, rep40 and cap gene products expressed at normal levels. In some embodiments, the length of the spacer may therefore range from about 10 bp to about 10.0 kbp, preferably in the range of about 100 bp to about 8.0 kbp. In some embodiments, the spacer is less than 2 kbp in length. 
     In certain embodiments, the capsid is modified to improve therapy. The capsid may be modified using conventional molecular biology techniques. In certain embodiments, the capsid is modified for minimized immunogenicity, better stability and particle lifetime, efficient degradation, and/or accurate delivery of the transgene encoding the complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or biologically active fragment thereof to the nucleus. In some embodiments, the modification or mutation is an amino acid deletion, insertion, substitution, or any combination thereof in a capsid protein. A modified polypeptide may comprise 1, 2, 3, 4, 5, up to 10, or more amino acid substitutions and/or deletions and/or insertions. A “deletion” may comprise the deletion of individual amino acids, deletion of small groups of amino acids such as 2, 3, 4 or 5 amino acids, or deletion of larger amino acid regions, such as the deletion of specific amino acid domains or other features. An “insertion” may comprise the insertion of individual amino acids, insertion of small groups of amino acids such as 2, 3, 4 or 5 amino acids, or insertion of larger amino acid regions, such as the insertion of specific amino acid domains or other features. A “substitution” comprises replacing a wild type amino acid with another (e.g., a non-wild type amino acid). In some embodiments, the another (e.g., non-wild type) or inserted amino acid is Ala (A), His (H), Lys (K), Phe (F), Met (M), Thr (T), Gln (Q), Asp (D), or Glu (E). In some embodiments, the another (e.g., non-wild type) or inserted amino acid is A. In some embodiments, the another (e.g., non-wild type) amino acid is Arg (R), Asn (N), Cys (C), Gly (G), Ile (I), Leu (L), Pro (P), Ser (S), Trp (W), Tyr (Y), or Val (V). Conventional or naturally occurring amino acids are divided into the following basic groups based on common side-chain properties: (1) non-polar: Norleucine, Met, Ala, Val, Leu, He; (2) polar without charge: Cys, Ser, Thr, Asn, Gin; (3) acidic (negatively charged): Asp, Glu; (4) basic (positively charged): Lys, Arg; and (5) residues that influence chain orientation: Gly, Pro; and (6) aromatic: Trp, Tyr, Phe, His. Conventional amino acids include L or D stereochemistry. In some embodiments, the another (e.g., non-wild type) amino acid is a member of a different group (e.g., an aromatic amino acid is substituted for a non-polar amino acid). Substantial modifications in the biological properties of the polypeptide are accomplished by selecting substitutions that differ significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a β-sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain. Naturally occurring residues are divided into groups based on common side-chain properties: (1) Non-polar: Norleucine, Met, Ala, Val, Leu, Ile; (2) Polar without charge: Cys, Ser, Thr, Asn, Gln; (3) Acidic (negatively charged): Asp, Glu; (4) Basic (positively charged): Lys, Arg; (5) Residues that influence chain orientation: Gly, Pro; and (6) Aromatic: Trp, Tyr, Phe, His. In some embodiments, the another (e.g., non-wild type) amino acid is a member of a different group (e.g., a hydrophobic amino acid for a hydrophilic amino acid, a charged amino acid for a neutral amino acid, an acidic amino acid for a basic amino acid, etc.). In some embodiments, the another (e.g., non-wild type) amino acid is a member of the same group (e.g., another basic amino acid, another acidic amino acid, another neutral amino acid, another charged amino acid, another hydrophilic amino acid, another hydrophobic amino acid, another polar amino acid, another aromatic amino acid or another aliphatic amino acid). In some embodiments, the another (e.g., non-wild type) amino acid is an unconventional amino acid. Unconventional amino acids are non-naturally occurring amino acids. Examples of an unconventional amino acid include, but are not limited to, aminoadipic acid, beta-alanine, beta-aminopropionic acid, aminobutyric acid, piperidinic acid, aminocaprioic acid, aminoheptanoic acid, aminoisobutyric acid, aminopimelic acid, citrulline, diaminobutyric acid, desmosine, diaminopimelic acid, diaminopropionic acid, N-ethylglycine, N-ethylaspargine, hyroxylysine, allo-hydroxylysine, hydroxyproline, isodesmosine, allo-isoleucine, N-methylglycine, sarcosine, N-methylisoleucine, N-methylvaline, norvaline, norleucine, orithine, 4-hydroxyproline, γ-carboxyglutamate, ε-N,N,N-trimethyllysine, ε-N-acetyllysine, O-phosphoserine, N-acetylserine, N-formylmethionine, 3-methylhistidine, 5-hydroxylysine, σ-N-methylarginine, and other similar amino acids and amino acids (e.g., 4-hydroxyproline). In some embodiments, one or more amino acid substitutions are introduced into one or more of VP1, VP2 and VP3. In one aspect, a modified capsid protein comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 conservative or non-conservative substitutions relative to the wild-type polypeptide. In another aspect, the modified capsid polypeptide of the disclosure comprises modified sequences, wherein such modifications can include both conservative and non-conservative substitutions, deletions, and/or additions, and typically include peptides that share at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 87%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the corresponding wild-type capsid protein. 
     In some embodiments, the recombinant AAV vector, rep sequences, cap sequences, and helper functions required for producing the rAAV of the disclosure may be delivered to the packaging host cell using any appropriate genetic element (vector). In some embodiments, a single nucleic acid encoding all three capsid proteins (e.g., VP1, VP2 and VP3) is delivered into the packaging host cell in a single vector. In some embodiments, nucleic acids encoding the capsid proteins are delivered into the packaging host cell by two vectors; a first vector comprising a first nucleic acid encoding two capsid proteins (e.g., VP1 and VP2) and a second vector comprising a second nucleic acid encoding a single capsid protein (e.g., VP3). In some embodiments, three vectors, each comprising a nucleic acid encoding a different capsid protein, are delivered to the packaging host cell. The selected genetic element may be delivered by any suitable method, including those described herein. The methods used to construct any embodiment of this disclosure are known to those with skill in nucleic acid manipulation and include genetic engineering, recombinant engineering, and synthetic techniques. See, e.g., Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, N.Y. Similarly, methods of generating rAAV virions are well known and the selection of a suitable method is not a limitation on the present disclosure. See, e.g., K. Fisher et al, J. Virol., 70:520-532 (1993) and U.S. Pat. No. 5,478,745. 
     In some embodiments, recombinant AAVs may be produced using the triple transfection method (described in detail in U.S. Pat. No. 6,001,650). Typically, the recombinant AAVs are produced by transfecting a host cell with an recombinant AAV vector (comprising a transgene) to be packaged into AAV particles, an AAV helper function vector, and an accessory function vector. An AAV helper function vector encodes the “AAV helper function” sequences (e.g., rep and cap), which function in trans for productive AAV replication and encapsidation. Preferably, the AAV helper function vector supports efficient AAV vector production without generating any detectable wild-type AAV virions (e.g., AAV virions containing functional rep and cap genes). In some embodiments, vectors suitable for use with the present disclosure may be pHLP19, described in U.S. Pat. No. 6,001,650 and pRep6cap6 vector, described in U.S. Pat. No. 6,156,303, the entirety of both incorporated by reference herein. The accessory function vector encodes nucleotide sequences for non-AAV derived viral and/or cellular functions upon which AAV is dependent for replication (e.g., “accessory functions”). The accessory functions include those functions required for AAV replication, including, without limitation, those moieties involved in activation of AAV gene transcription, stage specific AAV mRNA splicing, AAV DNA replication, synthesis of cap expression products, and AAV capsid assembly. Viral-based accessory functions can be derived from any of the known helper viruses such as adenovirus, herpesvirus (other than herpes simplex virus type-1), and vaccinia virus. 
     Cells may also be transfected with a vector (e.g., helper vector) which provides helper functions to the AAV. The vector providing helper functions may provide adenovirus functions, including, e.g., E1a, E1b, E2a, E4ORF6. The sequences of adenovirus gene providing these functions may be obtained from any known adenovirus serotype, such as serotypes 2, 3, 4, 7, 12 and 40, and further including any of the presently identified human types known in the art. Thus, in some embodiments, the methods involve transfecting the cell with a vector expressing one or more genes necessary for AAV replication, AAV gene transcription, and/or AAV packaging. 
     An rAAV vector of the disclosure is generated by introducing a nucleic acid sequence encoding an AAV capsid protein, or fragment thereof, a functional rep gene or a fragment thereof; a minigene composed of, at a minimum, AAV inverted terminal repeats (ITRs) and a transgene encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof; and sufficient helper functions to permit packaging of the minigene into the AAV capsid, into a host cell. The components required for packaging an AAV minigene into an AAV capsid may be provided to the host cell in trans. Alternatively, any one or more of the required components (e.g., minigene, rep sequences, cap sequences, and/or helper functions) may be provided by a stable host cell which has been engineered to contain one or more of the required components using methods known to those of skill in the art. 
     In some embodiments, such a stable host cell will contain the required component(s) under the control of an inducible promoter. Alternatively, the required component(s) may be under the control of a constitutive promoter. Examples of suitable inducible and constitutive promoters are provided herein, in the discussion below of regulator elements suitable for use with the transgene, i.e., a nucleic acid encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or biologically active fragment thereof. In still another alternative, a selected stable host cell may contain selected components under the control of a constitutive promoter and other selected components under the control of one or more inducible promoters. For example, a stable host cell may be generated which is derived from 293 cells (which contain E1 helper functions under the control of a constitutive promoter), but which contains the rep and/or cap proteins under the control of inducible promoters. Still other stable host cells may be generated by one of skill in the art. 
     The minigene, rep sequences, cap sequences, and helper functions required for producing the rAAV of the disclosure may be delivered to the packaging host cell in the form of any genetic element which transfers the sequences. The selected genetic element may be delivered by any suitable method known in the art. See, e.g., Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, N.Y. Similarly, methods of generating rAAV virions are well known and the selection of a suitable method is not a limitation on the present disclosure. See, e.g., K. Fisher et al, 1993 J. Virol, 70:520-532 and U.S. Pat. No. 5,478,745, among others. These publications are incorporated by reference herein. 
     Unless otherwise specified, the AAV ITRs, and other selected AAV components described herein, may be readily selected from among any AAV serotype, including, without limitation, AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV10, AAV11, AAV12, AAV-DJ, AAV-DJ8, AAV-DJ9, AAVrh8, AAVrh8R or AAVrh10 or other known and unknown AAV serotypes. These ITRs or other AAV components may be readily isolated using techniques available to those of skill in the art from an AAV serotype. Such AAV may be isolated or obtained from academic, commercial, or public sources (e.g., the American Type Culture Collection, Manassas, Va.). Alternatively, the AAV sequences may be obtained through synthetic or other suitable means by reference to published sequences such as are available in the literature or in databases such as, e.g., GenBank, PubMed, or the like. 
     The minigene is composed of, at a minimum, a transgene encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof, as described above, and its regulatory sequences, and 5′ and 3′ AAV inverted terminal repeats (ITRs). In one desirable embodiment, the ITRs of AAV serotype 2 are used. However, ITRs from other suitable serotypes may be selected. The minigene is packaged into a capsid protein and delivered to a selected host cell. 
     In some embodiments, regulatory sequences are operably linked to the transgene encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof. The regulatory sequences may include conventional control elements which are operably linked to the complement system gene, splice variant, or a fragment thereof in a manner which permits its transcription, translation and/or expression in a cell transfected with the vector or infected with the virus produced by the disclosure. As used herein, “operably linked” sequences include both expression control sequences that are contiguous with the gene of interest and expression control sequences that act in trans or at a distance to control the gene of interest. Expression control sequences include appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation (polyA) signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (i.e., Kozak consensus sequence); sequences that enhance protein stability; and when desired, sequences that enhance secretion of the encoded product. Numerous expression control sequences, including promoters, are known in the art and may be utilized. 
     The regulatory sequences useful in the constructs of the present disclosure may also contain an intron, desirably located between the promoter/enhancer sequence and the gene. In some embodiments, the intron sequence is derived from SV-40, and is a 100 bp mini-intron splice donor/splice acceptor referred to as SD-SA. Another suitable sequence includes the woodchuck hepatitis virus post-transcriptional element. (See, e.g., L. Wang and I. Verma, 1999 Proc. Natl. Acad. Sci., USA, 96:3906-3910). PolyA signals may be derived from many suitable species, including, without limitation SV-40, human and bovine. 
     Another regulatory component of the rAAV useful in the method of the disclosure is an internal ribosome entry site (IRES). An IRES sequence, or other suitable systems, may be used to produce more than one polypeptide from a single gene transcript (for example, to produce more than one complement system polypeptides). An IRES (or other suitable sequence) is used to produce a protein that contains more than one polypeptide chain or to express two different proteins from or within the same cell. An exemplary IRES is the poliovirus internal ribosome entry sequence, which supports transgene expression in photoreceptors, RPE and ganglion cells. Preferably, the IRES is located 3′ to the transgene in the rAAV vector. 
     In some embodiments, expression of the transgene encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof is driven by a separate promoter (e.g., a viral promoter). In certain embodiments, any promoters suitable for use in AAV vectors may be used with the vectors of the disclosure. The selection of the transgene promoter to be employed in the rAAV may be made from among a wide number of constitutive or inducible promoters that can express the selected transgene in the desired ocular cell. Examples of suitable promoters are described below. 
     Other regulatory sequences useful in the disclosure include enhancer sequences Enhancer sequences useful in the disclosure include the 1RBP enhancer (Nicoud 2007, cited above), immediate early cytomegalovirus enhancer, one derived from an immunoglobulin gene or SV40 enhancer, the cis-acting element identified in the mouse proximal promoter, etc. 
     Selection of these and other common vector and regulatory elements are well-known and many such sequences are available. See, e.g., Sambrook et al, and references cited therein at, for example, pages 3.18-3.26 and 16, 17-16.27 and Ausubel et al., Current Protocols in Molecular Biology, John Wiley &amp; Sons, New York, 1989). 
     The rAAV vector may also contain additional sequences, for example from an adenovirus, which assist in effecting a desired function for the vector. Such sequences include, for example, those which assist in packaging the rAAV vector in adenovirus-associated virus particles. 
     The rAAV vector may also contain a reporter sequence for co-expression, such as but not limited to lacZ, GFP, CFP, YFP, RFP, mCherry, tdTomato, etc. In some embodiments, the rAAV vector may comprise a selectable marker. In some embodiments, the selectable marker is an antibiotic-resistance gene. In some embodiments, the antibiotic-resistance gene is an ampicillin-resistance gene. In some embodiments, the ampicillin-resistance gene is beta-lactamase. 
     In some embodiments, the rAAV particle is an ssAAV. In some embodiments, the rAAV particle is a self-complementary AAV (sc-AAV) (See, US 2012/0141422 which is incorporated herein by reference). Self-complementary vectors package an inverted repeat genome that can fold into dsDNA without the requirement for DNA synthesis or base-pairing between multiple vector genomes. Because scAAV have no need to convert the single-stranded DNA (ssDNA) genome into double-stranded DNA (dsDNA) prior to expression, they are more efficient vectors. However, the trade-off for this efficiency is the loss of half the coding capacity of the vector, ScAAV are useful for small protein-coding genes (up to −55 kd) and any currently available RNA-based therapy. 
     The single-stranded nature of the AAV genome may impact the expression of rAAV vectors more than any other biological feature. Rather than rely on potentially variable cellular mechanisms to provide a complementary-strand for rAAV vectors, it has now been found that this problem may be circumvented by packaging both strands as a single DNA molecule. In the studies described herein, an increased efficiency of transduction from duplexed vectors over conventional rAAV was observed in HeLa cells (5-140 fold). More importantly, unlike conventional single-stranded AAV vectors, inhibitors of DNA replication did not affect transduction from the duplexed vectors of the invention. In addition, the inventive duplexed parvovirus vectors displayed a more rapid onset and a higher level of transgene expression than did rAAV vectors in mouse hepatocytes in vivo. All of these biological attributes support the generation and characterization of a new class of parvovirus vectors (delivering duplex DNA) that significantly contribute to the ongoing development of parvovirus-based gene delivery systems. 
     Overall, a novel type of parvovirus vector that carries a duplexed genome, which results in co-packaging strands of plus and minus polarity tethered together in a single molecule, has been constructed and characterized by the investigations described herein. Accordingly, the present invention provides a parvovirus particle comprising a parvovirus capsid (e.g., an AAV capsid) and a vector genome encoding a heterologous nucleotide sequence, where the vector genome is self-complementary, i.e., the vector genome is a dimeric inverted repeat. The vector genome is preferably approximately the size of the wild-type parvovirus genome (e.g., the AAV genome) corresponding to the parvovirus capsid into which it will be packaged and comprises an appropriate packaging signal. The present invention further provides the vector genome described above and templates that encode the same. 
     rAAV vectors useful in the methods of the disclosure are further described in PCT publication No. WO2015168666 and PCT publication no. WO2014011210, the contents of which are incorporated by reference herein. 
     In some embodiments, any of the vectors disclosed herein is capable of inducing at least 20%, 50%, 100%, 150%, 200%, 250%, 300%, 400%, 500%, 700%, 900%, 1000%, 1100%, 1500%, or 2000% higher expression of CFH or FHL in a target cell (e.g., an RPE or liver cell) as compared to the endogenous expression of CFH or FHL in the target cell. In some embodiments, expression of any of the vectors disclosed herein in a target cell (e.g., an RPE or liver cell) results in at least 20%, 50%, 100%, 150%, 200%, 250%, 300%, 400%, 500%, 700%, 900%, 1000%, 1100%, 1500%, or 2000% higher levels of CFH or FHL activity in the target cell as compared to endogenous levels of CFH or FHL activity in the target cell. 
     Complement System Genes 
     In the search for causative factors associated with age related macular degeneration, epidemiological and genetic studies have identified numerous common and rare alleles for AMD at or near several complement genes (CFH, C2/CFB, C3, CFI, and C9). Genome-wide association studies (GWAS) identified that a single nucleotide polymorphism (SNP), Y402H, on a gene encoding CFH. The Y402H SNP confers a two to sevenfold increased risk for AMD development (Klein R J et al. Science. 2005; 308:385-9; Edwards A O et al. Science. 2005; 308:421-4; Hageman G S et al. PNAS. 2005; 102:7227-32; Haines J L et al. Science. 2005; 308:419-21). Additional GWAS led to the identification of other variants on the CFH locus which are associated with advanced AMD (Raychaudhuri S et al. Nat Genet. 2011; 43: 1232-6). Overall, these studies have identified that variants near six complement genes (CFH, C2/CFB, C3, CFI, and C9) together accounts for nearly 60% of the AMD genetic risk (Fritsche L G et al. Annu Rev Genomics Hum Genet. 2014; 15:151-71). 
     Complement system genes (e.g. CFH, FHL-1, FHR1, FHR2, FHR3, FHR4, or FHR5), splice variants (e.g. FHL1), or fragments thereof are provided as transgenes in the recombinant AAV (rAAV) vectors of the disclosure. The transgene is a nucleic acid sequence, heterologous to the vector sequences flanking the transgene, which encodes a polypeptide, protein, or other product, of interest. The nucleic acid coding sequence is operatively linked to regulatory components in a manner which permits transgene transcription, translation, and/or expression in a target cell (e.g. an ocular cell). The heterologous nucleic acid sequence (transgene) can be derived from any organism. In certain embodiments, the transgene is derived from a human. In certain embodiments, the transgene encodes a mature form of a complement protein. In some embodiments, the transgene encodes a polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 92%, 95%, or 97% identical to the amino acid sequence of SEQ ID NO: 33, or a biologically active fragment thereof. In some embodiments, the transgene encodes a polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 92%, 95%, or 97% identical to the amino acid sequence of SEQ ID NO: 34, or a biologically active fragment thereof. In certain embodiments, the rAAV vector may comprise one or more transgenes. 
     In some embodiments, the transgene comprises more than one complement system gene, splice variant, or fragments derived from more than one complement system gene. This may be accomplished using a single vector carrying two or more heterologous sequences, or using two or more rAAV vectors each carrying one or more heterologous sequences. In some embodiments, in addition to a complement system gene, splice variant, or fragment thereof, the rAAV vector may also encode additional proteins, peptides, RNA, enzymes, or catalytic RNAs. Desirable RNA molecules include shRNA, tRNA, dsRNA, ribosomal RNA, catalytic RNAs, and antisense RNAs. One example of a useful RNA sequence is a sequence which extinguishes expression of a targeted nucleic acid sequence in the treated subject. The additional proteins, peptides, RNA, enzymes, or catalytic RNAs and the complement factor may be encoded by a single vector carrying two or more heterologous sequences, or using two or more rAAV vectors each carrying one or more heterologous sequences. 
     In certain aspects, the disclosure provides a recombinant adeno-associated viral (rAAV) vector encoding a human Complement Factor H or Factor H Like 1 (FHL1) protein or biologically active fragment thereof. In certain embodiments, the vector comprises a nucleotide sequence that is at least 80%, 85%, 90%, 92%, 94%, 95%, 97%, 99% or 100% identical to any of the sequences disclosed herein encoding a CFH or CFHL protein, or biologically active fragments thereof. In certain embodiments, the vector comprises a nucleotide sequence that is at least 80%, 85%, 90%, 92%, 94%, 95%, 97%, 99% or 100% identical to any of SEQ ID Nos: 1-3 or 5, or biologically active fragments thereof. In some embodiments, the vector comprises a nucleotide sequence that is at least 70%, 75%, 80%, 85%, 90%, 92%, 94%, 95%, 97%, 99% or 100% identical to SEQ ID NO: 1, or biologically active fragments thereof. In some embodiments, the vector comprises a nucleotide sequence that is at least 70%, 75%, 80%, 85%, 90%, 92%, 94%, 95%, 97%, 99% or 100% identical to SEQ ID NO: 2, or biologically active fragments thereof. In some embodiments, the vector comprises a nucleotide sequence that is at least 70%, 75%, 80%, 85%, 90%, 92%, 94%, 95%, 97%, 99% or 100% identical to SEQ ID NO: 3, or biologically active fragments thereof. In some embodiments, the vector comprises a nucleotide sequence that is at least 70%, 75%, 80%, 85%, 90%, 92%, 94%, 95%, 97%, 99% or 100% identical to SEQ ID NO: 5, or biologically active fragments thereof. In certain embodiments the vector comprises a nucleotide sequence that is at least 80% identical to the nucleotide sequence of SEQ ID NO: 1-3 or 5, or a fragment thereof. In certain embodiments, the nucleotide sequence is at least 90% identical to the nucleotide sequence of SEQ ID NO: 1-3 or 5, or a fragment thereof. In certain embodiments, the nucleotide sequence is at least 95% identical to the nucleotide sequence of SEQ ID NO: 1-3 or 5, or a fragment thereof. In certain embodiments, the nucleotide sequence is the sequence of SEQ ID NO: 1-3 or 5, or a fragment thereof. In certain embodiments, the vector encodes a CFH or an FHL1 protein or biologically active fragment thereof comprising at least four CCP domains. In certain embodiments, the vector encodes CFH or an FHL1 protein or biologically active fragment thereof comprising at least five CCP domains. In certain embodiments, the vector encodes a CFH or an FHL1 protein or biologically active fragment thereof comprising at least six CCP domains. In certain embodiments, the vector encodes a CFH or an FHL1 protein or biologically active fragment thereof comprising at least seven CCP domains. In certain embodiments, the vector encodes an FHL1 protein or biologically active fragment thereof comprising at least three CCP domains. In certain embodiments, the vector encodes a CFH or FHL1 protein or biologically active fragment thereof that comprises at least CCPs 1-2 of CFH. In certain embodiments, the vector encodes a biologically active fragment of CFH that comprises at least CCPs 1-4 of CFH. In certain embodiments, the vector encodes a CFH or FHL1 protein or biologically active fragment thereof that comprises at least CCPs 19-20 of CFH. Schmidt C O, Herbert A P, Kavanagh D, Gandy C, Fenton C J, Blaum B S, Lyon M, Uhrin D, Barlow P N. J Immunol, 2008, 181:2610-9. In certain embodiments, the vector encodes a CFH or an FHL1 protein or biologically active fragment thereof comprising the H402 polymorphism. In certain embodiments, the vector encodes a CFH or an FHL1 protein or biologically active fragment thereof comprising the V62 polymorphism. In certain embodiments, the CFH or FHL1 protein or biologically active fragment thereof comprises the amino acid sequence of SEQ ID NO: 4. In certain embodiments, the amino acid sequence of SEQ ID NO: 4 is the C-terminal sequence of the CFH or FHL1 protein. In certain embodiments, the CFH or FHL1 protein or biologically active fragment thereof is capable of diffusing across the Bruch&#39;s membrane. In certain embodiments, the CFH or FHL1 protein or biologically active fragment thereof is capable of binding C3b. In certain embodiments, the CFH or FHL1 protein or biologically active fragment thereof is capable of facilitating the breakdown of C3b. 
     In certain embodiments, the vector comprises a nucleotide sequence that is at least 80%, 85%, 90%, 92%, 94%, 95%, 97%, 99% or 100% identical to any of SEQ ID Nos: 7, 9, 11, 13, 15, 17, 19, or 21-30, or biologically active fragments thereof. 
     Exemplary sequences of transgenes are set forth in SEQ ID NOs: 1-3 or 5. In some embodiments, a transgene of the disclosure comprises the nucleic acid sequence set forth in SEQ ID NO: 1. In some embodiments, a transgene of the disclosure comprises the nucleic acid sequence set forth in SEQ ID NO: 2. In some embodiments, a transgene of the disclosure comprises the nucleic acid sequence set forth in SEQ ID NO: 3. In some embodiments, a transgene of the disclosure comprises the nucleic acid sequence set forth in SEQ ID NO: 5. In some embodiments, a transgene of the disclosure comprises a variant of these sequences, wherein such variants can include can include missense mutations, nonsense mutations, duplications, deletions, and/or additions, and typically include polynucleotides that share at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 87%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the specific nucleic acid sequences set forth in SEQ ID NOs: 1-3 or 5. One of ordinary skill in the art will appreciate that nucleic acid sequences complementary to the nucleic acids, and variants of the nucleic acids are also within the scope of this disclosure. In further embodiments, the nucleic acid sequences of the disclosure can be isolated, recombinant, and/or fused with a heterologous nucleotide sequence. In some embodiments, any of the nucleotides disclosed herein (e.g., SEQ ID Nos: 1-3 or 5) is codon-optimized (e.g., codon-optimized for human expression) 
     In one aspect, a transgene encodes a complement system polypeptide with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid substitutions, deletions, and/or additions relative to the wild-type polypeptide. In some embodiments, a transgene encodes a complement system polypeptide with 1, 2, 3, 4, or 5 amino acid deletions relative to the wild-type polypeptide. In some embodiments, a transgene encodes a polypeptide with 1, 2, 3, 4, or 5 amino acid substitutions relative to the wild-type polypeptide. In some embodiments, a transgene encodes a polypeptide with 1, 2, 3, 4, or 5 amino acid insertions relative to the wild-type polypeptide. Polynucleotides complementary to any of the polynucleotide sequences disclosed herein are also encompassed by the present disclosure. Polynucleotides may be single-stranded (coding or antisense) or double-stranded, and may be DNA (genomic or synthetic), cDNA, or RNA molecules. RNA molecules include mRNA molecules. Additional coding or non-coding sequences may, but need not, be present within a polynucleotide of the present disclosure, and a polynucleotide may, but need not, be linked to other molecules and/or support materials. 
     Two polynucleotide or polypeptide sequences are said to be “identical” if the sequence of nucleotides or amino acids in the two sequences is the same when aligned for maximum correspondence as described below. Comparisons between two sequences are typically performed by comparing the sequences over a comparison window to identify and compare local regions of sequence similarity. A “comparison window” as used herein, refers to a segment of at least about 20 contiguous positions, usually 30 to about 75, or 40 to about 50, in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. 
     Optimal alignment of sequences for comparison may be conducted using the MegAlign® program in the Lasergene® suite of bioinformatics software (DNASTAR®, Inc., Madison, Wis.), using default parameters. This program embodies several alignment schemes described in the following references: Dayhoff, M. O., 1978, A model of evolutionary change in proteins—Matrices for detecting distant relationships. In Dayhoff, M. O. (ed.) Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, Washington D.C. Vol. 5, Suppl. 3, pp. 345-358; Hein J., 1990, Unified Approach to Alignment and Phylogenes pp. 626-645 Methods in Enzymology vol. 183, Academic Press, Inc., San Diego, Calif.; Higgins, D. G. and Sharp, P. M., 1989, CABIOS 5:151-153; Myers, E. W. and Muller W., 1988, CABIOS 4:11-17; Robinson, E. D., 1971, Comb. Theor. 11:105; Santou, N., Nes, M., 1987, Mol. Biol. Evol. 4:406-425; Sneath, P. H. A. and Sokal, R. R., 1973, Numerical Taxonomy the Principles and Practice of Numerical Taxonomy, Freeman Press, San Francisco, Calif.; Wilbur, W. J. and Lipman, D. J., 1983, Proc. Natl. Acad. Sci. USA 80:726-730. 
     Preferably, the “percentage of sequence identity” is determined by comparing two optimally aligned sequences over a window of comparison of at least 20 positions, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (i.e., gaps) of 20 percent or less, usually 5 to 15 percent, or 10 to 12 percent, as compared to the reference sequences (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid bases or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the reference sequence (i.e., the window size) and multiplying the results by 100 to yield the percentage of sequence identity. The transgenes or variants may also, or alternatively, be substantially homologous to a native gene, or a portion or complement thereof. Such polynucleotide variants are capable of hybridizing under moderately stringent conditions to a naturally occurring DNA sequence encoding a complement factor (or a complementary sequence). Suitable “moderately stringent conditions” include prewashing in a solution of 5×SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50° C.-65° C., 5×SSC, overnight; followed by washing twice at 65° C. for 20 minutes with each of 2×, 0.5× and 0.2×SSC containing 0.1% SDS. As used herein, “highly stringent conditions” or “high stringency conditions” are those that: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium dodecyl sulfate at 50° C.; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1% Ficoll/0.1% polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42° C.; or (3) employ 50% formamide, 5×SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5×Denhardt&#39;s solution, sonicated salmon sperm DNA (50 μg/ml), 0.1% SDS, and 10% dextran sulfate at 42° C., with washes at 42° C. in 0.2×SSC (sodium chloride/sodium citrate) and 50% formamide at 55° C., followed by a high-stringency wash consisting of 0.1×SSC containing EDTA at 55° C. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like. 
     It will be appreciated by those of ordinary skill in the art that, as a result of the degeneracy of the genetic code, there are many nucleotide sequences that encode a polypeptide as described herein. Some of these polynucleotides bear minimal homology to the nucleotide sequence of any native gene. Nonetheless, polynucleotides that vary due to differences in codon usage are specifically contemplated by the present disclosure. Further, alleles of the genes comprising the polynucleotide sequences provided herein are within the scope of the present disclosure. Alleles are endogenous genes that are altered as a result of one or more mutations, such as deletions, additions and/or substitutions of nucleotides. The resulting mRNA and protein may, but need not, have an altered structure or function. Alleles may be identified using standard techniques (such as hybridization, amplification and/or database sequence comparison). 
     The nucleic acids/polynucleotides of this disclosure can be obtained using chemical synthesis, recombinant methods, or PCR. Methods of chemical polynucleotide synthesis are well known in the art and need not be described in detail herein. One of skill in the art can use the sequences provided herein and a commercial DNA synthesizer to produce a desired DNA sequence. In other embodiments, nucleic acids of the disclosure also include nucleotide sequences that hybridize under highly stringent conditions to the nucleotide sequences set forth in SEQ ID NOs: 1, 2, 3 and 5, or sequences complementary thereto. One of ordinary skill in the art will readily understand that appropriate stringency conditions which promote DNA hybridization can be varied. For example, one could perform the hybridization at 6.0×sodium chloride/sodium citrate (SSC) at about 45° C., followed by a wash of 2.0×SSC at 50° C. For example, the salt concentration in the wash step can be selected from a low stringency of about 2.0×SSC at 50° C. to a high stringency of about 0.2×SSC at 50° C. In addition, the temperature in the wash step can be increased from low stringency conditions at room temperature, about 22° C., to high stringency conditions at about 65° C. Both temperature and salt may be varied, or temperature or salt concentration may be held constant while the other variable is changed. In one embodiment, the disclosure provides nucleic acids which hybridize under low stringency conditions of 6×SSC at room temperature followed by a wash at 2×SSC at room temperature. 
     Isolated nucleic acids which differ due to degeneracy in the genetic code are also within the scope of the disclosure. For example, a number of amino acids are designated by more than one triplet. Codons that specify the same amino acid, or synonyms (for example, CAU and CAC are synonyms for histidine) may result in “silent” mutations which do not affect the amino acid sequence of the protein. One skilled in the art will appreciate that these variations in one or more nucleotides (up to about 3-5% of the nucleotides) of the nucleic acids encoding a particular protein may exist among members of a given species due to natural allelic variation. Any and all such nucleotide variations and resulting amino acid polymorphisms are within the scope of this disclosure. 
     The present disclosure further provides oligonucleotides that hybridize to a polynucleotide having the nucleotide sequence set forth in SEQ ID NOs: 1, 2, 3 and 5, or to a polynucleotide molecule having a nucleotide sequence which is the complement of a sequence listed above. Such oligonucleotides are at least about 10 nucleotides in length, and preferably from about 15 to about 30 nucleotides in length, and hybridize to one of the aforementioned polynucleotide molecules under highly stringent conditions, i.e., washing in 6×SSC/0.5% sodium pyrophosphate at about 37° C. for about 14-base oligos, at about 48° C. for about 17-base oligos, at about 55° C. for about 20-base oligos, and at about 60° C. for about 23-base oligos. In a preferred embodiment, the oligonucleotides are complementary to a portion of one of the aforementioned polynucleotide molecules. These oligonucleotides are useful for a variety of purposes including encoding or acting as antisense molecules useful in gene regulation, or as primers in amplification of complement system-encoding polynucleotide molecules. 
     In another embodiment, the transgenes useful herein include reporter sequences, which upon expression produce a detectable signal. Such reporter sequences include, without limitation, DNA sequences encoding β-lactamase, β-galactosidase (LacZ), alkaline phosphatase, thymidine kinase, green fluorescent protein (GFP), red fluorescent protein (RFP), chloramphenicol acetyltransferase (CAT), luciferase, membrane bound proteins including, for example, CD2, CD4, CD8, the influenza hemagglutinin protein, and others well known in the art, to which high affinity antibodies directed thereto exist or can be produced by conventional means, and fusion proteins comprising a membrane bound protein appropriately fused to an antigen tag domain from, among others, hemagglutinin or Myc. These coding sequences, when associated with regulatory elements which drive their expression, provide signals detectable by conventional means, including enzymatic, radiographic, colorimetric, fluorescence or other spectrographic assays, fluorescent activating cell sorting assays and immunological assays, including enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA) and immunohistochemistry. For example, where the marker sequence is the LacZ gene, the presence of the vector carrying the signal is detected by assays for beta-galactosidase activity. Where the transgene is green fluorescent protein or luciferase, the vector carrying the signal may be measured visually by color or light production in a luminometer. 
     The complement system gene or fragment thereof (e.g. a gene encoding CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) may be used to correct or ameliorate gene deficiencies, which may include deficiencies in which normal complement system genes are expressed at less than normal levels or deficiencies in which the functional complement system gene product is not expressed. In some embodiments, the transgene sequence encodes a single complement system protein or biologically active fragment thereof. The disclosure further includes using multiple transgenes, e.g., transgenes encoding two or more complement system polypeptides or biologically active fragments thereof. In certain situations, a different transgene may be used to encode different complement proteins or biologically active fragments thereof (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5). Alternatively, different complement proteins (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or biologically active fragments thereof may be encoded by the same transgene. In this case, a single transgene includes the DNA encoding each of the complement proteins (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or biologically active fragments thereof, with the DNA for each protein or functional fragment thereof separated by an internal ribozyme entry site (IRES). This is desirable when the size of the DNA encoding each of the subunits is small, e.g., the total size of the DNA encoding the subunits and the IRES is less than five kilobases. As an alternative to an IRES, the DNA may be separated by sequences encoding a 2A peptide, which self-cleaves in a post-translational event. See, e.g., MX. Donnelly, et al, J. Gen. Virol, 78(Pt 1): 13-21 (January 1997); Furler, S., et al, Gene Ther., 8(11):864-873 (June 2001); Klump H., et al, Gene Ther., 8(10):811-817 (May 2001). This 2A peptide is significantly smaller than an IRES, making it well suited for use when space is a limiting factor. 
     The regulatory sequences include conventional control elements which are operably linked to the transgene encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or biologically active fragment thereof in a manner which permits its transcription, translation and/or expression in a cell transfected with the vector or infected with the virus produced as described herein. As used herein, “operably linked” sequences include both expression control sequences that are contiguous with the gene of interest and expression control sequences that act in trans or at a distance to control the gene of interest. 
     Expression control sequences include appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation (polyA) signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (i.e., Kozak consensus sequence); sequences that enhance protein stability; and when desired, sequences that enhance secretion of the encoded product. A great number of expression control sequences, including promoters, are known in the art and may be utilized. 
     The regulatory sequences useful in the constructs provided herein may also contain an intron, desirably located between the promoter/enhancer sequence and the gene. One desirable intron sequence is derived from SV-40, and is a 100 bp mini-intron splice donor/splice acceptor referred to as SD-SA. In some embodiments, the intron comprises the nucleotide sequence of SEQ ID NO: 10, or a codon-optimized or fragment thereof. Another suitable sequence includes the woodchuck hepatitis virus post-transcriptional element. (See, e.g., L. Wang and I. Verma, 1999 Proc. Natl. Acad. Sci., USA, 96:3906-3910). PolyA signals may be derived from many suitable species, including, without limitation SV-40, human and bovine. 
     Another regulatory component of the rAAV useful in the methods described herein is an internal ribosome entry site (IRES). An IRES sequence, or other suitable systems, may be used to produce more than one polypeptide from a single gene transcript. An IRES (or other suitable sequence) is used to produce a protein that contains more than one polypeptide chain or to express two different proteins from or within the same cell. An exemplary IRES is the poliovirus internal ribosome entry sequence, which supports transgene expression in photoreceptors, RPE and ganglion cells. Preferably, the IRES is located 3′ to the transgene in the rAAV vector. 
     In one embodiment, the AAV comprises a promoter (or a functional fragment of a promoter). The selection of the promoter to be employed in the rAAV may be made from among a wide number of promoters that can express the selected transgene in the desired target cell. In one embodiment, the target cell is an ocular cell. In some embodiments, the target cell is a neuronal cell (i.e., the vector targets neuronal cells). However, in particular embodiments, the target cell is a non-neuronal cell (i.e., the vector does not target neuronal cells). In some embodiments, the target cell is a glial cell, Muller cell, and/or retinal pigment epithelial (RPE) cell. The promoter may be derived from any species, including human. In one embodiment, the promoter is “cell specific”. The term “cell-specific” means that the particular promoter selected for the recombinant vector can direct expression of the selected transgene in a particular cell or ocular cell type. In one embodiment, the promoter is specific for expression of the transgene in photoreceptor cells. In another embodiment, the promoter is specific for expression in the rods and/or cones. In another embodiment, the promoter is specific for expression of the transgene in RPE cells. In another embodiment, the promoter is specific for expression of the transgene in ganglion cells. In another embodiment, the promoter is specific for expression of the transgene in Muller cells. In another embodiment, the promoter is specific for expression of the transgene in bipolar cells. In another embodiment, the promoter is specific for expression of the transgene in ON-bipolar cells. In one embodiment, the promoter is metabotropic glutamate receptor 6 (mGluR6) promoter (see, Vardi et al, mGluR6 Transcripts in Non-neuronal Tissues, J Histochem Cytochem. 2011 December; 59(12): 1076-1086, which is incorporated herein by reference). In another embodiment, the promoter is an enhancer-linked mGluR6 promoter. In another embodiment, the promoter is specific for expression of the transgene in OFF-bipolar cells. In another embodiment, the promoter is specific for expression of the transgene in horizontal cells. In another embodiment, the promoter is specific for expression of the transgene in amacrine cells. In another embodiment, the transgene is expressed in any of the above noted ocular cells. In another embodiment, the promoter is the human G-protein-coupled receptor protein kinase 1 (GRK1) promoter (Genbank Accession number AY327580), In another embodiment, the promoter is the human interphotoreceptor retinoid-binding protein proximal (IRBP) promoter. 
     In some embodiments, the promoter is of a small size, e.g., under 1000 bp, due to the size limitations of the AAV vector. In some embodiments, the promoter is less than 1000, 900, 800, 700, 600, 500, 400 or 300 bp in size. In particular embodiments, the promoter is under 400 bp. In some embodiments, the promoter is a promoter selected from the CRALBP (RLBP), EF1a, HSP70, AAT1, ALB, PCK1, CAG, RPE65, MECP, or sCBA promoter. In some embodiments, the promoter comprises a nucleotide sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity of any one of SEQ ID NOs: 6, 8, 12, 14, 16, 18, 20, 31, 32, or 36 or codon-optimized and/or fragment thereof. In some embodiments, the promoter comprises the nucleotide sequence of any one of SEQ ID NOs: 6, 8, 12, 14, 16, 18, 20, 31, 32, or 36 or codon-optimized and/or fragment thereof. In some embodiments, the promoter is associated with strong expression in the eye. In some embodiments, the promoter is a CRALBP or RPE65 promoter (e.g., a promoter having the nucleotide sequence of SEQ ID NO: 6 or 32). In some embodiments, the promoter is associated with strong expression in the liver. In some embodiments, the promoter is an AAT1, ALB or PCK1 promoter (e.g., a promoter having the nucleotide sequence of SEQ ID NO: 16, 18, or 20. In some embodiments, if the gene to be expressed in the AAV vector is CFH or CFHL (e.g., a gene comprising the nucleotide sequence of any one of SEQ ID NOs: 1-3 or 5, or a codon-optimized and/or fragment thereof), then the promoter is less than 1000, 900, 800, 700, 600, 500, 400 or 300 bp in size. In some embodiments, if the gene to be expressed in the AAV vector is CFH or CFHL (e.g., a gene comprising the nucleotide sequence of any one of SEQ ID NOs: 1-3 or 5, or a codon-optimized and/or fragment thereof), then the promoter is a promoter selected from the CRALBP, EF1a, HSP70 or sCBA promoter. In some embodiments, if the gene to be expressed in the AAV vector is CFH or CFHL (e.g., a gene comprising the nucleotide sequence of any one of SEQ ID NOs: 1-3 or 5, or a codon-optimized and/or fragment thereof), then the promoter comprises the nucleotide sequence of any one of SEQ ID NOs: 6, 8, 12, 14, 16, 18, 20, 31, 32, or 36 or codon-optimized and/or fragments thereof. In some embodiments, any of the promoters disclosed herein is coupled with a viral intron (e.g., an SV40i intron). 
     In another embodiment, the promoter is the native promoter for the gene to be expressed. Useful promoters include, without limitation, the rod opsin promoter, the red-green opsin promoter, the blue opsin promoter, the cGMP-β-phosphodiesterase promoter, the mouse opsin promoter (Beltran et al 2010 cited above), the rhodopsin promoter (Mussolino et al, Gene Ther, July 2011, 18(7):637-45); the alpha-subunit of cone transducin (Morrissey et al, BMC Dev, Biol, January 2011, 11:3); beta phosphodiesterase (PDE) promoter; the retinitis pigmentosa (RP1) promoter (Nicoud et al, J. Gene Med, December 2007, 9(12): 1015-23); the NXNL2/NXNL1 promoter (Lambard et al, PLoS One, October 2010, 5(10):e13025), the RPE65 promoter; the retinal degeneration slow/peripherin 2 (Rds/perph2) promoter (Cai et al, Exp Eye Res. 2010 August; 91(2): 186-94); and the VMD2 promoter (Kachi et al, Human Gene Therapy, 2009 (20:31-9)). Each of these documents is incorporated by reference herein. In one embodiment, the promoter is of a small size, under 1000 bp, due to the size limitations of the AAV vector. In another embodiment, the promoter is under 400 bp. 
     In certain embodiments, any promoters suitable for use in AAV vectors may be used with the vectors of the disclosure. Examples of suitable promoters include constitutive promoters such as a CMV promoter (optionally with the CMV enhancer), RSV promoter (optionally with the RSV enhancer), SV40 promoter, MoMLV promoter, CB promoter, the dihydrofolate reductase promoter, the chicken β-actin (CBA) promoter, CBA/CAG promoter, and the immediate early CMV enhancer coupled with the CBA promoter, or a EF1a promoter, etc. In some embodiments a cell- or tissue-specific promoter is utilized (e.g., a rod, cone, or ganglia derived promoter). In certain embodiments, the promoter is small enough to be compatible with the disclosed constructs, e.g., the CB promoter. Preferably, the promoter is a constitutive promoter. In another embodiment, the promoter is cell-specific. The term “cell-specific” means that the particular promoter selected for the recombinant vector can direct expression of the selected transgene in a particular ocular cell type. In one embodiment, the promoter is specific for expression of the transgene in photoreceptor cells. In another embodiment, the promoter is specific for expression in the rods and cones. In another embodiment, the promoter is specific for expression in the rods. In another embodiment, the promoter is specific for expression in the cones. In another embodiment, the promoter is specific for expression of the transgene in RPE cells. In another embodiment, the transgene is expressed in any of the above noted ocular cells. 
     Other useful promoters include transcription factor promoters including, without limitation, promoters for the neural retina leucine zipper (Nrl), photoreceptor-specific nuclear receptor Nr2e3, and basic-leucine zipper (bZIP). In one embodiment, the promoter is of a small size, under 1000 bp, due to the size limitations of the AAV vector. In another embodiment, the promoter is under 400 bp. 
     Other regulatory sequences useful herein include enhancer sequences Enhancer sequences useful herein include the IRBP enhancer (Nicoud 2007, cited above), immediate early cytomegalovirus enhancer, one derived from an immunoglobulin gene or SV40 enhancer, the cis-acting element identified in the mouse proximal promoter, etc. 
     Selection of these and other common vector and regulatory elements are conventional and many such sequences are available. See, e.g., Sambrook et al, and references cited therein at, for example, pages 3.18-3.26 and 16.17-16.27 and Ausubel et al., Current Protocols in Molecular Biology, John Wiley &amp; Sons, New York, 1989). It is understood that not all vectors and expression control sequences will function equally well to express all of the transgenes as described herein. However, one of skill in the art may make a selection among these, and other, expression control sequences to generate the rAAV vectors of the disclosure. 
     Production of rAAV Vectors 
     Numerous methods are known in the art for production of rAAV vectors, including transfection, stable cell line production, and infectious hybrid virus production systems which include adenovirus-AAV hybrids, herpesvirus-AAV hybrids (Conway, J E et al., (1997). Virology 71(11):8780-8789) and baculovirus-AAV hybrids. rAAV production cultures for the production of rAAV virus particles all require; 1) suitable host cells, including, for example, human-derived cell lines such as HeLa, A549, or 293 cells, or insect-derived cell lines such as SF-9, in the case of baculovirus production systems; 2) suitable helper virus function, provided by wild-type or mutant adenovirus (such as temperature sensitive adenovirus), herpes virus, baculovirus, or a plasmid construct providing helper functions; 3) AAV rep and cap genes and gene products; 4) a transgene (such as a transgene encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof) flanked by at least one AAV ITR sequence; and 5) suitable media and media components to support rAAV production. Suitable media known in the art may be used for the production of rAAV vectors. These media include, without limitation, media produced by Hyclone Laboratories and JRH including Modified Eagle Medium (MEM), Dulbecco&#39;s Modified Eagle Medium (DMEM), custom formulations such as those described in U.S. Pat. No. 6,566,118, and Sf-900 II SFM media as described in U.S. Pat. No. 6,723,551, each of which is incorporated herein by reference in its entirety, particularly with respect to custom media formulations for use in production of recombinant AAV vectors. 
     The rAAV particles can be produced using methods known in the art. See, e.g., U.S. Pat. Nos. 6,566,118; 6,989,264; and 6,995,006. In practicing the disclosure, host cells for producing rAAV particles include mammalian cells, insect cells, plant cells, microorganisms and yeast. Host cells can also be packaging cells in which the AAV rep and cap genes are stably maintained in the host cell or producer cells in which the AAV vector genome is stably maintained. Exemplary packaging and producer cells are derived from 293, A549 or HeLa cells. AAV vectors are purified and formulated using standard techniques known in the art. 
     Recombinant AAV particles are generated by transfecting producer cells with a plasmid (cis-plasmid) containing a rAAV genome comprising a transgene flanked by the 145 nucleotide-long AAV ITRs and a separate construct expressing the AAV rep and CAP genes in trans. In addition, adenovirus helper factors such as E1A, E1B, E2A, E4ORF6 and VA RNAs, etc. may be provided by either adenovirus infection or by transfecting a third plasmid providing adenovirus helper genes into the producer cells. Producer cells may be HEK293 cells. Packaging cell lines suitable for producing adeno-associated viral vectors may be readily accomplished given readily available techniques (see e.g., U.S. Pat. No. 5,872,005). The helper factors provided will vary depending on the producer cells used and whether the producer cells already carry some of these helper factors. 
     In some embodiments, rAAV particles may be produced by a triple transfection method, such as the exemplary triple transfection method provided infra. Briefly, a plasmid containing a rep gene and a capsid gene, along with a helper adenoviral plasmid, may be transfected (e.g., using the calcium phosphate method) into a cell line (e.g., HEK-293 cells), and virus may be collected and optionally purified. 
     In some embodiments, rAAV particles may be produced by a producer cell line method, such as the exemplary producer cell line method provided infra (see also (referenced in Martin et al., (2013) Human Gene Therapy Methods 24:253-269). Briefly, a cell line (e.g., a HeLa cell line) may be stably transfected with a plasmid containing a rep gene, a capsid gene, and a promoter-transgene sequence. Cell lines may be screened to select a lead clone for rAAV production, which may then be expanded to a production bioreactor and infected with an adenovirus (e.g., a wild-type adenovirus) as helper to initiate rAAV production. Virus may subsequently be harvested, adenovirus may be inactivated (e.g., by heat) and/or removed, and the rAAV particles may be purified. 
     In some aspects, a method is provided for producing any rAAV particle as disclosed herein comprising (a) culturing a host cell under a condition that rAAV particles are produced, wherein the host cell comprises (i) one or more AAV package genes, wherein each said AAV packaging gene encodes an AAV replication and/or encapsidation protein; (ii) a rAAV pro-vector comprising a nucleic acid encoding a therapeutic polypeptide and/or nucleic acid as described herein flanked by at least one AAV ITR, and (iii) an AAV helper function; and (b) recovering the rAAV particles produced by the host cell. In some embodiments, said at least one AAV ITR is selected from the group consisting of AAV ITRs are AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh8R, AAV9, AAV10, AAVrh10, AAV11, AAV 12, AAV2R471A, AAV DJ, a goat AAV, bovine AAV, or mouse AAV or the like. In some embodiments, the encapsidation protein is an AAV2 encapsidation protein. 
     Suitable rAAV production culture media of the present disclosure may be supplemented with serum or serum-derived recombinant proteins at a level of 0.5-20 (v/v or w/v). Alternatively, as is known in the art, rAAV vectors may be produced in serum-free conditions which may also be referred to as media with no animal-derived products. One of ordinary skill in the art may appreciate that commercial or custom media designed to support production of rAAV vectors may also be supplemented with one or more cell culture components know in the art, including without limitation glucose, vitamins, amino acids, and or growth factors, in order to increase the titer of rAAV in production cultures. 
     rAAV production cultures can be grown under a variety of conditions (over a wide temperature range, for varying lengths of time, and the like) suitable to the particular host cell being utilized. As is known in the art, rAAV production cultures include attachment-dependent cultures which can be cultured in suitable attachment-dependent vessels such as, for example, roller bottles, hollow fiber filters, microcarriers, and packed-bed or fluidized-bed bioreactors. rAAV vector production cultures may also include suspension-adapted host cells such as HeLa, 293, and SF-9 cells which can be cultured in a variety of ways including, for example, spinner flasks, stirred tank bioreactors, and disposable systems such as the Wave bag system. 
     rAAV vector particles of the disclosure may be harvested from rAAV production cultures by lysis of the host cells of the production culture or by harvest of the spent media from the production culture, provided the cells are cultured under conditions known in the art to cause release of rAAV particles into the media from intact cells, as described more fully in U.S. Pat. No. 6,566,118). Suitable methods of lysing cells are also known in the art and include for example multiple freeze/thaw cycles, sonication, microfluidization, and treatment with chemicals, such as detergents and/or proteases. 
     In a further embodiment, the rAAV particles are purified. The term “purified” as used herein includes a preparation of rAAV particles devoid of at least some of the other components that may also be present where the rAAV particles naturally occur or are initially prepared from. Thus, for example, isolated rAAV particles may be prepared using a purification technique to enrich it from a source mixture, such as a culture lysate or production culture supernatant. Enrichment can be measured in a variety of ways, such as, for example, by the proportion of DNase-resistant particles (DRPs) or genome copies (gc) present in a solution, or by infectivity, or it can be measured in relation to a second, potentially interfering substance present in the source mixture, such as contaminants, including production culture contaminants or in-process contaminants, including helper virus, media components, and the like. 
     In some embodiments, the rAAV production culture harvest is clarified to remove host cell debris. In some embodiments, the production culture harvest is clarified by filtration through a series of depth filters including, for example, a grade DOHC Millipore Millistak+HC Pod Filter, a grade A1HC Millipore Millistak+HC Pod Filter, and a 0.2μη Filter Opticap XL 10 Millipore Express SHC Hydrophilic Membrane filter. Clarification can also be achieved by a variety of other standard techniques known in the art, such as, centrifugation or filtration through any cellulose acetate filter of 0.2μη or greater pore size known in the art. 
     In some embodiments, the rAAV production culture harvest is further treated with Benzonase® to digest any high molecular weight DNA present in the production culture. In some embodiments, the Benzonase® digestion is performed under standard conditions known in the art including, for example, a final concentration of 1-2.5 units/ml of Benzonase® at a temperature ranging from ambient to 37° C. for a period of 30 minutes to several hours. 
     rAAV particles may be isolated or purified using one or more of the following purification steps: equilibrium centrifugation; flow-through anionic exchange filtration; tangential flow filtration (TFF) for concentrating the rAAV particles; rAAV capture by apatite chromatography; heat inactivation of helper virus; rAAV capture by hydrophobic interaction chromatography; buffer exchange by size exclusion chromatography (SEC); nanofiltration; and rAAV capture by anionic exchange chromatography, cationic exchange chromatography, or affinity chromatography. These steps may be used alone, in various combinations, or in different orders. In some embodiments, the method comprises all the steps in the order as described below. Methods to purify rAAV particles are found, for example, in Xiao et al., (1998) Journal of Virology 72:2224-2232; U.S. Pat. Nos. 6,989,264 and 8,137,948; and WO 2010/148143. 
     Pharmaceutical Compositions 
     Also provided herein are pharmaceutical compositions comprising an rAAV particle comprising a transgene encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof and/or therapeutic nucleic acid, and a pharmaceutically acceptable carrier. The pharmaceutical compositions may be suitable for any mode of administration described herein; for example, by intravitreal administration. 
     In some embodiments, the composition comprises a polypeptide (or a nucleic acid encoding a polypeptide) that processes (e.g., cleaves) the complement system polypeptide encoded by the transgene in the rAAV. However, in particular embodiments, the composition does not comprise a polypeptide (or a nucleic acid encoding a polypeptide) that processes (e.g., cleaves) the complement system polypeptide encoded by the transgene in the rAAV. 
     Gene therapy protocols for retinal diseases, such as LCA, retinitis pigmentosa, and age-related macular degeneration require the localized delivery of the vector to the cells in the retina. The cells that will be the treatment target in these diseases are either the photoreceptor cells in the retina or the cells of the RPE underlying the neurosensory retina. Delivering gene therapy vectors to these cells requires injection into the subretinal space between the retina and the RPE. In some embodiments, the disclosure provides methods to deliver rAAV gene therapy vectors encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof to cells of the retina. 
     In some embodiments, the pharmaceutical compositions comprising a rAAV described herein and a pharmaceutically acceptable carrier is suitable for administration to a human subject. Such carriers are well known in the art (see, e.g., Remington&#39;s Pharmaceutical Sciences, 15th Edition, pp. 1035-1038 and 1570-1580). In some embodiments, the pharmaceutical compositions comprising a rAAV described herein and a pharmaceutically acceptable carrier is suitable for ocular injection. In some embodiments, the pharmaceutical composition is suitable for intravitreal injection. In some embodiments, the pharmaceutical composition is suitable for subretinal delivery. Such pharmaceutically acceptable carriers can be sterile liquids, such as water and oil, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, and the like. Saline solutions and aqueous dextrose, polyethylene glycol (PEG) and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. The pharmaceutical composition may further comprise additional ingredients, for example preservatives, buffers, tonicity agents, antioxidants and stabilizers, nonionic wetting or clarifying agents, viscosity-increasing agents, and the like. The pharmaceutical compositions described herein can be packaged in single unit dosages or in multidosage forms. The compositions are generally formulated as sterile and substantially isotonic solution. 
     In one embodiment, the recombinant AAV containing the desired transgene encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof and constitutive or tissue or cell-specific promoter for use in the target ocular cells as detailed above is formulated into a pharmaceutical composition intended for subretinal or intravitreal injection. In some embodiments, the compositions disclosed herein targets cells of any one or more regions of the macula including, for example, the umbo, the foveolar, the foveal avascular zone, the fovea, the parafovea, or the perifovea. Such formulation involves the use of a pharmaceutically and/or physiologically acceptable vehicle or carrier, particularly one suitable for administration to the eye, e.g., by subretinal injection, such as buffered saline or other buffers, e.g., HEPES, to maintain pH at appropriate physiological levels, and, optionally, other medicinal agents, pharmaceutical agents, stabilizing agents, buffers, carriers, adjuvants, diluents, etc. For injection, the carrier will typically be a liquid. Exemplary physiologically acceptable carriers include sterile, pyrogen-free water and sterile, pyrogen-free, phosphate buffered saline. A variety of such known carriers are provided in U.S. Pat. No. 7,629,322, incorporated herein by reference. In one embodiment, the carrier is an isotonic sodium chloride solution. In another embodiment, the carrier is balanced salt solution. In one embodiment, the carrier includes tween. If the virus is to be stored long-term, it may be frozen in the presence of glycerol or Tween20. In another embodiment, the pharmaceutically acceptable carrier comprises a surfactant, such as perfluorooctane (Perfluoron liquid). 
     In certain embodiments of the methods described herein, the pharmaceutical composition described above is administered to the subject by subretinal injection. In other embodiments, the pharmaceutical composition is administered by intravitreal injection. Other forms of administration that may be useful in the methods described herein include, but are not limited to, direct delivery to a desired organ (e.g., the eye), oral, inhalation, intranasal, intratracheal, intravenous, intramuscular, subcutaneous, intradermal, and other parental routes of administration. Routes of administration may be combined, if desired. In certain embodiments, the pharmaceutical compositions of the disclosure are administered after administration of an initial loading dose of the complement system protein. 
     In some embodiments, any of the vectors/pharmaceutical compositions disclosed herein are administered to a patient such that they target glial cells, Muller cells, and/or retinal pigment epithelial cells. In some embodiments, the route of administration does not specifically target neurons. In some embodiments, the route of administration is chosen such that it reduces the risk of retinal detachment in the patient (e.g., intravitreal rather than subretinal administration). In some embodiments, intravitreal administration is chosen if the vector/composition is to be administered to an elderly adult (e.g., at least 60 years of age). In particular embodiments, any of the vectors/pharmaceutical compositions disclosed herein are administered to a subject intravitreally. Procedures for intravitreal injection are known in the art (see, e.g., Peyman, G. A., et al. (2009) Retina 29(7):875-912 and Fagan, X. J. and Al-Qureshi, S. (2013) Clin. Experiment. Ophthalmol. 41(5):500-7). Briefly, a subject for intravitreal injection may be prepared for the procedure by pupillary dilation, sterilization of the eye, and administration of anesthetic. Any suitable mydriatic agent known in the art may be used for pupillary dilation. Adequate pupillary dilation may be confirmed before treatment. Sterilization may be achieved by applying a sterilizing eye treatment, e.g., an iodide-containing solution such as Povidone-Iodine (BETADINE®). A similar solution may also be used to clean the eyelid, eyelashes, and any other nearby tissues {e.g., skin). Any suitable anesthetic may be used, such as lidocaine or proparacaine, at any suitable concentration. Anesthetic may be administered by any method known in the art, including without limitation topical drops, gels or jellies, and subconjuctival application of anesthetic. Prior to injection, a sterilized eyelid speculum may be used to clear the eyelashes from the area. The site of the injection may be marked with a syringe. The site of the injection may be chosen based on the lens of the patient. For example, the injection site may be 3-3.5 mm from the limus in pseudophakic or aphakic patients, and 3.5-4 mm from the limbus in phakic patients. The patient may look in a direction opposite the injection site. During injection, the needle may be inserted perpendicular to the sclera and pointed to the center of the eye. The needle may be inserted such that the tip ends in the vitreous, rather than the subretinal space. Any suitable volume known in the art for injection may be used. After injection, the eye may be treated with a sterilizing agent such as an antiobiotic. The eye may also be rinsed to remove excess sterilizing agent. 
     Furthermore, in certain embodiments it is desirable to perform non-invasive retinal imaging and functional studies to identify areas of specific ocular cells to be targeted for therapy. In these embodiments, clinical diagnostic tests are employed to determine the precise location(s) for one or more subretinal injection(s). These tests may include ophthalmoscopy, electroretinography (ERG) (particularly the b-wave measurement), perimetry, topographical mapping of the layers of the retina and measurement of the thickness of its layers by means of confocal scanning laser ophthalmoscopy (cSLO) and optical coherence tomography (OCT), topographical mapping of cone density via adaptive optics (AO), functional eye exam, etc. 
     These, and other desirable tests, are described in International Patent Application No. PCT/US2013/022628. In view of the imaging and functional studies, in some embodiments, one or more injections are performed in the same eye in order to target different areas of retained bipolar cells. The volume and viral titer of each injection is determined individually, as further described below, and may be the same or different from other injections performed in the same, or contralateral, eye. In another embodiment, a single, larger volume injection is made in order to treat the entire eye. In one embodiment, the volume and concentration of the rAAV composition is selected so that only a specific region of ocular cells is impacted. In another embodiment, the volume and/or concentration of the rAAV composition is a greater amount, in order reach larger portions of the eye, including non-damaged ocular cells. 
     The composition may be delivered in a volume of from about 0.1 μL to about 1 mL, including all numbers within the range, depending on the size of the area to be treated, the viral titer used, the route of administration, and the desired effect of the method. In one embodiment, the volume is about 50 μL. In another embodiment, the volume is about 70 μL. In a preferred embodiment, the volume is about 100 μL. In another embodiment, the volume is about 125 μL. In another embodiment, the volume is about 150 μL. In another embodiment, the volume is about 175 μL. In yet another embodiment, the volume is about 200 μL. In another embodiment, the volume is about 250 μL. In another embodiment, the volume is about 300 μL. In another embodiment, the volume is about 450 μL. In another embodiment, the volume is about 500 μL. In another embodiment, the volume is about 600 μL. In another embodiment, the volume is about 750 μL. In another embodiment, the volume is about 850 μL. In another embodiment, the volume is about 1000 μL. An effective concentration of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the desired transgene under the control of the cell-specific promoter sequence desirably ranges from about 10 7  and 10 13  vector genomes per milliliter (vg/mL) (also called genome copies/mL (GC/mL)). The rAAV infectious units are measured as described in S. K. McLaughlin et al, 1988 J. Virol., 62: 1963, which is incorporated herein by reference. Preferably, the concentration in the retina is from about 1.5×10 9  vg/mL to about 1.5×10 12  vg/mL, and more preferably from about 1.5×10 9  vg/mL to about 1.5×10 11  vg/mL. In certain preferred embodiments, the effective concentration is about 2.5×10 10  vg to about 1.4×10 11 . In one embodiment, the effective concentration is about 1.4×10 8  vg/mL. In one embodiment, the effective concentration is about 3.5×10 10  vg/mL. In another embodiment, the effective concentration is about 5.6×10 11  vg/mL. In another embodiment, the effective concentration is about 5.3×10 12  vg/mL. In yet another embodiment, the effective concentration is about 1.5×10 12  vg/mL. In another embodiment, the effective concentration is about 1.5×10 13  vg/mL. In one embodiment, the effective dosage (total genome copies delivered) is from about 10 7  to 10 13  vector genomes. It is desirable that the lowest effective concentration of virus be utilized in order to reduce the risk of undesirable effects, such as toxicity, retinal dysplasia and detachment. Still other dosages and administration volumes in these ranges may be selected by the attending physician, taking into account the physical state of the subject, preferably human, being treated, the age of the subject, the particular ocular disorder and the degree to which the disorder, if progressive, has developed. For extra-ocular delivery, the dosage will be increased according to the scale-up from the retina. Intravenous delivery, for example may require doses on the order of 1.5×10 13  vg/kg. 
     Pharmaceutical compositions useful in the methods of the disclosure are further described in PCT publication No. WO2015168666 and PCT publication no. WO2014011210, the contents of which are incorporated by reference herein. 
     Methods of Treatment/Prophylaxis 
     Described herein are various methods of preventing, treating, arresting progression of or ameliorating the ocular disorders and retinal changes associated therewith. Generally, the methods include administering to a mammalian subject in need thereof, an effective amount of a composition comprising a recombinant adeno-associated virus (AAV) described above, carrying a transgene encoding a complement system polypeptide (e.g. CFH, FHL1, FHR1, FHR2, FHR3, FHR4, or FHR5) or a biologically active fragment thereof under the control of regulatory sequences which express the product of the gene in the subject&#39;s ocular cells, and a pharmaceutically acceptable carrier. Any of the AAV described herein are useful in the methods described below. 
     Gene therapy protocols for retinal diseases, such as LCA, retinitis pigmentosa, and age-related macular degeneration require the localized delivery of the vector to the cells in the retina. The cells that will be the treatment target in these diseases are either the photoreceptor cells in the retina or the cells of the RPE underlying the neurosensory retina. Delivering gene therapy vectors to these cells requires injection into the subretinal space between the retina and the RPE. In some embodiments, the disclosure provides methods to deliver rAAV gene therapy vectors comprising a complement system gene or a fragment thereof to cells of the retina. 
     In a certain aspect, the disclosure provides a method of treating a subject having age-related macular degeneration (AMD), comprising the step of administering to the subject any of the vectors of the disclosure. In certain embodiments, the vectors are administered at a dose between 2.5×10 10  vg and 1.4×10 11  vg/per eye in about 50 μl to about 100 μl. In certain embodiments, the vectors are administered at a dose between 1.0×10 11  vg and 1.5×10 13  vg/per eye in about 50 μl to about 100 In certain embodiments, the vectors are administered at a dose between 1.0×10 11  vg and 1.5×10 12  vg/per eye in about 50 μl to about 100 In certain embodiments, the vectors are administered at a dose of about 1.4×10 12  vg/per eye in about 50 μl to about 100 In certain embodiments, the vectors are administered at a dose of 1.4×10 12  vg/per eye in about 50 μl to about 100 In certain embodiments, the pharmaceutical compositions of the disclosure comprise a pharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical compositions of the disclosure comprise PBS. In certain embodiments, the pharmaceutical compositions of the disclosure comprise pluronic. In certain embodiments, the pharmaceutical compositions of the disclosure comprise PBS, NaCl and pluronic. In certain embodiments, the vectors are administered by intravitreal injection in a solution of PBS with additional NaCl and pluronic. 
     In some embodiments, any of the vectors of the present disclosure used according to the methods disclosed herein is capable of inducing at least 5%, 10%, 20%, 50%, 100%, 150%, 200%, 250%, 300%, 400%, 500%, 700%, 900%, 1000%, 1100%, 1500%, or 2000% higher expression of CFH and/or FHL1 in a target cell disclosed herein (e.g., an RPE or liver cell) as compared to the endogenous expression of CFH and/or FHL1 in the target cell. In some embodiments, expression of any of the vectors disclosed herein in a target cell disclosed herein (e.g., an RPE or liver cell) results in at least 5%, 10%, 20%, 50%, 100%, 150%, 200%, 250%, 300%, 400%, 500%, 700%, 900%, 1000%, 1100%, 1500%, or 2000% higher levels of CFH and/or FHL1 activity in the target cell as compared to endogenous levels of CFH and/or FHL1 activity in the target cell. 
     In some embodiments, any of the vectors disclosed herein is administered to cell(s) or tissue(s) in a test subject. In some embodiments, the cell(s) or tissue(s) in the test subject express less CFH and/or FHL1, or less functional CFH and/or FHL1, than expressed in the same cell type or tissue type in a reference control subject or population of reference control subjects. In some embodiments, the reference control subject is of the same age and/or sex as the test subject. In some embodiments, the reference control subject is a healthy subject, e.g., the subject does not have a disease or disorder of the eye. In some embodiments, the reference control subject does not have a disease or disorder of the eye associated with activation of the complement cascade. In some embodiments, the reference control subject does not have macular degeneration. In some embodiments, the eye and/or a specific cell type of the eye (e.g., cells in the foveal region) in the test subject express at least 95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, or 1% less CFH and/or FHL1 or functional CFH and/or FHL1 as compared to the levels in the reference control subject or population of reference control subjects. In some embodiments, a the eye or a specific cell type of the eye (e.g., cells in the foveal region) in the test subject express CFH and/or FHL1 protein having any of the CFH and/or FHL1 mutations disclosed herein. In some embodiments, the eye or a specific cell type of the eye (e.g., cells in the foveal region) in the reference control subject do not express a CFH and/or FHL1 protein having any of the CFH and/or FHL1 mutations disclosed herein. In some embodiments, expression of any of the vectors disclosed herein in the cell(s) or tissue(s) of the test subject results in an increase in levels of CFH and/or FHL1 protein or functional CFH and/or FHL1 protein. In some embodiments, expression of any of the vectors disclosed herein in the cell(s) or tissue(s) of the test subject results in an increase in levels of CFH and/or FHL1 protein or functional CFH and/or FHL1 protein such that the increased levels are within 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, or 1% of, or are the same as, the levels of CFH and/or FHL1 protein or functional CFH and/or FHL1 protein expressed by the same cell type or tissue type in the reference control subject or population of reference control subjects. In some embodiments, expression of any of the vectors disclosed herein in the cell(s) or tissue(s) of the test subject results in an increase in levels of CFH and/or FHL1 protein or functional CFH and/or FHL1 protein, but the increased levels of CFH and/or FHL1 protein or functional CFH and/or FHL1 protein do not exceed the levels of CFH and/or FHL1 protein or functional CFH and/or FHL1 protein expressed by the same cell type or tissue type in the reference control subject or population of reference control subjects. In some embodiments, expression of any of the vectors disclosed herein in the cell(s) or tissue(s) of the test subject results in an increase in levels of CFH and/or FHL1 protein or functional CFH and/or FHL1 protein, but the increased levels of CFH and/or FHL1 protein or functional CFH and/or FHL1 protein exceed the levels of CFH and/or FHL1 protein or functional CFH and/or FHL1 protein by no more than 1%, 5%, 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 100% of the levels expressed by the same cell type or tissue type in the reference control subject or population of reference control subjects. In some embodiments, any of the treatment and/or prophylactic methods disclosed herein are applied to a subject. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the human is an adult. In some embodiments, the human is an elderly adult. In some embodiments, the human is at least 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 years of age. In particular embodiments, the human is at least 60 or 65 years of age. 
     In some embodiments, any of the treatment and/or prophylactic methods disclosed herein is for use in treatment of a patient having one or more mutations that causes amacular degeneration (AMD) or that increases the likelihood that a patient develops AMD. In some embodiments, any of the treatment and/or prophylactic methods disclosed herein is for use in treatment of a patient having one or more mutations that causes atypical hemolytic uremic syndrome (aHUS) or that increases the likelihood that a patient develops aHUS. In some embodiments, the one or more mutations are in the patient&#39;s CFI gene. In some embodiments, the one or more mutations are in the patient&#39;s CFH gene. In some embodiments, the one or more mutations are in both the patient&#39;s CFH and CFI genes. In some embodiments, the subject has a loss-of-function mutation in the subject&#39;s CFH gene. In some embodiments, the subject has a loss-of-function mutation in the subject&#39;s CFI gene. 
     In some embodiments, any of the treatment and/or prophylactic methods disclosed herein is for use in treatment of a patient having one or more mutations in the patient&#39;s CFI gene. In some embodiments, the patient has a mutation in one or more of the FIMAC, CD5, L1, L1-Ca binding, L1-disulfid bond, L2, L2-Ca binding, serine protease, or serine protease active site domains. In some embodiments, the patient has one or more mutations in the disulphide bond sites in the CFI protein. In some embodiments, the mutation is one or more of the mutations selected from the group consisting of: E548Q, V412M, A431T, A431S, K441R, P553S, A240G, A258T, G119R, G261D, R2021, T300A, T2031, V152M, R317W, G287R, E554V, 1340T, G162D, P50A, Y206N, D310E, H418L, p.(Tyr411Stop), p.(Arg187Stop), R474Q, Y459S, R187Q, R339Q, G263V, p.(Arg339Stop), D477H, p.(Ile357Met), P64L, E109A, G125R, N1771, F198L, S221Y, D224N, C229R, V230M, G248E, G280D, A356P, V201, Y369S, W374C, R389H, W399R, C467R, G487C, I492L, G500R, R502C, W541*, V543A, Q580*, V355M, I578T, R474*, R406H, D44N, p.(Arg406Cys), D403N, 1416L, G328R, G512S, p.(Gly542Ser), p.(Cys106Arg), V127A, p.(Ile55Phe), H40R, C54R, C54*, V184M, G362A, Q462H, N536K, R317Q, p.(His 183Arg), p.(Ile306Val), p.(Gly342Glu), p.(Asp429Glu), R448H, D519N, S493R, R448C, K338Q, G104R, C259R, G372S, A360V, E290A, V213F, F13V, Y514Ter, V396A, E303Q, H401Q, 1306T, E479G, c.772+1G&gt;T, F498L, Y411H, S24T, C255Y, R168S, Q228R, V4691, Q250K, Y241C, G232V, G248R, G110R, E109K, N422D, C550R, G242AfsTer9, R345G, N428MfsTer5, C550WfsTer17, V341E, N428S, H334P, W51R, A452S, T72S, T72S, V5581, E445G, C444Y, L3511, G261S, M1381, A563S, G263AfsTer37, K142E, c.658+2T&gt;C, G205D, T197A, G188V, A378V, L376P, C365Y, M147V, Q161Ter, G439R, G269S, R201S, P576S, Y65H, c.907+1G&gt;Aâ€, Y22C, 1407T, M204V, A384T, G516V, R336G, F139V, L4H, K117E, V4891, P402L, G547R, A346T, S326P, I126T, D283G, S298F, loss of Metl, Ter584QextTer24, C521Y, R168G, S457P, A423E, L34V, A452T, K442E, N245K, D173N, K267E, S146R, E302K, G295V, V299L, K111N, S113N, F17V, Q391E, H14L, T3941, c.659-2A&gt;G, A511V, E303K, D398G, Ter584KextTer24, V583A, A163T, H118Q, A309S, T231, G473R, V5301, E26Ter, K497N, S496C, S496T, L491R, V412E, F417S, S570G, D465G, E124K, D567V, G557D, E548G, W546G, V5431, N464K, P463A, N564S, K561E, E445D, C444G, D443H, E434KfsTer2, 1430T, I244S, I244V, c328+1G&gt;A, R345Q, S175F, N331KfsTer46, C327R, K1301, Q260E, P96S, 1140T, T1371, D135G, K69E, G57D, G371V, G367A, N279S, Y276C, G269C, E190D, T300A, G261D, N151S, R406H, V152M, G362A, E554V, S570T, 1340T, K441R, T2031, Y206N, G328R, T107A, P553S, G287R, N70T, P50A, R406C, R187Q, G119R, 0.1429+1G&gt;C, D477H, N1771, V129A, I55V, W399R, G500R, I492L, R339Ter, I357M, R474Q, D44N, D403N, R474Ter, R317W, G512S, R339Q, A356P, R187Ter, 1416L, R317L, R389H, 1306V, D224Y, R317Q, A258T, Q580Tet, H418L, I578T, G542S, P64L, C106R, Y369S, Q462H, A240G, H183R, R502G, H40R or G162D. In particular embodiments, the mutation is any one of the mutations selected from the group consisting of: G119R, L131R, V152M, G162D, R187Y, R187T, T2031, A240G, A258T, G287R, A300T, R317W, R339Q, V412M, and P553S. In some embodiments, any of the CFI mutant amino acid positions described herein correspond to the wildtype amino acid CFI sequence of SEQ ID NO: 35. 
     In some embodiments, any of the treatment and/or prophylactic methods disclosed herein is for use in treatment of a patient having one or more mutations in the patient&#39;s CFH gene. In some embodiments, the patient has a mutation in one or more of the pre-SCR1 or any of the SCR1-SCR20 domains. In some embodiments, the patient has a mutation in one or more of the transition regions between SCRs. In some embodiments, the mutation is one or more of the mutations selected from the group consisting of: H402Y, G69E, D194N, W314C, A806T, Q950H, p. I1e184fsX, p.Lys204fsX, c.1697-17_-8del, A161S, A173G, R175Q, V62I, V1007L, S890I, S193L, I216T, A301Nfs*25, W379R, Q400K, Q950H, T956M, R1210C, N1050Y, E936D, Q408X, R1078S, c.350+6T-&gt;G, R567G, R53C, R53H, R2T, A892V, R567G, I221V, S159N, P562H, F960S, R303W, R303Q, K666N, G1194D, P258L, G650V, D130N, S58A, R166W, R232Q, R127H, K1202N, G397Stop, Stop450R, R830W, I622L, T732M, S884Y, L24V, Y235H, K527N, R582H, C973Y, V1089M, E123G, T291S, R567K, E625Stop, N802S, N1056K, R1203W, Q1076E, P26S, T46A, T91S, C129Y, R166Q, E167Q, R175P, C192F, W198*, V206M, G218*, M239T, Y277*, C325Y, R341H, R364L, P384R, C431S, D454A, A473V, P503A, N516K, I551T, H699R, F717L, W978R, P981S, A1010V, W1037*, P1051L, I1059T, Q1143E, R1206H, T12271, L24V, H169R, R257H, K410E, V6091, D619N, A892V, G1002R, G278S, T30*, I32Stop, R78G, Q81P, V111E, W134R, P139S, M162V, E189Stop, K224Del, K224Del, A307A, H332Y, S411T, C448Y, L479Stop, R518T, T519A, C536R, C564P, C569Stop, L578Stop, P621T, C623S, C630W, E635D, K670T, Q672Q, C673Y, C673S, S714Stop, S722*, C733Y, V737V, E762Stop, N774Stop, R7801, G786*, M823T, V835L, E847V, E850K, C853R, C853T, C864S, C870R, H878H, I881L, E889Stop, H893R, Y899Stop, Y899D, C915S, C915Stop, W920R, Q925Stop, C926F, Y951H, C959Y, P968*, 1970V, T987A, N997T, G1011*, T10171, Y1021F, C1043R, T1046T, V1054I, V1060A, V1060L, C1077W, T1097W, T1097T, D1119G, D1119N, P1130L, V1134G, E1135R, E1137L, E1139Stop, Y1142D, Y1142C, C1152S, W1157R, P1161T, C1163T, P1166L, V1168E, V1168Stop, I1169L, E1172Stop, Y1177C, R1182S, W1183L, W1183R, W1183L, W1183Stop, W1183C, T1184R, T1184A, K1186H, K1188Del, L1189R, L1189F, S1191L, S1191W, E1195Stop, V1197A, E1198A, E1198Stop, F1199S, V1200L, G1204E, L1207R, S1211P, R1215Q, R1215G, T1216Del, C1218R, Y1225*, P1226S, L3V, H821Y, E954del, G255E, T1038R, V383A, V641A, P213A, I221V, E229K, R2T, R1072G, G967E, N819S, V579F, G19K, A18S, K834E, 1504M, R6621, P668L, G133R, I184T, L697F, H1165Y, G1110A, pI1e808_Gln809del, I760L, T447R, I808M, I868M, L765F, N767S, R567G, K768N, S209L, Q628K, D214Y, N401D, I216K, Q464R, I777V, E229D, M8231, R232Ter, S266L, P260S, E23G, C80Y, R781, R582H, N638D, N638S, P258L, L3F, R257H, G240R, G69R, D855N, M111, K472N, Q840H, E850K, Y899H, T645M, M805V, K919T, E201G, V407A, 1907L, T914K, H332R, V144M, S652G, D195N, C146S, P661R, E677Q, V482I, I34R, A421T, R281G, C509Y, K666N, P440S, C442G, N607D, A425V, G667E, P440L, I49V, R387G, E625K, E625Ter, T135S, P43S, K283E, I124V, T36V, 15631, G350E, D619G, T321I, T286A, P384L, T739N, M515L, V158A, G727R, T724K, F717L, M162V, C178R, G700R, A161T, F176L, R295S, F298Y, G297S, P300L, R1040K, V552L, T310I, T531A, G928D, Ter386RextTer 69â€, Q1143K, Y534C, P981L, K308N, D538E, R1215Ter, E105V, T10171, N10501, P935S, Y951H, T1097M, D947H, E961D, G962S, G964E, 1970V, R1072T, P1114L, S1122T, F960C, R1074C, R1182T, R1074L, S884Y, S890T, V8371, V941F, V1581, D748V, I216T, H371N, L750F, P418T, M432V, D693N, A746E, V111E, c.2237-2A&gt;G, P982S, V579A, E591D, V5791, V651, P418S, Y1067C, D772N, V72L, E189K, A1027P, D798N, N61D, P384S, N521S, P1068S, E395K, N774S, H577R, E833K, K6E, H337R, R444C, L741F, Y42F, D288E, S705F, R1040G, D214H, N757D, I861M, G848E, P923S, E201K, E902A, R303Q, G366E, D538H, K82R, E721K, Y1008H, R1074P, A806S, Q807R, C389Y, H764Y, K867N, P392T, L394M, E456K, F459L, Y398C, E570K, D214N, I574V, I574T, G631C, T8801, V865F, V576A, N776S, P633S, N22D, P634A, N8221, R885S, R232L, E635D, R778K, L827V, C267R, Y779C, R582C, L77S, R257C, Y327H, N75K, L74F, S836T, Y243H, c.1519+5_1519+8delGT . . . , K507Q, A892S, I15T, P924L, A14V, N842K, G894R, G894E, Y271C, C9W, T504R, V683M, L385Pheâ€, S898R, Q408H, G409S, T34K, E648G, I412V, E338D, P799S, G480E, D798E, D195Y, R341C, D485H, D485G, K598Q, Y420H, P599T, N434H, R441T, C431G, V149A, V3491, T679A, P43T, G45D, R662G, T5191, L121P, P364L, P621A, H373Y, D538MfsTer14, H371P, T544A, T131A, R166G, V1771, V177A, R729S, F717V, N718S, S991G, L981, Y1016Ter, T1217del, M1001T, K1004E, A1010T, G1011D, T1017A, T1031A, L1125F, R1203G, L1214M, W1096DfsTer20, H939N F960L, D966H, M10641, E1071K, N1095K, T1106A, G1107E, C1109W, P1111S, V11971, Y1075F, S1079N, P1080S, E1082G, or Sto1232. In particular embodiments, the mutation is one or more of the mutations selected from the group consisting of: R2T, L3V, R53C, R53H, S58A, G69E, D90G, R175Q, S193L, I216T, 1221V, R303W, H402Y, Q408X, P503A, G650V, R1078S, and R1210C. In some embodiments, any of the CFH mutant amino acid positions described herein correspond to the wildtype amino acid CFH sequence of SEQ ID NO: 33. 
     In some embodiments, any of the vectors disclosed herein are for use in treating a renal disease or complication. In some embodiments, the renal disease or complication is associated with AMD in the patient. In some embodiments, the renal disease or complication is associated with aHUS in the patient. In some embodiments, the vector administered for treating a renal disease or complication comprises a promoter that is associated with strong expression in the liver. In some embodiments, the promoter is an AAT1, PCK1, or ALB1 promoter (e.g., a promoter comprising the nucleotide sequence of any one of SEQ ID Nos: 16, 18 or 20). 
     The retinal diseases described above are associated with various retinal changes. These may include a loss of photoreceptor structure or function; thinning or thickening of the outer nuclear layer (ONL); thinning or thickening of the outer plexiform layer (OPL); disorganization followed by loss of rod and cone outer segments; shortening of the rod and cone inner segments; retraction of bipolar cell dendrites; thinning or thickening of the inner retinal layers including inner nuclear layer, inner plexiform layer, ganglion cell layer and nerve fiber layer; opsin mislocalization; overexpression of neurofilaments; thinning of specific portions of the retina (such as the fovea or macula); loss of ERG function; loss of visual acuity and contrast sensitivity; loss of optokinetic reflexes; loss of the pupillary light reflex; and loss of visually guided behavior. In one embodiment, a method of preventing, arresting progression of or ameliorating any of the retinal changes associated with these retinal diseases is provided. As a result, the subject&#39;s vision is improved, or vision loss is arrested and/or ameliorated. 
     In a particular embodiment, a method of preventing, arresting progression of or ameliorating vision loss associated with an ocular disorder in the subject is provided. Vision loss associated with an ocular disorder refers to any decrease in peripheral vision, central (reading) vision, night vision, day vision, loss of color perception, loss of contrast sensitivity, or reduction in visual acuity. 
     In another embodiment, a method of targeting one or more type(s) of ocular cells for gene augmentation therapy in a subject in need thereof is provided. In another embodiment, a method of targeting one or more type of ocular cells for gene suppression therapy in a subject in need thereof is provided. In yet another embodiment, a method of targeting one or more type of ocular cells for gene knockdown/augmentation therapy in a subject in need thereof is provided. In another embodiment, a method of targeting one or more type of ocular cells for gene correction therapy in a subject in need thereof is provided. In still another embodiment, a method of targeting one or more type of ocular cells for neurotropic factor gene therapy in a subject in need thereof is provided. 
     In any of the methods described herein, the targeted cell may be an ocular cell. In one embodiment, the targeted cell is a glial cell. In one embodiment, the targeted cell is an RPE cell. In another embodiment, the targeted cell is a photoreceptor. In another embodiment, the photoreceptor is a cone cell. In another embodiment, the targeted cell is a Muller cell. In another embodiment, the targeted cell is a bipolar cell. In yet another embodiment, the targeted cell is a horizontal cell. In another embodiment, the targeted cell is an amacrine cell. In still another embodiment, the targeted cell is a ganglion cell. In still another embodiment, the gene may be expressed and delivered to an intracellular organelle, such as a mitochondrion or a lysosome. 
     As used herein “photoreceptor function loss” means a decrease in photoreceptor function as compared to a normal, non-diseased eye or the same eye at an earlier time point. As used herein, “increase photoreceptor function” means to improve the function of the photoreceptors or increase the number or percentage of functional photoreceptors as compared to a diseased eye (having the same ocular disease), the same eye at an earlier time point, a non-treated portion of the same eye, or the contralateral eye of the same patient. Photoreceptor function may be assessed using the functional studies described above and in the examples below, e.g., ERG or perimetry, which are conventional in the art. 
     For each of the described methods, the treatment may be used to prevent the occurrence of retinal damage or to rescue eyes having mild or advanced disease. As used herein, the term “rescue” means to prevent progression of the disease to total blindness, prevent spread of damage to uninjured ocular cells, improve damage in injured ocular cells, or to provide enhanced vision. In one embodiment, the composition is administered before the disease becomes symptomatic or prior to photoreceptor loss. By symptomatic is meant onset of any of the various retinal changes described above or vision loss. In another embodiment, the composition is administered after disease becomes symptomatic. In yet another embodiment, the composition is administered after initiation of photoreceptor loss. In another embodiment, the composition is administered after outer nuclear layer (ONL) degeneration begins. In some embodiments, it is desirable that the composition is administered while bipolar cell circuitry to ganglion cells and optic nerve remains intact. 
     In another embodiment, the composition is administered after initiation of photoreceptor loss. In yet another embodiment, the composition is administered when less than 90% of the photoreceptors are functioning or remaining, as compared to a non-diseased eye. In another embodiment, the composition is administered when less than 80% of the photoreceptors are functioning or remaining. In another embodiment, the composition is administered when less than 70% of the photoreceptors are functioning or remaining. In another embodiment, the composition is administered when less than 60% of the photoreceptors are functioning or remaining. In another embodiment, the composition is administered when less than 50% of the photoreceptors are functioning or remaining. In another embodiment, the composition is administered when less than 40% of the photoreceptors are functioning or remaining. In another embodiment, the composition is administered when less than 30% of the photoreceptors are functioning or remaining. In another embodiment, the composition is administered when less than 20% of the photoreceptors are functioning or remaining. In another embodiment, the composition is administered when less than 10% of the photoreceptors are functioning or remaining. In one embodiment, the composition is administered only to one or more regions of the eye. In another embodiment, the composition is administered to the entire eye. 
     In another embodiment, the method includes performing functional and imaging studies to determine the efficacy of the treatment. These studies include ERG and in vivo retinal imaging, as described in the examples below. In addition visual field studies, perimetry and microperimetry, pupillometry, mobility testing, visual acuity, contrast sensitivity, color vision testing may be performed. 
     In yet another embodiment, any of the above described methods is performed in combination with another, or secondary, therapy. The therapy may be any now known, or as yet unknown, therapy which helps prevent, arrest or ameliorate any of the described retinal changes and/or vision loss. In one embodiment, the secondary therapy is encapsulated cell therapy (such as that delivering Ciliary Neurotrophic Factor (CNTF)). See, Sieving, P. A. et al, 2006. Proc Natl Acad Sci USA, 103(10):3896-3901, which is hereby incorporated by reference. In another embodiment, the secondary therapy is a neurotrophic factor therapy (such as pigment epithelium-derived factor, PEDF; ciliary neurotrophic factor 3; rod-derived cone viability factor (RdCVF) or glial-derived neurotrophic factor). In another embodiment, the secondary therapy is anti-apoptosis therapy (such as that delivering X-linked inhibitor of apoptosis, XIAP). In yet another embodiment, the secondary therapy is rod derived cone viability factor 2. The secondary therapy can be administered before, concurrent with, or after administration of the rAAV described above. 
     In some embodiments, any of the vectors or compositions disclosed herein is administered to a subject in combination with any of the other vectors or compositions disclosed herein. In some embodiments, any of the vectors or compositions disclosed herein is administered to a subject in combination with another therapeutic agent or therapeutic procedure. In some embodiments, the additional therapeutic agent is an anti-VEGF therapeutic agent (e.g., such as an anti-VEGF antibody or fragment thereof such as ranibizumab, bevacizumab or aflibercept), a vitamin or mineral (e.g., vitamin C, vitamin E, lutein, zeaxanthin, zinc or copper), omega-3 fatty acids, and/or Visudyne™. In some embodiments, the other therapeutic procedure is a diet having reduced omega-6 fatty acids, laser surgery, laser photocoagulation, submacular surgery, retinal translocation, and/or photodynamic therapy. 
     In some embodiments, any of the vectors disclosed herein is administered to a subject in combination with an additional agent needed for processing and/or improving the function of the protein encoded by the vector/composition. For example, if the vector comprises a CFH gene, the vector may be administered to a patient in combination with an antibody (or a vector encoding that antibody) that potentiates the activity of the expressed CFH protein. Examples of such antibodies are found in WO2016/028150, which is incorporated herein in its entirety. In some embodiments, the vector is administered in combination with an additional polypeptide (or a vector encoding that additional polypeptide), wherein the additional polypeptide is capable of processing the protein encoded by the vector, e.g., processing an encoded precursor protein into its mature form. In some embodiments, the processing protein is a protease (e.g., a furin protease). 
     Kits 
     In some embodiments, any of the vectors disclosed herein is assembled into a pharmaceutical or diagnostic or research kit to facilitate their use in therapeutic, diagnostic or research applications. A kit may include one or more containers housing any of the vectors disclosed herein and instructions for use. 
     The kit may be designed to facilitate use of the methods described herein by researchers and can take many forms. Each of the compositions of the kit, where applicable, may be provided in liquid form (e.g., in solution), or in solid form, (e.g., a dry powder). In certain cases, some of the compositions may be constitutable or otherwise processable (e.g., to an active form), for example, by the addition of a suitable solvent or other species (for example, water or a cell culture medium), which may or may not be provided with the kit. As used herein, “instructions” can define a component of instruction and/or promotion, and typically involve written instructions on or associated with packaging of the disclosure. Instructions also can include any oral or electronic instructions provided in any manner such that a user will clearly recognize that the instructions are to be associated with the kit, for example, audiovisual (e.g., videotape, DVD, etc.), Internet, and/or web-based communications, etc. The written instructions may be in a form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which instructions can also reflects approval by the agency of manufacture, use or sale for animal administration. 
     EXAMPLES 
     The disclosure now being generally described, it will be more readily understood by reference to the following examples, which are included merely for purposes of illustration of certain embodiments and embodiments of the present disclosure, and are not intended to limit the disclosure. 
     Example 1: Construction of AAV Vectors 
     AAV2 vectors were designed comprising either codon-optimized or non-codon-optimized CFH and/or CFHL sequences in combination with a variety of different promoters and, in some cases, SV40 introns.  FIGS. 1-6  show vector maps of the different vectors generated. A table is provided below outlining the gene included in the cassette, the promoter included, the Figure laying out the construct map, and the sequence associated with the vector. 
     
       
         
           
               
               
               
               
               
             
               
                   
               
               
                   
                   
                   
                   
                 Construct 
               
               
                 Construct Name 
                 Transgene 
                 Promoter 
                 Figure 
                 Sequence 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 pAAV-CRALBP- 
                 CFH 
                 CRALBP 
                 1 
                 7 
               
               
                 CFH 
                   
                   
                   
                   
               
               
                 pAAV-EF1a-CFH 
                 CFH 
                 EF1a 
                 2 
                 9 
               
               
                 pAAV-EF1a- 
                 CFH 
                 EF1a 
                 3 
                 11 
               
               
                 SV40i-CFH 
                   
                   
                   
                   
               
               
                 pAAV-HSP70- 
                 CFH 
                 HSP70 
                 4 
                 13 
               
               
                 CFH 
                   
                   
                   
                   
               
               
                 pAAV-sCBA-CFH 
                 CFH 
                 CBA 
                 5 
                 15 
               
               
                 pAAV-AAT1-CFH 
                 CFH 
                 AAT1 
                 6 
                 17 
               
               
                 pAAV-ALB-CFH 
                 CFH 
                 ALB 
                 7 
                 19 
               
               
                 pAAV-PCK1-CFH 
                 CFH 
                 PCK1 
                 8 
                 21 
               
               
                 pAAV-EF1a- 
                 CFHL 
                 EF1a 
                 9 
                 22 
               
               
                 CFHL 
                   
                   
                   
                   
               
               
                 pAAV-ALB-CFHL 
                 CFHL 
                 ALB 
                 10 
                 23 
               
               
                 pAAV-AAT1- 
                 CFHL 
                 AAT1 
                 11 
                 24 
               
               
                 CFHL 
                   
                   
                   
                   
               
               
                 pAAV-EF1a- 
                 CFHL 
                 EF1a 
                 12 
                 25 
               
               
                 SV40i-CFHL 
                   
                   
                   
                   
               
               
                 pAAV-CAG- 
                 CFHL 
                 CAG 
                 13 
                 26 
               
               
                 CFHL 
                   
                   
                   
                   
               
               
                 pAAV-CRALBP- 
                 CFHL 
                 CRALBP 
                 14 
                 27 
               
               
                 CFHL 
                   
                   
                   
                   
               
               
                 pAAV-hRPE65- 
                 CFHL 
                 hRPE65 
                 15 
                 28 
               
               
                 CFHL 
                   
                   
                   
                   
               
               
                 pAAV-HSP70- 
                 CFHL 
                 HSP70 
                 16 
                 29 
               
               
                 CFHL 
                   
                   
                   
                   
               
               
                 pAAV-PCK1- 
                 CFHL 
                 PCK1 
                 17 
                 30 
               
               
                 CFHL 
               
               
                   
               
            
           
         
       
     
     Ability of AAV.CFH and AAV.FHL1 Vectors to Transduce Cells and Regulate Complement Activity: 
     The CFH vectors indicated above each will be first tested in vitro in HEK293 and ARPE19 cells via transfection and evaluated for expression of the human CFH and FHL1 protein in both cell pellets and in the supernatant. Techniques like Western blot will be used for protein detection and quantification. Quantitative Real time PCR will be used for determining mRNA expression levels. Regulation of complement activity will be tested in a cell culture model of blue light irradiation of A2E-laden retinal pigment epithelial cells as described in van der Burght et al, Acta Ophthalmol, 2013. Briefly, ARPE-19 cell line is grown to confluence and cultured in standard media plus or minus 10 uM A2E for 4 weeks. RPE are irradiated with blue light. Media is replaced with PBS plus calcium, magnesium and 5.5 mM glucose and cells are irradiated with blue light (430+/−30 nm) for 0, 5 or 10 minutes. RPE cells are incubated with appropriately-complement depleted human serum+/−and transfected with the AAV.CFH and AAV.FHL1 vectors. Immunoreactivity of RPE with cell surface markers, CD46, CD55 and CD59 and C3 and MAC deposition will be assessed by fluorescent microscopy or western blot. Levels of iC3b will be measured by Western Blot. 
     After evaluation in ARPE19 cells, the AAV.CFH and AAV.FHL1 vectors will be tested in mouse models of light-induced retinal degeneration and laser induced choroidal neovascularization via intravitreal injections. Amount of protein produced and its biodistribution in the retina will be tested via Western blot and immunohistochemistry. Rescue of photoreceptor thinning and RPE cell death will be assessed via optical coherence tomography, fundus photography and histological analyses. Immunoreactivity of RPE with cell surface markers, CD46, CD55 and CD59 and C3 and MAC deposition will be assessed by fluorescent microscopy or western blot. Levels of iC3b (cleavage product of C3) will be measured by Western Blot. 
     Appropriate dose for non-human primates will be determined based on mouse studies. Non-human primate studies will be conducted in cynomolgus monkeys via intravitreal injections. Therapeutic benefits will be evaluated based on levels of CFH and FHL1 proteins produced and secreted by the RPE. Amount of secreted CFH and FHL1 protein will be measured in the retina and the choroid compared to uninjected or sham injected cohorts. Increased levels of CFH and FHL1 in the retina and choroid is expected to provide therapeutic benefits in the AMD population with rare mutations that lead to the loss or decreased amount of these protein. 
     Example 2: Transfection of HEK-293T Cells with CFH Plasmids 
     Plasmids capable of expressing CFH or GFP under the control of one of several specific promoters (EF1a.SV40i; EF1a; CRALBP; or AAT1) were transfected into HEK-293T cells. Cells were transfected using 1 mg/L plasmid DNA. Cells were transfected with PEI at a 1:1 DNA:PEI ratio. Cells were cultured for 120 hr and sampled for analysis. Cells were lysed and supernatants were harvested and run on reducing PAGE gel and transferred to membranes for Western blot. Primary antibody for detection of CFH is Quidel goat antiserum to human CFH at 1:1000 at 4° C. with rotation 0/N. Secondary antibody was rabbit anti-goat at 1:5000 for 1 hour at room temperature. Rabbit anti-GAPDH polyclonal antibody is included for loading control (1:1000 dilution) and the secondary antibody was rabbit anti-goat (1:5000) for 1 hour at room temperature.  FIG. 18  depicts the results from the Western blot analysis. Robust CFH expression was observed in cell samples transfected with the CFH plasmid under the control of the EF1a.SV40i; EF1a; or CRALBP promoters, while lower expression was observed in the samples transfected with the CFH plasmid under the control of the AAT1 promoter. No CFH was detected in the negative control samples. The data from the Western Blot was quantified by densitometry and the ratio between the level of CFH expression and the level of GAPDH expression for each sample was calculated ( FIG. 19 ). 
     Example 3: Transfection of HEK Cells with CFH-AAV Vectors 
     HEK-293 cells were transduced for three days with various CFH-AAV2 constructs and supernatant samples were harvested and run on a reducing PAGE gel with various controls such as recombinant CFH, recombinant GFP, untrasfected cell lysate, or cells transfected with recombinant GFP rather than CFH. Quidel goat anti-human CFH (A312) was utilized to detect CFH and the blot was incubated at a 1:1,000 dilution overnight and after washing with rabbit Anti-Goat HRP Secondary (Jackson Immunoresearch) at 1:5000 dilution for 1 hour at room temperature with rotation. The blot was separately incubated with mouse anti-eGFP antibody (Thermo Fisher, Mass. 1-952) at a 1:1,000 dilution overnight and after washing with rabbit anti-goat HRP secondary (Jackson Immunoresearch) at 1:5000 dilution for 1 hour at room temperature with rotation. The results from the Western Blot are depicted in  FIG. 20 . Greater expression of CFH was detected in the supernatant from cells transfected with the AAV-CFH constructs than in non-transfected or mock-transfected cells. 
     Example 4: Intravitreal Treatment of Mice with AAV2-CFH Vectors 
     Mice were intravitreally injected with AAV2-CFH vectors under the control of the EF1a.SV40i or EF1a promoters. Eyes were collected 21 days after injection and immunohistochemistry was performed for detection of CFH protein. Eyes were embedded and section and put on slides by standard methods. Slides were washed for 3×5 minutes in 1×PBS. Sections were blocked with blocking buffer (5% BSA, 10% Donkey serum, 0.5% Triton X-100) at room temperature for 1 hour in dark humidity chamber. Samples were stained with CFH antibody (Novus cat. AF4779-SP) at a concentration of 1:20 overnight at 4° C. in dark humidity chamber. Antibody solution was prepared in blocking buffer. Slides were then washed for 3×5 minutes in 1×PBS. Samples were stained with donkey anti-goat secondary antibody (Thermofisher cat. A11056) at a concentration of 1:1000 at room temperature for 1 hour in a dark humidity chamber. The antibody solution was prepared in blocking buffer. Slides were washed for 3×5 minutes in 1×PBS. Samples were mounted with Hoechst solution and sealed and imaged. CFH was detected using the 555 (Texas Red) channel. Modest CFH protein expression was seen in the ganglion cell layer and weak expression of CFH protein was seen in the inner nuclear layer. 
     Example 5: Treatment of Patients with AMD with AAV Vectors 
     This study will evaluate the efficacy of the vectors of Example 1 for treating patients with AMD. Patients with AMD will be treated with any of the CFH AAV2 vectors, or a control. The vectors will be administered at varying doses between 2.5×10 8  vg to 1.4×10 11  vg/per eye in about 100 μl. The vectors will be administered by intravitreal injection in a solution of PBS with additional NaCl and pluronic. Patients will be monitored for improvements in AMD symptoms. 
     It is expected that the CFH and/or FHL1 AAV2 vector treatments will improve the AMD symptoms. 
     INCORPORATION BY REFERENCE 
     All publications and patents mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent was specifically and individually indicated to be incorporated by reference. 
     While specific embodiments of the subject matter have been discussed, the above specification is illustrative and not restrictive. Many variations will become apparent to those skilled in the art upon review of this specification and the claims below. The full scope of the disclosure should be determined by reference to the claims, along with their full scope of equivalents, and the specification, along with such variations. 
     
       
         
           
               
               
            
               
                 SEQUENCE LISTING 
                   
               
               
                 SEQ ID NO: 1-Codon Optimized Human Factor H Like 1 (FHL1) 
               
               
                 GCGGCCGCCACCATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTATGGGCTA 
               
               
                   
               
               
                 TTTGTGTAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAATACAGAAATTCT 
               
               
                   
               
               
                 GACAGGTTCCTGGTCTGACCAAACATATCCAGAAGGCACCCAGGCTATCTATAA 
               
               
                   
               
               
                 ATGCCGCCCTGGATATAGATCTCTTGGAAATGTAATAATGGTATGCAGGAAGGG 
               
               
                   
               
               
                 AGAATGGGTTGCTCTTAATCCATTAAGGAAATGTCAGAAAAGGCCCTGTGGACA 
               
               
                   
               
               
                 TCCTGGAGATACTCCTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTGAAT 
               
               
                   
               
               
                 ATGGTGTAAAAGCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGAGAT 
               
               
                   
               
               
                 TAATTACCGTGAATGTGACACAGATGGATGGACCAATGATATTCCTATATGTGAA 
               
               
                   
               
               
                 GTTGTGAAGTGTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGT 
               
               
                   
               
               
                 GCAATGGAACCAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGT 
               
               
                   
               
               
                 AACTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATGGT 
               
               
                   
               
               
                 TTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCCCCAGAT 
               
               
                   
               
               
                 GTTATAAATGGATCTCCTATATCTCAGAAGATTATTTATAAGGAGAATGAACGAT 
               
               
                   
               
               
                 TTCAATATAAATGTAACATGGGTTATGAATACAGTGAAAGAGGAGATGCTGTAT 
               
               
                   
               
               
                 GCACTGAATCTGGATGGCGTCCGTTGCCTTCATGTGAAGAAAAATCATGTGATAA 
               
               
                   
               
               
                 TCCTTATATTCCAAATGGTGACTACTCACCTTTAAGGATTAAACACAGAACTGGA 
               
               
                   
               
               
                 GATGAAATCACGTACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGAAATA 
               
               
                   
               
               
                 CAGCAAAATGCACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAAC 
               
               
                   
               
               
                 CTTGTGATTATCCAGACATTAAACATGGAGGTCTATATCATGAGAATATGCGTAG 
               
               
                   
               
               
                 ACCATACTTTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACAT 
               
               
                   
               
               
                 TTTGAGACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGAT 
               
               
                   
               
               
                 GGTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAAATGG 
               
               
                   
               
               
                 ATATAATCAAAATTATGGAAGAAAGTTTGTACAGGGTAAATCTATAGACGTTGCC 
               
               
                   
               
               
                 TGCCATCCTGGCTACGCTCTTCCAAAAGCGCAGACCACAGTTACATGTATGGAGA 
               
               
                   
               
               
                 ATGGCTGGTCTCCTACTCCCAGATGCATCCGTGTCAGCTTTACCCTCTAATAAGCT 
               
               
                   
               
               
                 TGGATCCAGATCT, 
               
               
                   
               
               
                 SEQ ID NO: 2-Codon Optimized Human Factor H Like 1 (FHL1) 
               
               
                 GCGGCCGCCACCATGAGACTGCTGGCTAAAATTATCTGCCTGATGCTGTGGGCTA 
               
               
                   
               
               
                 TCTGCGTCGCTGAGGATTGTAACGAGCTGCCCCCCCGGAGAAATACAGAGATCCT 
               
               
                   
               
               
                 GACCGGCTCTTGGAGCGACCAGACATATCCCGAGGGCACCCAGGCCATCTACAA 
               
               
                   
               
               
                 GTGCAGGCCTGGCTATCGCTCTCTGGGCAACGTGATCATGGTGTGCAGGAAGGG 
               
               
                   
               
               
                 AGAGTGGGTGGCCCTGAATCCCCTGAGGAAGTGCCAGAAGCGCCCTTGTGGACA 
               
               
                   
               
               
                 CCCAGGCGACACACCCTTCGGCACCTTTACACTGACCGGCGGCAACGTGTTCGAG 
               
               
                   
               
               
                 TACGGCGTGAAGGCCGTGTATACCTGCAACGAGGGCTACCAGCTGCTGGGCGAG 
               
               
                   
               
               
                 ATCAATTACAGAGAGTGTGACACAGATGGCTGGACCAACGATATCCCTATCTGC 
               
               
                   
               
               
                 GAGGTGGTGAAGTGTCTGCCTGTGACCGCCCCAGAGAATGGCAAGATCGTGAGC 
               
               
                   
               
               
                 TCCGCCATGGAGCCAGACAGGGAGTATCACTTCGGCCAGGCCGTGCGCTTCGTGT 
               
               
                   
               
               
                 GCAACTCCGGCTACAAGATCGAGGGCGATGAGGAGATGCACTGTAGCGACGATG 
               
               
                   
               
               
                 GCTTCTGGTCCAAGGAGAAGCCCAAGTGCGTGGAGATCAGCTGTAAGTCCCCTG 
               
               
                   
               
               
                 ACGTGATCAATGGCTCTCCAATCAGCCAGAAGATCATCTATAAGGAGAACGAGA 
               
               
                   
               
               
                 GGTTTCAGTACAAGTGCAATATGGGCTACGAGTATTCTGAGAGGGGCGATGCCG 
               
               
                   
               
               
                 TGTGCACAGAGAGCGGATGGCGGCCCCTGCCTTCCTGCGAGGAGAAGTCTTGTG 
               
               
                   
               
               
                 ACAACCCTTATATCCCAAATGGCGATTACAGCCCACTGCGGATCAAGCACAGAA 
               
               
                   
               
               
                 CAGGCGATGAGATCACCTATCAGTGCCGGAACGGCTTTTACCCCGCCACAAGAG 
               
               
                   
               
               
                 GCAATACCGCCAAGTGTACATCCACCGGATGGATCCCAGCACCAAGATGCACCC 
               
               
                   
               
               
                 TGAAGCCCTGTGACTATCCTGATATCAAGCACGGCGGCCTGTATCACGAGAACAT 
               
               
                   
               
               
                 GAGACGGCCCTACTTCCCTGTGGCCGTGGGCAAGTACTATTCCTACTATTGCGAC 
               
               
                   
               
               
                 GAGCACTTTGAGACACCCTCCGGCTCTTACTGGGACCACATCCACTGTACCCAGG 
               
               
                   
               
               
                 ATGGATGGAGCCCCGCAGTGCCATGCCTGAGGAAGTGTTACTTCCCTTATCTGGA 
               
               
                   
               
               
                 GAATGGCTACAACCAGAATTATGGCCGCAAGTTTGTGCAGGGCAAGAGCATCGA 
               
               
                   
               
               
                 TGTGGCATGCCACCCAGGATACGCACTGCCAAAGGCACAGACCACAGTGACCTG 
               
               
                   
               
               
                 TATGGAAAACGGCTGGTCCCCTACCCCTCGCTGTATCAGAGTGTCATTCACCCTG 
               
               
                   
               
               
                 TAATAAGCTTGGATCCAGATCT 
               
               
                   
               
               
                 SEQ ID NO: 3-Non-Codon Optimized Human Factor H Like 1 (FHL1) 
               
               
                 GCGGCCGCCACCATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTATGGGCTA 
               
               
                   
               
               
                 TTTGTGTAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAATACAGAAATTCT 
               
               
                   
               
               
                 GACAGGTTCCTGGTCTGACCAAACATATCCAGAAGGCACCCAGGCTATCTATAA 
               
               
                   
               
               
                 ATGCCGCCCTGGATATCGAAGTCTTGGAAATGTAATAATGGTATGCAGGAAGGG 
               
               
                   
               
               
                 AGAATGGGTTGCTCTTAATCCATTAAGGAAATGTCAGAAAAGGCCCTGTGGACA 
               
               
                   
               
               
                 TCCTGGAGATACTCCTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTGAAT 
               
               
                   
               
               
                 ATGGTGTAAAAGCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGAGAT 
               
               
                   
               
               
                 TAATTACCGTGAATGTGACACAGATGGATGGACCAATGATATTCCTATATGTGAA 
               
               
                   
               
               
                 GTTGTGAAGTGTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGT 
               
               
                   
               
               
                 GCAATGGAACCAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGT 
               
               
                   
               
               
                 AACTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATGGT 
               
               
                   
               
               
                 TTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCCCCAGAT 
               
               
                   
               
               
                 GTTATAAATGGATCTCCTATATCTCAGAAGATTATTTATAAGGAGAATGAACGAT 
               
               
                   
               
               
                 TTCAATATAAATGTAACATGGGTTATGAATACAGTGAAAGAGGAGATGCTGTAT 
               
               
                   
               
               
                 GCACTGAATCTGGATGGCGTCCGTTGCCTTCATGTGAAGAAAAATCATGTGATAA 
               
               
                   
               
               
                 TCCTTATATTCCAAATGGTGACTACTCACCTTTAAGGATTAAACACAGAACTGGA 
               
               
                   
               
               
                 GATGAAATCACGTACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGAAATA 
               
               
                   
               
               
                 CAGCAAAATGCACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAAC 
               
               
                   
               
               
                 CTTGTGATTATCCAGACATTAAACATGGAGGTCTATATCATGAGAATATGCGTAG 
               
               
                   
               
               
                 ACCATACTTTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACAT 
               
               
                   
               
               
                 TTTGAGACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGAT 
               
               
                   
               
               
                 GGTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAAATGG 
               
               
                   
               
               
                 ATATAATCAAAATTATGGAAGAAAGTTTGTACAGGGTAAATCTATAGACGTTGCC 
               
               
                   
               
               
                 TGCCATCCTGGCTACGCTCTTCCAAAAGCGCAGACCACAGTTACATGTATGGAGA 
               
               
                   
               
               
                 ATGGCTGGTCTCCTACTCCCAGATGCATCCGTGTCAGCTTTACCCTCTAATAAGCT 
               
               
                   
               
               
                 TGGATCCAGATCT 
               
               
                   
               
               
                 SEQ ID NO: 4: SFTL Sequence 
               
               
                 SFTL 
               
               
                   
               
               
                 SEQ ID NO: 5-CFH Nucleotide Sequence 
               
               
                 ATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTATGGGCTATTTGTGTAGCAG 
               
               
                   
               
               
                 AAGATTGCAATGAACTTCCTCCAAGAAGAAATACAGAAATTCTGACAGGTTCCT 
               
               
                   
               
               
                 GGTCTGACCAAACATATCCAGAAGGCACCCAGGCTATCTATAAATGCCGCCCTG 
               
               
                   
               
               
                 GATATAGATCTCTTGGAAATGTAATAATGGTATGCAGGAAGGGAGAATGGGTTG 
               
               
                   
               
               
                 CTCTTAATCCATTAAGGAAATGTCAGAAAAGGCCCTGTGGACATCCTGGAGATAC 
               
               
                   
               
               
                 TCCTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGTAAAA 
               
               
                   
               
               
                 GCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTACCGTG 
               
               
                   
               
               
                 AATGTGACACAGATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGAAGTG 
               
               
                   
               
               
                 TTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATGGAACC 
               
               
                   
               
               
                 AGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGTAACTCAGGCTAC 
               
               
                   
               
               
                 AAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATGGTTTTTGGAGTAAA 
               
               
                   
               
               
                 GAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCCCCAGATGTTATAAATGGA 
               
               
                   
               
               
                 TCTCCTATATCTCAGAAGATTATTTATAAGGAGAATGAACGATTTCAATATAAAT 
               
               
                   
               
               
                 GTAACATGGGTTATGAATACAGTGAAAGAGGAGATGCTGTATGCACTGAATCTG 
               
               
                   
               
               
                 GATGGCGTCCGTTGCCTTCATGTGAAGAAAAATCATGTGATAATCCTTATATTCC 
               
               
                   
               
               
                 AAATGGTGACTACTCACCTTTAAGGATTAAACACAGAACTGGAGATGAAATCAC 
               
               
                   
               
               
                 GTACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAAATG 
               
               
                   
               
               
                 CACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGATTAT 
               
               
                   
               
               
                 CCAGACATTAAACATGGAGGTCTATATCATGAGAATATGCGTAGACCATACTTTC 
               
               
                   
               
               
                 CAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACATTTTGAGACTCC 
               
               
                   
               
               
                 GTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGATGGTCGCCAGC 
               
               
                   
               
               
                 AGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAAATGGATATAATCAA 
               
               
                   
               
               
                 AATTATGGAAGAAAGTTTGTACAGGGTAAATCTATAGACGTTGCCTGCCATCCTG 
               
               
                   
               
               
                 GCTACGCTCTTCCAAAAGCGCAGACCACAGTTACATGTATGGAGAATGGCTGGTC 
               
               
                   
               
               
                 TCCTACTCCCAGATGCATCCGTGTCAAAACATGTTCCAAATCAAGTATAGATATT 
               
               
                   
               
               
                 GAGAATGGGTTTATTTCTGAATCTCAGTATACATATGCCTTAAAAGAAAAAGCGA 
               
               
                   
               
               
                 AATATCAATGCAAACTAGGATATGTAACAGCAGATGGTGAAACATCAGGATCAA 
               
               
                   
               
               
                 TTACATGTGGGAAAGATGGATGGTCAGCTCAACCCACGTGCATTAAATCTTGTGA 
               
               
                   
               
               
                 TATCCCAGTATTTATGAATGCCAGAACTAAAAATGACTTCACATGGTTTAAGCTG 
               
               
                   
               
               
                 AATGACACATTGGACTATGAATGCCATGATGGTTATGAAAGCAATACTGGAAGC 
               
               
                   
               
               
                 ACCACTGGTTCCATAGTGTGTGGTTACAATGGTTGGTCTGATTTACCCATATGTTA 
               
               
                   
               
               
                 TGAAAGAGAATGCGAACTTCCTAAAATAGATGTACACTTAGTTCCTGATCGCAAG 
               
               
                   
               
               
                 AAAGACCAGTATAAAGTTGGAGAGGTGTTGAAATTCTCCTGCAAACCAGGATTT 
               
               
                   
               
               
                 ACAATAGTTGGACCTAATTCCGTTCAGTGCTACCACTTTGGATTGTCTCCTGACCT 
               
               
                   
               
               
                 CCCAATATGTAAAGAGCAAGTACAATCATGTGGTCCACCTCCTGAACTCCTCAAT 
               
               
                   
               
               
                 GGGAATGTTAAGGAAAAAACGAAAGAAGAATATGGACACAGTGAAGTGGTGGA 
               
               
                   
               
               
                 ATATTATTGCAATCCTAGATTTCTAATGAAGGGACCTAATAAAATTCAATGTGTT 
               
               
                   
               
               
                 GATGGAGAGTGGACAACTTTACCAGTGTGTATTGTGGAGGAGAGTACCTGTGGA 
               
               
                   
               
               
                 GATATACCTGAACTTGAACATGGCTGGGCCCAGCTTTCTTCCCCTCCTTATTACTA 
               
               
                   
               
               
                 TGGAGATTCAGTGGAATTCAATTGCTCAGAATCATTTACAATGATTGGACACAGA 
               
               
                   
               
               
                 TCAATTACGTGTATTCATGGAGTATGGACCCAACTTCCCCAGTGTGTGGCAATAG 
               
               
                   
               
               
                 ATAAACTTAAGAAGTGCAAATCATCAAATTTAATTATACTTGAGGAACATTTAAA 
               
               
                   
               
               
                 AAACAAGAAGGAATTCGATCATAATTCTAACATAAGGTACAGATGTAGAGGAAA 
               
               
                   
               
               
                 AGAAGGATGGATACACACAGTCTGCATAAATGGAAGATGGGATCCAGAAGTGAA 
               
               
                   
               
               
                 CTGCTCAATGGCACAAATACAATTATGCCCACCTCCACCTCAGATTCCCAATTCT 
               
               
                   
               
               
                 CACAATATGACAACCACACTGAATTATCGGGATGGAGAAAAAGTATCTGTTCTTT 
               
               
                   
               
               
                 GCCAAGAAAATTATCTAATTCAGGAAGGAGAAGAAATTACATGCAAAGATGGAA 
               
               
                   
               
               
                 GATGGCAGTCAATACCACTCTGTGTTGAAAAAATTCCATGTTCACAACCACCTCA 
               
               
                   
               
               
                 GATAGAACACGGAACCATTAATTCATCCAGGTCTTCACAAGAAAGTTATGCACAT 
               
               
                   
               
               
                 GGGACTAAATTGAGTTATACTTGTGAGGGTGGTTTCAGGATATCTGAAGAAAATG 
               
               
                   
               
               
                 AAACAACATGCTACATGGGAAAATGGAGTTCTCCACCTCAGTGTGAAGGCCTTCC 
               
               
                   
               
               
                 TTGTAAATCTCCACCTGAGATTTCTCATGGTGTTGTAGCTCACATGTCAGACAGTT 
               
               
                   
               
               
                 ATCAGTATGGAGAAGAAGTTACGTACAAATGTTTTGAAGGTTTTGGAATTGATGG 
               
               
                   
               
               
                 GCCTGCAATTGCAAAATGCTTAGGAGAAAAATGGTCTCACCCTCCATCATGCATA 
               
               
                   
               
               
                 AAAACAGATTGTCTCAGTTTACCTAGCTTTGAAAATGCCATACCCATGGGAGAGA 
               
               
                   
               
               
                 AGAAGGATGTGTATAAGGCGGGTGAGCAAGTGACTTACACTTGTGCAACATATT 
               
               
                   
               
               
                 ACAAAATGGATGGAGCCAGTAATGTAACATGCATTAATAGCAGATGGACAGGAA 
               
               
                   
               
               
                 GGCCAACATGCAGAGACACCTCCTGTGTGAATCCGCCCACAGTACAAAATGCTT 
               
               
                   
               
               
                 ATATAGTGTCGAGACAGATGAGTAAATATCCATCTGGTGAGAGAGTACGTTATC 
               
               
                   
               
               
                 AATGTAGGAGCCCTTATGAAATGTTTGGGGATGAAGAAGTGATGTGTTTAAATG 
               
               
                   
               
               
                 GAAACTGGACGGAACCACCTCAATGCAAAGATTCTACAGGAAAATGTGGGCCCC 
               
               
                   
               
               
                 CTCCACCTATTGACAATGGGGACATTACTTCATTCCCGTTGTCAGTATATGCTCCA 
               
               
                   
               
               
                 GCTTCATCAGTTGAGTACCAATGCCAGAACTTGTATCAACTTGAGGGTAACAAGC 
               
               
                   
               
               
                 GAATAACATGTAGAAATGGACAATGGTCAGAACCACCAAAATGCTTACATCCGT 
               
               
                   
               
               
                 GTGTAATATCCCGAGAAATTATGGAAAATTATAACATAGCATTAAGGTGGACAG 
               
               
                   
               
               
                 CCAAACAGAAGCTTTATTCGAGAACAGGTGAATCAGTTGAATTTGTGTGTAAACG 
               
               
                   
               
               
                 GGGATATCGTCTTTCATCACGTTCTCACACATTGCGAACAACATGTTGGGATGGG 
               
               
                   
               
               
                 AAACTGGAGTATCCAACTTGTGCAAAAAGATAG 
               
               
                   
               
               
                 SEQ ID NO: 6-CRALBP Promoter 
               
               
                 ACGCGTTAACTAGTACCCTGGTGGTGGTGGTGGGGGGGGGGGGGTGCTCTCTCA 
               
               
                   
               
               
                 GCAACCCCACCCCGGGATCTTGAGGAGAAAGAGGGCAGAGAAAAGAGGGAATG 
               
               
                   
               
               
                 GGACTGGCCCAGATCCCAGCCCCACAGCCGGGCTTCCACATGGCCGAGCAGGAA 
               
               
                   
               
               
                 CTCCAGAGCAGGAGCACACAAAGGAGGGCTTTGATGCGCCTCCAGCCAGGCCCA 
               
               
                   
               
               
                 GGCCTCTCCCCTCTCCCCTTTCTCTCTGGGTCTTCCTTTGCCCCACTGAGGGCCTC 
               
               
                   
               
               
                 CTGTGAGCCCGATTTAACGGAAACTGTGGGCGGTGAGAAGTTCCTTATGACACAC 
               
               
                   
               
               
                 TAATCCCAACCTGCTGACCGGACCACGCCTCCAGCGGAGGGAACCTCTAGAGCT 
               
               
                   
               
               
                 CCAGGACATTCAGGTACCAGGTAGCCCCAAGGAGGAGCTGCCGACCATCGAT 
               
               
                   
               
               
                 SEQ ID NO: 7-Rrepresentative CFH AAV vector (with CRALBP  
               
               
                 Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCG 
               
               
                   
               
               
                 GGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAG 
               
               
                   
               
               
                 AGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTTAACTAGT 
               
               
                   
               
               
                 ACCCTGGTGGTGGTGGTGGGGGGGGGGGGGTGCTCTCTCAGCAACCCCACCCCG 
               
               
                   
               
               
                 GGATCTTGAGGAGAAAGAGGGCAGAGAAAAGAGGGAATGGGACTGGCCCAGAT 
               
               
                   
               
               
                 CCCAGCCCCACAGCCGGGCTTCCACATGGCCGAGCAGGAACTCCAGAGCAGGAG 
               
               
                   
               
               
                 CACACAAAGGAGGGCTTTGATGCGCCTCCAGCCAGGCCCAGGCCTCTCCCCTCTC 
               
               
                   
               
               
                 CCCTTTCTCTCTGGGTCTTCCTTTGCCCCACTGAGGGCCTCCTGTGAGCCCGATTT 
               
               
                   
               
               
                 AACGGAAACTGTGGGCGGTGAGAAGTTCCTTATGACACACTAATCCCAACCTGCT 
               
               
                   
               
               
                 GACCGGACCACGCCTCCAGCGGAGGGAACCTCTAGAGCTCCAGGACATTCAGGT 
               
               
                   
               
               
                 ACCAGGTAGCCCCAAGGAGGAGCTGCCGACCATCGATAGCTGCAGGCGGCCGCC 
               
               
                   
               
               
                 GCCACCATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTATGGGCTATTTGTGT 
               
               
                   
               
               
                 AGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAATACAGAAATTCTGACAGG 
               
               
                   
               
               
                 TTCCTGGTCTGACCAAACATATCCAGAAGGCACCCAGGCTATCTATAAATGCCGC 
               
               
                   
               
               
                 CCTGGATATAGATCTCTTGGAAATGTAATAATGGTATGCAGGAAGGGAGAATGG 
               
               
                   
               
               
                 GTTGCTCTTAATCCATTAAGGAAATGTCAGAAAAGGCCCTGTGGACATCCTGGAG 
               
               
                   
               
               
                 ATACTCCTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGTA 
               
               
                   
               
               
                 AAAGCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTACC 
               
               
                   
               
               
                 GTGAATGTGACACAGATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGAA 
               
               
                   
               
               
                 GTGTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATGGA 
               
               
                   
               
               
                 ACCAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGTAACTCAGGC 
               
               
                   
               
               
                 TACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATGGTTTTTGGAGT 
               
               
                   
               
               
                 AAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCCCCAGATGTTATAAAT 
               
               
                   
               
               
                 GGATCTCCTATATCTCAGAAGATTATTTATAAGGAGAATGAACGATTTCAATATA 
               
               
                   
               
               
                 AATGTAACATGGGTTATGAATACAGTGAAAGAGGAGATGCTGTATGCACTGAAT 
               
               
                   
               
               
                 CTGGATGGCGTCCGTTGCCTTCATGTGAAGAAAAATCATGTGATAATCCTTATAT 
               
               
                   
               
               
                 TCCAAATGGTGACTACTCACCTTTAAGGATTAAACACAGAACTGGAGATGAAAT 
               
               
                   
               
               
                 CACGTACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAA 
               
               
                   
               
               
                 ATGCACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGAT 
               
               
                   
               
               
                 TATCCAGACATTAAACATGGAGGTCTATATCATGAGAATATGCGTAGACCATACT 
               
               
                   
               
               
                 TTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACATTTTGAGAC 
               
               
                   
               
               
                 TCCGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGATGGTCGCCA 
               
               
                   
               
               
                 GCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAAATGGATATAATC 
               
               
                   
               
               
                 AAAATTATGGAAGAAAGTTTGTACAGGGTAAATCTATAGACGTTGCCTGCCATCC 
               
               
                   
               
               
                 TGGCTACGCTCTTCCAAAAGCGCAGACCACAGTTACATGTATGGAGAATGGCTG 
               
               
                   
               
               
                 GTCTCCTACTCCCAGATGCATCCGTGTCAAAACATGTTCCAAATCAAGTATAGAT 
               
               
                   
               
               
                 ATTGAGAATGGGTTTATTTCTGAATCTCAGTATACATATGCCTTAAAAGAAAAAG 
               
               
                   
               
               
                 CGAAATATCAATGCAAACTAGGATATGTAACAGCAGATGGTGAAACATCAGGAT 
               
               
                   
               
               
                 CAATTACATGTGGGAAAGATGGATGGTCAGCTCAACCCACGTGCATTAAATCTTG 
               
               
                   
               
               
                 TGATATCCCAGTATTTATGAATGCCAGAACTAAAAATGACTTCACATGGTTTAAG 
               
               
                   
               
               
                 CTGAATGACACATTGGACTATGAATGCCATGATGGTTATGAAAGCAATACTGGA 
               
               
                   
               
               
                 AGCACCACTGGTTCCATAGTGTGTGGTTACAATGGTTGGTCTGATTTACCCATAT 
               
               
                   
               
               
                 GTTATGAAAGAGAATGCGAACTTCCTAAAATAGATGTACACTTAGTTCCTGATCG 
               
               
                   
               
               
                 CAAGAAAGACCAGTATAAAGTTGGAGAGGTGTTGAAATTCTCCTGCAAACCAGG 
               
               
                   
               
               
                 ATTTACAATAGTTGGACCTAATTCCGTTCAGTGCTACCACTTTGGATTGTCTCCTG 
               
               
                   
               
               
                 ACCTCCCAATATGTAAAGAGCAAGTACAATCATGTGGTCCACCTCCTGAACTCCT 
               
               
                   
               
               
                 CAATGGGAATGTTAAGGAAAAAACGAAAGAAGAATATGGACACAGTGAAGTGG 
               
               
                   
               
               
                 TGGAATATTATTGCAATCCTAGATTTCTAATGAAGGGACCTAATAAAATTCAATG 
               
               
                   
               
               
                 TGTTGATGGAGAGTGGACAACTTTACCAGTGTGTATTGTGGAGGAGAGTACCTGT 
               
               
                   
               
               
                 GGAGATATACCTGAACTTGAACATGGCTGGGCCCAGCTTTCTTCCCCTCCTTATT 
               
               
                   
               
               
                 ACTATGGAGATTCAGTGGAATTCAATTGCTCAGAATCATTTACAATGATTGGACA 
               
               
                   
               
               
                 CAGATCAATTACGTGTATTCATGGAGTATGGACCCAACTTCCCCAGTGTGTGGCA 
               
               
                   
               
               
                 ATAGATAAACTTAAGAAGTGCAAATCATCAAATTTAATTATACTTGAGGAACATT 
               
               
                   
               
               
                 TAAAAAACAAGAAGGAATTCGATCATAATTCTAACATAAGGTACAGATGTAGAG 
               
               
                   
               
               
                 GAAAAGAAGGATGGATACACACAGTCTGCATAAATGGAAGATGGGATCCAGAA 
               
               
                   
               
               
                 GTGAACTGCTCAATGGCACAAATACAATTATGCCCACCTCCACCTCAGATTCCCA 
               
               
                   
               
               
                 ATTCTCACAATATGACAACCACACTGAATTATCGGGATGGAGAAAAAGTATCTGT 
               
               
                   
               
               
                 TCTTTGCCAAGAAAATTATCTAATTCAGGAAGGAGAAGAAATTACATGCAAAGA 
               
               
                   
               
               
                 TGGAAGATGGCAGTCAATACCACTCTGTGTTGAAAAAATTCCATGTTCACAACCA 
               
               
                   
               
               
                 CCTCAGATAGAACACGGAACCATTAATTCATCCAGGTCTTCACAAGAAAGTTATG 
               
               
                   
               
               
                 CACATGGGACTAAATTGAGTTATACTTGTGAGGGTGGTTTCAGGATATCTGAAGA 
               
               
                   
               
               
                 AAATGAAACAACATGCTACATGGGAAAATGGAGTTCTCCACCTCAGTGTGAAGG 
               
               
                   
               
               
                 CCTTCCTTGTAAATCTCCACCTGAGATTTCTCATGGTGTTGTAGCTCACATGTCAG 
               
               
                   
               
               
                 ACAGTTATCAGTATGGAGAAGAAGTTACGTACAAATGTTTTGAAGGTTTTGGAAT 
               
               
                   
               
               
                 TGATGGGCCTGCAATTGCAAAATGCTTAGGAGAAAAATGGTCTCACCCTCCATCA 
               
               
                   
               
               
                 TGCATAAAAACAGATTGTCTCAGTTTACCTAGCTTTGAAAATGCCATACCCATGG 
               
               
                   
               
               
                 GAGAGAAGAAGGATGTGTATAAGGCGGGTGAGCAAGTGACTTACACTTGTGCAA 
               
               
                   
               
               
                 CATATTACAAAATGGATGGAGCCAGTAATGTAACATGCATTAATAGCAGATGGA 
               
               
                   
               
               
                 CAGGAAGGCCAACATGCAGAGACACCTCCTGTGTGAATCCGCCCACAGTACAAA 
               
               
                   
               
               
                 ATGCTTATATAGTGTCGAGACAGATGAGTAAATATCCATCTGGTGAGAGAGTAC 
               
               
                   
               
               
                 GTTATCAATGTAGGAGCCCTTATGAAATGTTTGGGGATGAAGAAGTGATGTGTTT 
               
               
                   
               
               
                 AAATGGAAACTGGACGGAACCACCTCAATGCAAAGATTCTACAGGAAAATGTGG 
               
               
                   
               
               
                 GCCCCCTCCACCTATTGACAATGGGGACATTACTTCATTCCCGTTGTCAGTATATG 
               
               
                   
               
               
                 CTCCAGCTTCATCAGTTGAGTACCAATGCCAGAACTTGTATCAACTTGAGGGTAA 
               
               
                   
               
               
                 CAAGCGAATAACATGTAGAAATGGACAATGGTCAGAACCACCAAAATGCTTACA 
               
               
                   
               
               
                 TCCGTGTGTAATATCCCGAGAAATTATGGAAAATTATAACATAGCATTAAGGTGG 
               
               
                   
               
               
                 ACAGCCAAACAGAAGCTTTATTCGAGAACAGGTGAATCAGTTGAATTTGTGTGTA 
               
               
                   
               
               
                 AACGGGGATATCGTCTTTCATCACGTTCTCACACATTGCGAACAACATGTTGGGA 
               
               
                   
               
               
                 TGGGAAACTGGAGTATCCAACTTGTGCAAAAAGATAGCTGTGCCTTCTAGTTGCC 
               
               
                   
               
               
                 AGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACT 
               
               
                   
               
               
                 CCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGT 
               
               
                   
               
               
                 GTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGG 
               
               
                   
               
               
                 AAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGGTTAACTCGAGG 
               
               
                   
               
               
                 GATCCCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCT 
               
               
                   
               
               
                 CTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCC 
               
               
                   
               
               
                 GGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGG 
               
               
                   
               
               
                 GCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATAC 
               
               
                   
               
               
                 GTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT 
               
               
                   
               
               
                 GGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCT 
               
               
                   
               
               
                 TTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTA 
               
               
                   
               
               
                 AATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCA 
               
               
                   
               
               
                 AAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGT 
               
               
                   
               
               
                 TTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAA 
               
               
                   
               
               
                 CTGGAACAACACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTG 
               
               
                   
               
               
                 CCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGA 
               
               
                   
               
               
                 ATTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGC 
               
               
                   
               
               
                 TCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGC 
               
               
                   
               
               
                 CCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTC 
               
               
                   
               
               
                 CGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGAGACG 
               
               
                   
               
               
                 AAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTT 
               
               
                   
               
               
                 TCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTT 
               
               
                   
               
               
                 TATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATA 
               
               
                   
               
               
                 AATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTC 
               
               
                   
               
               
                 GCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACG 
               
               
                   
               
               
                 CTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATC 
               
               
                   
               
               
                 GAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTT 
               
               
                   
               
               
                 TTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATT 
               
               
                   
               
               
                 GACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTG 
               
               
                   
               
               
                 GTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGA 
               
               
                   
               
               
                 GAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTC 
               
               
                   
               
               
                 TGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGG 
               
               
                   
               
               
                 ATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAA 
               
               
                   
               
               
                 ACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAAC 
               
               
                   
               
               
                 TATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGAT 
               
               
                   
               
               
                 GGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGG 
               
               
                   
               
               
                 TTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAG 
               
               
                   
               
               
                 CACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGA 
               
               
                   
               
               
                 GTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCAC 
               
               
                   
               
               
                 TGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGA 
               
               
                   
               
               
                 TTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATC 
               
               
                   
               
               
                 TCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGT 
               
               
                   
               
               
                 AGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCT 
               
               
                   
               
               
                 TGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGC 
               
               
                   
               
               
                 TACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATAC 
               
               
                   
               
               
                 TGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCG 
               
               
                   
               
               
                 CCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATA 
               
               
                   
               
               
                 AGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGC 
               
               
                   
               
               
                 GGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCT 
               
               
                   
               
               
                 ACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCG 
               
               
                   
               
               
                 AAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAG 
               
               
                   
               
               
                 CGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGT 
               
               
                   
               
               
                 TTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAG 
               
               
                   
               
               
                 CCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGG 
               
               
                   
               
               
                 CCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 8-EF1a Promoter 
               
               
                 ACGCGTTAACTAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGG 
               
               
                   
               
               
                 GGGAGGGGTCGGCAATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTG 
               
               
                   
               
               
                 GGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGAACCG 
               
               
                   
               
               
                 TATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCA 
               
               
                   
               
               
                 GAACACAG 
               
               
                   
               
               
                 SEQ ID NO: 9-Representative CFH AAV vector (EF1a promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCG 
               
               
                   
               
               
                 GGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAG 
               
               
                   
               
               
                 AGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTTAACTAGT 
               
               
                   
               
               
                 GGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCA 
               
               
                   
               
               
                 ATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCG 
               
               
                   
               
               
                 TGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGT 
               
               
                   
               
               
                 AGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACAGATCGAT 
               
               
                   
               
               
                 AGCTGCAGGCGGCCGCCGCCACCATGAGACTTCTAGCAAAGATTATTTGCCTTAT 
               
               
                   
               
               
                 GTTATGGGCTATTTGTGTAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAAT 
               
               
                   
               
               
                 ACAGAAATTCTGACAGGTTCCTGGTCTGACCAAACATATCCAGAAGGCACCCAG 
               
               
                   
               
               
                 GCTATCTATAAATGCCGCCCTGGATATAGATCTCTTGGAAATGTAATAATGGTAT 
               
               
                   
               
               
                 GCAGGAAGGGAGAATGGGTTGCTCTTAATCCATTAAGGAAATGTCAGAAAAGGC 
               
               
                   
               
               
                 CCTGTGGACATCCTGGAGATACTCCTTTTGGTACTTTTACCCTTACAGGAGGAAA 
               
               
                   
               
               
                 TGTGTTTGAATATGGTGTAAAAGCTGTGTATACATGTAATGAGGGGTATCAATTG 
               
               
                   
               
               
                 CTAGGTGAGATTAATTACCGTGAATGTGACACAGATGGATGGACCAATGATATTC 
               
               
                   
               
               
                 CTATATGTGAAGTTGTGAAGTGTTTACCAGTGACAGCACCAGAGAATGGAAAAA 
               
               
                   
               
               
                 TTGTCAGTAGTGCAATGGAACCAGATCGGGAATACCATTTTGGACAAGCAGTAC 
               
               
                   
               
               
                 GGTTTGTATGTAACTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATTGTTC 
               
               
                   
               
               
                 AGACGATGGTTTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAA 
               
               
                   
               
               
                 ATCCCCAGATGTTATAAATGGATCTCCTATATCTCAGAAGATTATTTATAAGGAG 
               
               
                   
               
               
                 AATGAACGATTTCAATATAAATGTAACATGGGTTATGAATACAGTGAAAGAGGA 
               
               
                   
               
               
                 GATGCTGTATGCACTGAATCTGGATGGCGTCCGTTGCCTTCATGTGAAGAAAAAT 
               
               
                   
               
               
                 CATGTGATAATCCTTATATTCCAAATGGTGACTACTCACCTTTAAGGATTAAACA 
               
               
                   
               
               
                 CAGAACTGGAGATGAAATCACGTACCAGTGTAGAAATGGTTTTTATCCTGCAACC 
               
               
                   
               
               
                 CGGGGAAATACAGCAAAATGCACAAGTACTGGCTGGATACCTGCTCCGAGATGT 
               
               
                   
               
               
                 ACCTTGAAACCTTGTGATTATCCAGACATTAAACATGGAGGTCTATATCATGAGA 
               
               
                   
               
               
                 ATATGCGTAGACCATACTTTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTG 
               
               
                   
               
               
                 TGATGAACATTTTGAGACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCACA 
               
               
                   
               
               
                 CAAGATGGATGGTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATT 
               
               
                   
               
               
                 TGGAAAATGGATATAATCAAAATTATGGAAGAAAGTTTGTACAGGGTAAATCTA 
               
               
                   
               
               
                 TAGACGTTGCCTGCCATCCTGGCTACGCTCTTCCAAAAGCGCAGACCACAGTTAC 
               
               
                   
               
               
                 ATGTATGGAGAATGGCTGGTCTCCTACTCCCAGATGCATCCGTGTCAAAACATGT 
               
               
                   
               
               
                 TCCAAATCAAGTATAGATATTGAGAATGGGTTTATTTCTGAATCTCAGTATACAT 
               
               
                   
               
               
                 ATGCCTTAAAAGAAAAAGCGAAATATCAATGCAAACTAGGATATGTAACAGCAG 
               
               
                   
               
               
                 ATGGTGAAACATCAGGATCAATTACATGTGGGAAAGATGGATGGTCAGCTCAAC 
               
               
                   
               
               
                 CCACGTGCATTAAATCTTGTGATATCCCAGTATTTATGAATGCCAGAACTAAAAA 
               
               
                   
               
               
                 TGACTTCACATGGTTTAAGCTGAATGACACATTGGACTATGAATGCCATGATGGT 
               
               
                   
               
               
                 TATGAAAGCAATACTGGAAGCACCACTGGTTCCATAGTGTGTGGTTACAATGGTT 
               
               
                   
               
               
                 GGTCTGATTTACCCATATGTTATGAAAGAGAATGCGAACTTCCTAAAATAGATGT 
               
               
                   
               
               
                 ACACTTAGTTCCTGATCGCAAGAAAGACCAGTATAAAGTTGGAGAGGTGTTGAA 
               
               
                   
               
               
                 ATTCTCCTGCAAACCAGGATTTACAATAGTTGGACCTAATTCCGTTCAGTGCTAC 
               
               
                   
               
               
                 CACTTTGGATTGTCTCCTGACCTCCCAATATGTAAAGAGCAAGTACAATCATGTG 
               
               
                   
               
               
                 GTCCACCTCCTGAACTCCTCAATGGGAATGTTAAGGAAAAAACGAAAGAAGAAT 
               
               
                   
               
               
                 ATGGACACAGTGAAGTGGTGGAATATTATTGCAATCCTAGATTTCTAATGAAGGG 
               
               
                   
               
               
                 ACCTAATAAAATTCAATGTGTTGATGGAGAGTGGACAACTTTACCAGTGTGTATT 
               
               
                   
               
               
                 GTGGAGGAGAGTACCTGTGGAGATATACCTGAACTTGAACATGGCTGGGCCCAG 
               
               
                   
               
               
                 CTTTCTTCCCCTCCTTATTACTATGGAGATTCAGTGGAATTCAATTGCTCAGAATC 
               
               
                   
               
               
                 ATTTACAATGATTGGACACAGATCAATTACGTGTATTCATGGAGTATGGACCCAA 
               
               
                   
               
               
                 CTTCCCCAGTGTGTGGCAATAGATAAACTTAAGAAGTGCAAATCATCAAATTTAA 
               
               
                   
               
               
                 TTATACTTGAGGAACATTTAAAAAACAAGAAGGAATTCGATCATAATTCTAACAT 
               
               
                   
               
               
                 AAGGTACAGATGTAGAGGAAAAGAAGGATGGATACACACAGTCTGCATAAATG 
               
               
                   
               
               
                 GAAGATGGGATCCAGAAGTGAACTGCTCAATGGCACAAATACAATTATGCCCAC 
               
               
                   
               
               
                 CTCCACCTCAGATTCCCAATTCTCACAATATGACAACCACACTGAATTATCGGGA 
               
               
                   
               
               
                 TGGAGAAAAAGTATCTGTTCTTTGCCAAGAAAATTATCTAATTCAGGAAGGAGA 
               
               
                   
               
               
                 AGAAATTACATGCAAAGATGGAAGATGGCAGTCAATACCACTCTGTGTTGAAAA 
               
               
                   
               
               
                 AATTCCATGTTCACAACCACCTCAGATAGAACACGGAACCATTAATTCATCCAGG 
               
               
                   
               
               
                 TCTTCACAAGAAAGTTATGCACATGGGACTAAATTGAGTTATACTTGTGAGGGTG 
               
               
                   
               
               
                 GTTTCAGGATATCTGAAGAAAATGAAACAACATGCTACATGGGAAAATGGAGTT 
               
               
                   
               
               
                 CTCCACCTCAGTGTGAAGGCCTTCCTTGTAAATCTCCACCTGAGATTTCTCATGGT 
               
               
                   
               
               
                 GTTGTAGCTCACATGTCAGACAGTTATCAGTATGGAGAAGAAGTTACGTACAAAT 
               
               
                   
               
               
                 GTTTTGAAGGTTTTGGAATTGATGGGCCTGCAATTGCAAAATGCTTAGGAGAAAA 
               
               
                   
               
               
                 ATGGTCTCACCCTCCATCATGCATAAAAACAGATTGTCTCAGTTTACCTAGCTTTG 
               
               
                   
               
               
                 AAAATGCCATACCCATGGGAGAGAAGAAGGATGTGTATAAGGCGGGTGAGCAA 
               
               
                   
               
               
                 GTGACTTACACTTGTGCAACATATTACAAAATGGATGGAGCCAGTAATGTAACAT 
               
               
                   
               
               
                 GCATTAATAGCAGATGGACAGGAAGGCCAACATGCAGAGACACCTCCTGTGTGA 
               
               
                   
               
               
                 ATCCGCCCACAGTACAAAATGCTTATATAGTGTCGAGACAGATGAGTAAATATCC 
               
               
                   
               
               
                 ATCTGGTGAGAGAGTACGTTATCAATGTAGGAGCCCTTATGAAATGTTTGGGGAT 
               
               
                   
               
               
                 GAAGAAGTGATGTGTTTAAATGGAAACTGGACGGAACCACCTCAATGCAAAGAT 
               
               
                   
               
               
                 TCTACAGGAAAATGTGGGCCCCCTCCACCTATTGACAATGGGGACATTACTTCAT 
               
               
                   
               
               
                 TCCCGTTGTCAGTATATGCTCCAGCTTCATCAGTTGAGTACCAATGCCAGAACTT 
               
               
                   
               
               
                 GTATCAACTTGAGGGTAACAAGCGAATAACATGTAGAAATGGACAATGGTCAGA 
               
               
                   
               
               
                 ACCACCAAAATGCTTACATCCGTGTGTAATATCCCGAGAAATTATGGAAAATTAT 
               
               
                   
               
               
                 AACATAGCATTAAGGTGGACAGCCAAACAGAAGCTTTATTCGAGAACAGGTGAA 
               
               
                   
               
               
                 TCAGTTGAATTTGTGTGTAAACGGGGATATCGTCTTTCATCACGTTCTCACACATT 
               
               
                   
               
               
                 GCGAACAACATGTTGGGATGGGAAACTGGAGTATCCAACTTGTGCAAAAAGATA 
               
               
                   
               
               
                 GCTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTT 
               
               
                   
               
               
                 GACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCA 
               
               
                   
               
               
                 TCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACA 
               
               
                   
               
               
                 GCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGC 
               
               
                   
               
               
                 TCTATGGGTTAACTCGAGGGATCCCGGACCGAGCGGCCGCAGGAACCCCTAGTG 
               
               
                   
               
               
                 ATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGAC 
               
               
                   
               
               
                 CAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAG 
               
               
                   
               
               
                 CGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG 
               
               
                   
               
               
                 CGGTATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCG 
               
               
                   
               
               
                 CATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCA 
               
               
                   
               
               
                 GCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCC 
               
               
                   
               
               
                 GGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTG 
               
               
                   
               
               
                 CTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGG 
               
               
                   
               
               
                 GCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTA 
               
               
                   
               
               
                 ATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGGCTATTC 
               
               
                   
               
               
                 TTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTG 
               
               
                   
               
               
                 ATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTTTAT 
               
               
                   
               
               
                 GGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACA 
               
               
                   
               
               
                 CCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCT 
               
               
                   
               
               
                 TACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGT 
               
               
                   
               
               
                 CATCACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGT 
               
               
                   
               
               
                 TAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAAT 
               
               
                   
               
               
                 GTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCT 
               
               
                   
               
               
                 CATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTAT 
               
               
                   
               
               
                 GAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCC 
               
               
                   
               
               
                 TGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTG 
               
               
                   
               
               
                 GGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAG 
               
               
                   
               
               
                 AGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTAT 
               
               
                   
               
               
                 GTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCAT 
               
               
                   
               
               
                 ACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTT 
               
               
                   
               
               
                 ACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGAT 
               
               
                   
               
               
                 AACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACC 
               
               
                   
               
               
                 GCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGG 
               
               
                   
               
               
                 AGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAA 
               
               
                   
               
               
                 TGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCG 
               
               
                   
               
               
                 GCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCG 
               
               
                   
               
               
                 CTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGT 
               
               
                   
               
               
                 GGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCG 
               
               
                   
               
               
                 TAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGA 
               
               
                   
               
               
                 TCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTA 
               
               
                   
               
               
                 CTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGG 
               
               
                   
               
               
                 TGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC 
               
               
                   
               
               
                 CACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTT 
               
               
                   
               
               
                 TTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGT 
               
               
                   
               
               
                 TTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGC 
               
               
                   
               
               
                 AGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACT 
               
               
                   
               
               
                 TCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGT 
               
               
                   
               
               
                 GGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAG 
               
               
                   
               
               
                 TTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCC 
               
               
                   
               
               
                 AGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGA 
               
               
                   
               
               
                 GAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGG 
               
               
                   
               
               
                 CAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGT 
               
               
                   
               
               
                 ATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGA 
               
               
                   
               
               
                 TGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTA 
               
               
                   
               
               
                 CGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 10-SV40i Intron 
               
               
                 GTAAGTTTAGTCTTTTTGTCTTTTATTTCAGGTCCCGGATCCGGTGGTGGTGCAAA 
               
               
                   
               
               
                 TCAAAGAACTGCTCCTCAGTGGATGTTGCCTTTACTTCTAGGCCTGTACGGAAGT 
               
               
                   
               
               
                 GTTACTTCTGCTCTAAAAGCTGCGGAATTGTACC CGCGG 
               
               
                   
               
               
                 SEQ ID NO: 11-Representative CFH AAV vector (with EF1a promoter 
               
               
                 and SV40i intron) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCG 
               
               
                   
               
               
                 GGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAG 
               
               
                   
               
               
                 AGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTTAACTAGT 
               
               
                   
               
               
                 GGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCA 
               
               
                   
               
               
                 ATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCG 
               
               
                   
               
               
                 TGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGT 
               
               
                   
               
               
                 AGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACAGGTAAGT 
               
               
                   
               
               
                 TTAGTCTTTTTGTCTTTTATTTCAGGTCCCGGATCCGGTGGTGGTGCAAATCAAAG 
               
               
                   
               
               
                 AACTGCTCCTCAGTGGATGTTGCCTTTACTTCTAGGCCTGTACGGAAGTGTTACTT 
               
               
                   
               
               
                 CTGCTCTAAAAGCTGCGGAATTGTACCCGCGGATCGATAGCTGCAGGCGGCCGC 
               
               
                   
               
               
                 CGCCACCATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTATGGGCTATTTGTG 
               
               
                   
               
               
                 TAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAATACAGAAATTCTGACAG 
               
               
                   
               
               
                 GTTCCTGGTCTGACCAAACATATCCAGAAGGCACCCAGGCTATCTATAAATGCCG 
               
               
                   
               
               
                 CCCTGGATATAGATCTCTTGGAAATGTAATAATGGTATGCAGGAAGGGAGAATG 
               
               
                   
               
               
                 GGTTGCTCTTAATCCATTAAGGAAATGTCAGAAAAGGCCCTGTGGACATCCTGGA 
               
               
                   
               
               
                 GATACTCCTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGT 
               
               
                   
               
               
                 AAAAGCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTAC 
               
               
                   
               
               
                 CGTGAATGTGACACAGATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGA 
               
               
                   
               
               
                 AGTGTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATGG 
               
               
                   
               
               
                 AACCAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGTAACTCAGG 
               
               
                   
               
               
                 CTACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATGGTTTTTGGAG 
               
               
                   
               
               
                 TAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCCCCAGATGTTATAAA 
               
               
                   
               
               
                 TGGATCTCCTATATCTCAGAAGATTATTTATAAGGAGAATGAACGATTTCAATAT 
               
               
                   
               
               
                 AAATGTAACATGGGTTATGAATACAGTGAAAGAGGAGATGCTGTATGCACTGAA 
               
               
                   
               
               
                 TCTGGATGGCGTCCGTTGCCTTCATGTGAAGAAAAATCATGTGATAATCCTTATA 
               
               
                   
               
               
                 TTCCAAATGGTGACTACTCACCTTTAAGGATTAAACACAGAACTGGAGATGAAAT 
               
               
                   
               
               
                 CACGTACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAA 
               
               
                   
               
               
                 ATGCACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGAT 
               
               
                   
               
               
                 TATCCAGACATTAAACATGGAGGTCTATATCATGAGAATATGCGTAGACCATACT 
               
               
                   
               
               
                 TTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACATTTTGAGAC 
               
               
                   
               
               
                 TCCGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGATGGTCGCCA 
               
               
                   
               
               
                 GCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAAATGGATATAATC 
               
               
                   
               
               
                 AAAATTATGGAAGAAAGTTTGTACAGGGTAAATCTATAGACGTTGCCTGCCATCC 
               
               
                   
               
               
                 TGGCTACGCTCTTCCAAAAGCGCAGACCACAGTTACATGTATGGAGAATGGCTG 
               
               
                   
               
               
                 GTCTCCTACTCCCAGATGCATCCGTGTCAAAACATGTTCCAAATCAAGTATAGAT 
               
               
                   
               
               
                 ATTGAGAATGGGTTTATTTCTGAATCTCAGTATACATATGCCTTAAAAGAAAAAG 
               
               
                   
               
               
                 CGAAATATCAATGCAAACTAGGATATGTAACAGCAGATGGTGAAACATCAGGAT 
               
               
                   
               
               
                 CAATTACATGTGGGAAAGATGGATGGTCAGCTCAACCCACGTGCATTAAATCTTG 
               
               
                   
               
               
                 TGATATCCCAGTATTTATGAATGCCAGAACTAAAAATGACTTCACATGGTTTAAG 
               
               
                   
               
               
                 CTGAATGACACATTGGACTATGAATGCCATGATGGTTATGAAAGCAATACTGGA 
               
               
                   
               
               
                 AGCACCACTGGTTCCATAGTGTGTGGTTACAATGGTTGGTCTGATTTACCCATAT 
               
               
                   
               
               
                 GTTATGAAAGAGAATGCGAACTTCCTAAAATAGATGTACACTTAGTTCCTGATCG 
               
               
                   
               
               
                 CAAGAAAGACCAGTATAAAGTTGGAGAGGTGTTGAAATTCTCCTGCAAACCAGG 
               
               
                   
               
               
                 ATTTACAATAGTTGGACCTAATTCCGTTCAGTGCTACCACTTTGGATTGTCTCCTG 
               
               
                   
               
               
                 ACCTCCCAATATGTAAAGAGCAAGTACAATCATGTGGTCCACCTCCTGAACTCCT 
               
               
                   
               
               
                 CAATGGGAATGTTAAGGAAAAAACGAAAGAAGAATATGGACACAGTGAAGTGG 
               
               
                   
               
               
                 TGGAATATTATTGCAATCCTAGATTTCTAATGAAGGGACCTAATAAAATTCAATG 
               
               
                   
               
               
                 TGTTGATGGAGAGTGGACAACTTTACCAGTGTGTATTGTGGAGGAGAGTACCTGT 
               
               
                   
               
               
                 GGAGATATACCTGAACTTGAACATGGCTGGGCCCAGCTTTCTTCCCCTCCTTATT 
               
               
                   
               
               
                 ACTATGGAGATTCAGTGGAATTCAATTGCTCAGAATCATTTACAATGATTGGACA 
               
               
                   
               
               
                 CAGATCAATTACGTGTATTCATGGAGTATGGACCCAACTTCCCCAGTGTGTGGCA 
               
               
                   
               
               
                 ATAGATAAACTTAAGAAGTGCAAATCATCAAATTTAATTATACTTGAGGAACATT 
               
               
                   
               
               
                 TAAAAAACAAGAAGGAATTCGATCATAATTCTAACATAAGGTACAGATGTAGAG 
               
               
                   
               
               
                 GAAAAGAAGGATGGATACACACAGTCTGCATAAATGGAAGATGGGATCCAGAA 
               
               
                   
               
               
                 GTGAACTGCTCAATGGCACAAATACAATTATGCCCACCTCCACCTCAGATTCCCA 
               
               
                   
               
               
                 ATTCTCACAATATGACAACCACACTGAATTATCGGGATGGAGAAAAAGTATCTGT 
               
               
                   
               
               
                 TCTTTGCCAAGAAAATTATCTAATTCAGGAAGGAGAAGAAATTACATGCAAAGA 
               
               
                   
               
               
                 TGGAAGATGGCAGTCAATACCACTCTGTGTTGAAAAAATTCCATGTTCACAACCA 
               
               
                   
               
               
                 CCTCAGATAGAACACGGAACCATTAATTCATCCAGGTCTTCACAAGAAAGTTATG 
               
               
                   
               
               
                 CACATGGGACTAAATTGAGTTATACTTGTGAGGGTGGTTTCAGGATATCTGAAGA 
               
               
                   
               
               
                 AAATGAAACAACATGCTACATGGGAAAATGGAGTTCTCCACCTCAGTGTGAAGG 
               
               
                   
               
               
                 CCTTCCTTGTAAATCTCCACCTGAGATTTCTCATGGTGTTGTAGCTCACATGTCAG 
               
               
                   
               
               
                 ACAGTTATCAGTATGGAGAAGAAGTTACGTACAAATGTTTTGAAGGTTTTGGAAT 
               
               
                   
               
               
                 TGATGGGCCTGCAATTGCAAAATGCTTAGGAGAAAAATGGTCTCACCCTCCATCA 
               
               
                   
               
               
                 TGCATAAAAACAGATTGTCTCAGTTTACCTAGCTTTGAAAATGCCATACCCATGG 
               
               
                   
               
               
                 GAGAGAAGAAGGATGTGTATAAGGCGGGTGAGCAAGTGACTTACACTTGTGCAA 
               
               
                   
               
               
                 CATATTACAAAATGGATGGAGCCAGTAATGTAACATGCATTAATAGCAGATGGA 
               
               
                   
               
               
                 CAGGAAGGCCAACATGCAGAGACACCTCCTGTGTGAATCCGCCCACAGTACAAA 
               
               
                   
               
               
                 ATGCTTATATAGTGTCGAGACAGATGAGTAAATATCCATCTGGTGAGAGAGTAC 
               
               
                   
               
               
                 GTTATCAATGTAGGAGCCCTTATGAAATGTTTGGGGATGAAGAAGTGATGTGTTT 
               
               
                   
               
               
                 AAATGGAAACTGGACGGAACCACCTCAATGCAAAGATTCTACAGGAAAATGTGG 
               
               
                   
               
               
                 GCCCCCTCCACCTATTGACAATGGGGACATTACTTCATTCCCGTTGTCAGTATATG 
               
               
                   
               
               
                 CTCCAGCTTCATCAGTTGAGTACCAATGCCAGAACTTGTATCAACTTGAGGGTAA 
               
               
                   
               
               
                 CAAGCGAATAACATGTAGAAATGGACAATGGTCAGAACCACCAAAATGCTTACA 
               
               
                   
               
               
                 TCCGTGTGTAATATCCCGAGAAATTATGGAAAATTATAACATAGCATTAAGGTGG 
               
               
                   
               
               
                 ACAGCCAAACAGAAGCTTTATTCGAGAACAGGTGAATCAGTTGAATTTGTGTGTA 
               
               
                   
               
               
                 AACGGGGATATCGTCTTTCATCACGTTCTCACACATTGCGAACAACATGTTGGGA 
               
               
                   
               
               
                 TGGGAAACTGGAGTATCCAACTTGTGCAAAAAGATAGCTGTGCCTTCTAGTTGCC 
               
               
                   
               
               
                 AGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACT 
               
               
                   
               
               
                 CCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGT 
               
               
                   
               
               
                 GTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGG 
               
               
                   
               
               
                 AAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGGTTAACTCGAGG 
               
               
                   
               
               
                 GATCCCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCT 
               
               
                   
               
               
                 CTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCC 
               
               
                   
               
               
                 GGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGG 
               
               
                   
               
               
                 GCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATAC 
               
               
                   
               
               
                 GTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT 
               
               
                   
               
               
                 GGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCT 
               
               
                   
               
               
                 TTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTA 
               
               
                   
               
               
                 AATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCA 
               
               
                   
               
               
                 AAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGT 
               
               
                   
               
               
                 TTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAA 
               
               
                   
               
               
                 CTGGAACAACACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTG 
               
               
                   
               
               
                 CCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGA 
               
               
                   
               
               
                 ATTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGC 
               
               
                   
               
               
                 TCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGC 
               
               
                   
               
               
                 CCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTC 
               
               
                   
               
               
                 CGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGAGACG 
               
               
                   
               
               
                 AAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTT 
               
               
                   
               
               
                 TCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTT 
               
               
                   
               
               
                 TATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATA 
               
               
                   
               
               
                 AATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTC 
               
               
                   
               
               
                 GCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACG 
               
               
                   
               
               
                 CTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATC 
               
               
                   
               
               
                 GAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTT 
               
               
                   
               
               
                 TTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATT 
               
               
                   
               
               
                 GACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTG 
               
               
                   
               
               
                 GTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGA 
               
               
                   
               
               
                 GAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTC 
               
               
                   
               
               
                 TGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGG 
               
               
                   
               
               
                 ATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAA 
               
               
                   
               
               
                 ACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAAC 
               
               
                   
               
               
                 TATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGAT 
               
               
                   
               
               
                 GGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGG 
               
               
                   
               
               
                 TTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAG 
               
               
                   
               
               
                 CACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGA 
               
               
                   
               
               
                 GTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCAC 
               
               
                   
               
               
                 TGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGA 
               
               
                   
               
               
                 TTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATC 
               
               
                   
               
               
                 TCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGT 
               
               
                   
               
               
                 AGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCT 
               
               
                   
               
               
                 TGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGC 
               
               
                   
               
               
                 TACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATAC 
               
               
                   
               
               
                 TGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCG 
               
               
                   
               
               
                 CCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATA 
               
               
                   
               
               
                 AGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGC 
               
               
                   
               
               
                 GGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCT 
               
               
                   
               
               
                 ACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCG 
               
               
                   
               
               
                 AAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAG 
               
               
                   
               
               
                 CGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGT 
               
               
                   
               
               
                 TTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAG 
               
               
                   
               
               
                 CCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGG 
               
               
                   
               
               
                 CCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 12-HSP7 Promoter 
               
               
                 ACTAGTCCTGCAGGGCCGCCCACTCCCCCTTCCTCTCAGGGTCCCTGTCCCCTCCA 
               
               
                   
               
               
                 GTGAATCCCAGAAGACTCTGGAGAGTTCTGAGCAGGGGGCGGCACTCTGGCCTC 
               
               
                   
               
               
                 TGATTGGTCCAAGGAAGGCTGGGGGGCAGGACGGGAGGCGAAAACCCTGGAAT 
               
               
                   
               
               
                 ATTCCCGACCTGGCAGCCTCATCGAGCTCGGTGATTGGCTCAGAAGGGAAAAGG 
               
               
                   
               
               
                 CGGGTCTCCGTGACGACTTATAAAAGCCCAGGGGCAAGCGGTCCGGATAACGGC 
               
               
                   
               
               
                 TAGCCTGAGGAGCTGCTGCGACAGTCCACTACCTTTTTCGAGAGTGACTCCCGTT 
               
               
                   
               
               
                 GTCCCAAGGCTTCCCAGAGCGAACCTGTGCGGCTGCAGGCACCGGCGCGTCGAG 
               
               
                   
               
               
                 TTTCCGGCGTCCGGAAGGACCGAGCTCTTCTCGCGGATCCAGTGTTCCGTTTCCA 
               
               
                   
               
               
                 GCCCCCAATCTCAGAGCGGAGCCGACAGAGAGCAGGGAACC 
               
               
                   
               
               
                 SEQ ID NO: 13-Representative CFH AAV Vector (with HSP70 Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCG 
               
               
                   
               
               
                 GGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAG 
               
               
                   
               
               
                 AGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCGTTAACTAGTCCTG 
               
               
                   
               
               
                 CAGGGCCGCCCACTCCCCCTTCCTCTCAGGGTCCCTGTCCCCTCCAGTGAATCCC 
               
               
                   
               
               
                 AGAAGACTCTGGAGAGTTCTGAGCAGGGGGCGGCACTCTGGCCTCTGATTGGTC 
               
               
                   
               
               
                 CAAGGAAGGCTGGGGGGCAGGACGGGAGGCGAAAACCCTGGAATATTCCCGAC 
               
               
                   
               
               
                 CTGGCAGCCTCATCGAGCTCGGTGATTGGCTCAGAAGGGAAAAGGCGGGTCTCC 
               
               
                   
               
               
                 GTGACGACTTATAAAAGCCCAGGGGCAAGCGGTCCGGATAACGGCTAGCCTGAG 
               
               
                   
               
               
                 GAGCTGCTGCGACAGTCCACTACCTTTTTCGAGAGTGACTCCCGTTGTCCCAAGG 
               
               
                   
               
               
                 CTTCCCAGAGCGAACCTGTGCGGCTGCAGGCACCGGCGCGTCGAGTTTCCGGCGT 
               
               
                   
               
               
                 CCGGAAGGACCGAGCTCTTCTCGCGGATCCAGTGTTCCGTTTCCAGCCCCCAATC 
               
               
                   
               
               
                 TCAGAGCGGAGCCGACAGAGAGCAGGGAACCCTGCAGATCGATGCGGCCGCACC 
               
               
                   
               
               
                 ATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTATGGGCTATTTGTGTAGCAG 
               
               
                   
               
               
                 AAGATTGCAATGAACTTCCTCCAAGAAGAAATACAGAAATTCTGACAGGTTCCT 
               
               
                   
               
               
                 GGTCTGACCAAACATATCCAGAAGGCACCCAGGCTATCTATAAATGCCGCCCTG 
               
               
                   
               
               
                 GATATAGATCTCTTGGAAATGTAATAATGGTATGCAGGAAGGGAGAATGGGTTG 
               
               
                   
               
               
                 CTCTTAATCCATTAAGGAAATGTCAGAAAAGGCCCTGTGGACATCCTGGAGATAC 
               
               
                   
               
               
                 TCCTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGTAAAA 
               
               
                   
               
               
                 GCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTACCGTG 
               
               
                   
               
               
                 AATGTGACACAGATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGAAGTG 
               
               
                   
               
               
                 TTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATGGAACC 
               
               
                   
               
               
                 AGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGTAACTCAGGCTAC 
               
               
                   
               
               
                 AAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATGGTTTTTGGAGTAAA 
               
               
                   
               
               
                 GAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCCCCAGATGTTATAAATGGA 
               
               
                   
               
               
                 TCTCCTATATCTCAGAAGATTATTTATAAGGAGAATGAACGATTTCAATATAAAT 
               
               
                   
               
               
                 GTAACATGGGTTATGAATACAGTGAAAGAGGAGATGCTGTATGCACTGAATCTG 
               
               
                   
               
               
                 GATGGCGTCCGTTGCCTTCATGTGAAGAAAAATCATGTGATAATCCTTATATTCC 
               
               
                   
               
               
                 AAATGGTGACTACTCACCTTTAAGGATTAAACACAGAACTGGAGATGAAATCAC 
               
               
                   
               
               
                 GTACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAAATG 
               
               
                   
               
               
                 CACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGATTAT 
               
               
                   
               
               
                 CCAGACATTAAACATGGAGGTCTATATCATGAGAATATGCGTAGACCATACTTTC 
               
               
                   
               
               
                 CAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACATTTTGAGACTCC 
               
               
                   
               
               
                 GTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGATGGTCGCCAGC 
               
               
                   
               
               
                 AGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAAATGGATATAATCAA 
               
               
                   
               
               
                 AATTATGGAAGAAAGTTTGTACAGGGTAAATCTATAGACGTTGCCTGCCATCCTG 
               
               
                   
               
               
                 GCTACGCTCTTCCAAAAGCGCAGACCACAGTTACATGTATGGAGAATGGCTGGTC 
               
               
                   
               
               
                 TCCTACTCCCAGATGCATCCGTGTCAAAACATGTTCCAAATCAAGTATAGATATT 
               
               
                   
               
               
                 GAGAATGGGTTTATTTCTGAATCTCAGTATACATATGCCTTAAAAGAAAAAGCGA 
               
               
                   
               
               
                 AATATCAATGCAAACTAGGATATGTAACAGCAGATGGTGAAACATCAGGATCAA 
               
               
                   
               
               
                 TTACATGTGGGAAAGATGGATGGTCAGCTCAACCCACGTGCATTAAATCTTGTGA 
               
               
                   
               
               
                 TATCCCAGTATTTATGAATGCCAGAACTAAAAATGACTTCACATGGTTTAAGCTG 
               
               
                   
               
               
                 AATGACACATTGGACTATGAATGCCATGATGGTTATGAAAGCAATACTGGAAGC 
               
               
                   
               
               
                 ACCACTGGTTCCATAGTGTGTGGTTACAATGGTTGGTCTGATTTACCCATATGTTA 
               
               
                   
               
               
                 TGAAAGAGAATGCGAACTTCCTAAAATAGATGTACACTTAGTTCCTGATCGCAAG 
               
               
                   
               
               
                 AAAGACCAGTATAAAGTTGGAGAGGTGTTGAAATTCTCCTGCAAACCAGGATTT 
               
               
                   
               
               
                 ACAATAGTTGGACCTAATTCCGTTCAGTGCTACCACTTTGGATTGTCTCCTGACCT 
               
               
                   
               
               
                 CCCAATATGTAAAGAGCAAGTACAATCATGTGGTCCACCTCCTGAACTCCTCAAT 
               
               
                   
               
               
                 GGGAATGTTAAGGAAAAAACGAAAGAAGAATATGGACACAGTGAAGTGGTGGA 
               
               
                   
               
               
                 ATATTATTGCAATCCTAGATTTCTAATGAAGGGACCTAATAAAATTCAATGTGTT 
               
               
                   
               
               
                 GATGGAGAGTGGACAACTTTACCAGTGTGTATTGTGGAGGAGAGTACCTGTGGA 
               
               
                   
               
               
                 GATATACCTGAACTTGAACATGGCTGGGCCCAGCTTTCTTCCCCTCCTTATTACTA 
               
               
                   
               
               
                 TGGAGATTCAGTGGAATTCAATTGCTCAGAATCATTTACAATGATTGGACACAGA 
               
               
                   
               
               
                 TCAATTACGTGTATTCATGGAGTATGGACCCAACTTCCCCAGTGTGTGGCAATAG 
               
               
                   
               
               
                 ATAAACTTAAGAAGTGCAAATCATCAAATTTAATTATACTTGAGGAACATTTAAA 
               
               
                   
               
               
                 AAACAAGAAGGAATTCGATCATAATTCTAACATAAGGTACAGATGTAGAGGAAA 
               
               
                   
               
               
                 AGAAGGATGGATACACACAGTCTGCATAAATGGAAGATGGGATCCAGAAGTGAA 
               
               
                   
               
               
                 CTGCTCAATGGCACAAATACAATTATGCCCACCTCCACCTCAGATTCCCAATTCT 
               
               
                   
               
               
                 CACAATATGACAACCACACTGAATTATCGGGATGGAGAAAAAGTATCTGTTCTTT 
               
               
                   
               
               
                 GCCAAGAAAATTATCTAATTCAGGAAGGAGAAGAAATTACATGCAAAGATGGAA 
               
               
                   
               
               
                 GATGGCAGTCAATACCACTCTGTGTTGAAAAAATTCCATGTTCACAACCACCTCA 
               
               
                   
               
               
                 GATAGAACACGGAACCATTAATTCATCCAGGTCTTCACAAGAAAGTTATGCACAT 
               
               
                   
               
               
                 GGGACTAAATTGAGTTATACTTGTGAGGGTGGTTTCAGGATATCTGAAGAAAATG 
               
               
                   
               
               
                 AAACAACATGCTACATGGGAAAATGGAGTTCTCCACCTCAGTGTGAAGGCCTTCC 
               
               
                   
               
               
                 TTGTAAATCTCCACCTGAGATTTCTCATGGTGTTGTAGCTCACATGTCAGACAGTT 
               
               
                   
               
               
                 ATCAGTATGGAGAAGAAGTTACGTACAAATGTTTTGAAGGTTTTGGAATTGATGG 
               
               
                   
               
               
                 GCCTGCAATTGCAAAATGCTTAGGAGAAAAATGGTCTCACCCTCCATCATGCATA 
               
               
                   
               
               
                 AAAACAGATTGTCTCAGTTTACCTAGCTTTGAAAATGCCATACCCATGGGAGAGA 
               
               
                   
               
               
                 AGAAGGATGTGTATAAGGCGGGTGAGCAAGTGACTTACACTTGTGCAACATATT 
               
               
                   
               
               
                 ACAAAATGGATGGAGCCAGTAATGTAACATGCATTAATAGCAGATGGACAGGAA 
               
               
                   
               
               
                 GGCCAACATGCAGAGACACCTCCTGTGTGAATCCGCCCACAGTACAAAATGCTT 
               
               
                   
               
               
                 ATATAGTGTCGAGACAGATGAGTAAATATCCATCTGGTGAGAGAGTACGTTATC 
               
               
                   
               
               
                 AATGTAGGAGCCCTTATGAAATGTTTGGGGATGAAGAAGTGATGTGTTTAAATG 
               
               
                   
               
               
                 GAAACTGGACGGAACCACCTCAATGCAAAGATTCTACAGGAAAATGTGGGCCCC 
               
               
                   
               
               
                 CTCCACCTATTGACAATGGGGACATTACTTCATTCCCGTTGTCAGTATATGCTCCA 
               
               
                   
               
               
                 GCTTCATCAGTTGAGTACCAATGCCAGAACTTGTATCAACTTGAGGGTAACAAGC 
               
               
                   
               
               
                 GAATAACATGTAGAAATGGACAATGGTCAGAACCACCAAAATGCTTACATCCGT 
               
               
                   
               
               
                 GTGTAATATCCCGAGAAATTATGGAAAATTATAACATAGCATTAAGGTGGACAG 
               
               
                   
               
               
                 CCAAACAGAAGCTTTATTCGAGAACAGGTGAATCAGTTGAATTTGTGTGTAAACG 
               
               
                   
               
               
                 GGGATATCGTCTTTCATCACGTTCTCACACATTGCGAACAACATGTTGGGATGGG 
               
               
                   
               
               
                 AAACTGGAGTATCCAACTTGTGCAAAAAGATAGCTGTGCCTTCTAGTTGCCAGCC 
               
               
                   
               
               
                 ATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCA 
               
               
                   
               
               
                 CTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCA 
               
               
                   
               
               
                 TTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGA 
               
               
                   
               
               
                 CAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGGTTAACTCGAGGGATC 
               
               
                   
               
               
                 CCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTG 
               
               
                   
               
               
                 CGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGC 
               
               
                   
               
               
                 TTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGGCGC 
               
               
                   
               
               
                 CTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATACGTCA 
               
               
                   
               
               
                 AAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTG 
               
               
                   
               
               
                 GTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCG 
               
               
                   
               
               
                 CTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATC 
               
               
                   
               
               
                 GGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAA 
               
               
                   
               
               
                 ACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTT 
               
               
                   
               
               
                 CGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGG 
               
               
                   
               
               
                 AACAACACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGA 
               
               
                   
               
               
                 TTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTT 
               
               
                   
               
               
                 TAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG 
               
               
                   
               
               
                 ATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCT 
               
               
                   
               
               
                 GACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGG 
               
               
                   
               
               
                 GAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGAGACGAAA 
               
               
                   
               
               
                 GGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTT 
               
               
                   
               
               
                 AGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATT 
               
               
                   
               
               
                 TTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATG 
               
               
                   
               
               
                 CTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCC 
               
               
                   
               
               
                 TTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGG 
               
               
                   
               
               
                 TGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAAC 
               
               
                   
               
               
                 TGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCC 
               
               
                   
               
               
                 AATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGAC 
               
               
                   
               
               
                 GCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTG 
               
               
                   
               
               
                 AGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAAT 
               
               
                   
               
               
                 TATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGAC 
               
               
                   
               
               
                 AACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCA 
               
               
                   
               
               
                 TGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGA 
               
               
                   
               
               
                 CGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATT 
               
               
                   
               
               
                 AACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAG 
               
               
                   
               
               
                 GCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTA 
               
               
                   
               
               
                 TTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACT 
               
               
                   
               
               
                 GGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCA 
               
               
                   
               
               
                 GGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGAT 
               
               
                   
               
               
                 TAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTA 
               
               
                   
               
               
                 AAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCAT 
               
               
                   
               
               
                 GACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAA 
               
               
                   
               
               
                 AAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCA 
               
               
                   
               
               
                 AACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACC 
               
               
                   
               
               
                 AACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTC 
               
               
                   
               
               
                 CTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTA 
               
               
                   
               
               
                 CATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTC 
               
               
                   
               
               
                 GTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTC 
               
               
                   
               
               
                 GGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACAC 
               
               
                   
               
               
                 CGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGG 
               
               
                   
               
               
                 GAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCA 
               
               
                   
               
               
                 CGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCG 
               
               
                   
               
               
                 CCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTA 
               
               
                   
               
               
                 TGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTT 
               
               
                   
               
               
                 TTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 14-sCBA Promoter 
               
               
                 ACTAGTCCCCACGTTCTGCTTCACTCTCCCCATCTCCCCCCCCTCCCCACCCCCAA 
               
               
                   
               
               
                 TTTTGTATTTATTTATTTTTTAATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGG 
               
               
                   
               
               
                 GGGGGGCGCGCGCCAGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGAG 
               
               
                   
               
               
                 GCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCCGAAAGTTTCCTTT 
               
               
                   
               
               
                 TATGGCGAGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGGCGGG 
               
               
                   
               
               
                 SEQ ID NO: 15-Representative CFH AAV Vector (with sCBA Promoter 
               
               
                 and SV40i Intron) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCG 
               
               
                   
               
               
                 GGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAG 
               
               
                   
               
               
                 AGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTTAACTAGT 
               
               
                   
               
               
                 CCCCACGTTCTGCTTCACTCTCCCCATCTCCCCCCCCTCCCCACCCCCAATTTTGT 
               
               
                   
               
               
                 ATTTATTTATTTTTTAATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGG 
               
               
                   
               
               
                 GCGCGCGCCAGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGAGGCGGA 
               
               
                   
               
               
                 GAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGG 
               
               
                   
               
               
                 CGAGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGGCGGGGTAAG 
               
               
                   
               
               
                 TTTAGTCTTTTTGTCTTTTATTTCAGGTCCCGGATCCGGTGGTGGTGCAAATCAAA 
               
               
                   
               
               
                 GAACTGCTCCTCAGTGGATGTTGCCTTTACTTCTAGGCCTGTACGGAAGTGTTACT 
               
               
                   
               
               
                 TCTGCTCTAAAAGCTGCGGAATTGTACCCGCGGATCGATAGCTGCAGGCGGCCGC 
               
               
                   
               
               
                 CGCCACCATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTATGGGCTATTTGTG 
               
               
                   
               
               
                 TAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAATACAGAAATTCTGACAG 
               
               
                   
               
               
                 GTTCCTGGTCTGACCAAACATATCCAGAAGGCACCCAGGCTATCTATAAATGCCG 
               
               
                   
               
               
                 CCCTGGATATAGATCTCTTGGAAATGTAATAATGGTATGCAGGAAGGGAGAATG 
               
               
                   
               
               
                 GGTTGCTCTTAATCCATTAAGGAAATGTCAGAAAAGGCCCTGTGGACATCCTGGA 
               
               
                   
               
               
                 GATACTCCTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGT 
               
               
                   
               
               
                 AAAAGCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTAC 
               
               
                   
               
               
                 CGTGAATGTGACACAGATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGA 
               
               
                   
               
               
                 AGTGTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATGG 
               
               
                   
               
               
                 AACCAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGTAACTCAGG 
               
               
                   
               
               
                 CTACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATGGTTTTTGGAG 
               
               
                   
               
               
                 TAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCCCCAGATGTTATAAA 
               
               
                   
               
               
                 TGGATCTCCTATATCTCAGAAGATTATTTATAAGGAGAATGAACGATTTCAATAT 
               
               
                   
               
               
                 AAATGTAACATGGGTTATGAATACAGTGAAAGAGGAGATGCTGTATGCACTGAA 
               
               
                   
               
               
                 TCTGGATGGCGTCCGTTGCCTTCATGTGAAGAAAAATCATGTGATAATCCTTATA 
               
               
                   
               
               
                 TTCCAAATGGTGACTACTCACCTTTAAGGATTAAACACAGAACTGGAGATGAAAT 
               
               
                   
               
               
                 CACGTACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAA 
               
               
                   
               
               
                 ATGCACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGAT 
               
               
                   
               
               
                 TATCCAGACATTAAACATGGAGGTCTATATCATGAGAATATGCGTAGACCATACT 
               
               
                   
               
               
                 TTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACATTTTGAGAC 
               
               
                   
               
               
                 TCCGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGATGGTCGCCA 
               
               
                   
               
               
                 GCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAAATGGATATAATC 
               
               
                   
               
               
                 AAAATTATGGAAGAAAGTTTGTACAGGGTAAATCTATAGACGTTGCCTGCCATCC 
               
               
                   
               
               
                 TGGCTACGCTCTTCCAAAAGCGCAGACCACAGTTACATGTATGGAGAATGGCTG 
               
               
                   
               
               
                 GTCTCCTACTCCCAGATGCATCCGTGTCAAAACATGTTCCAAATCAAGTATAGAT 
               
               
                   
               
               
                 ATTGAGAATGGGTTTATTTCTGAATCTCAGTATACATATGCCTTAAAAGAAAAAG 
               
               
                   
               
               
                 CGAAATATCAATGCAAACTAGGATATGTAACAGCAGATGGTGAAACATCAGGAT 
               
               
                   
               
               
                 CAATTACATGTGGGAAAGATGGATGGTCAGCTCAACCCACGTGCATTAAATCTTG 
               
               
                   
               
               
                 TGATATCCCAGTATTTATGAATGCCAGAACTAAAAATGACTTCACATGGTTTAAG 
               
               
                   
               
               
                 CTGAATGACACATTGGACTATGAATGCCATGATGGTTATGAAAGCAATACTGGA 
               
               
                   
               
               
                 AGCACCACTGGTTCCATAGTGTGTGGTTACAATGGTTGGTCTGATTTACCCATAT 
               
               
                   
               
               
                 GTTATGAAAGAGAATGCGAACTTCCTAAAATAGATGTACACTTAGTTCCTGATCG 
               
               
                   
               
               
                 CAAGAAAGACCAGTATAAAGTTGGAGAGGTGTTGAAATTCTCCTGCAAACCAGG 
               
               
                   
               
               
                 ATTTACAATAGTTGGACCTAATTCCGTTCAGTGCTACCACTTTGGATTGTCTCCTG 
               
               
                   
               
               
                 ACCTCCCAATATGTAAAGAGCAAGTACAATCATGTGGTCCACCTCCTGAACTCCT 
               
               
                   
               
               
                 CAATGGGAATGTTAAGGAAAAAACGAAAGAAGAATATGGACACAGTGAAGTGG 
               
               
                   
               
               
                 TGGAATATTATTGCAATCCTAGATTTCTAATGAAGGGACCTAATAAAATTCAATG 
               
               
                   
               
               
                 TGTTGATGGAGAGTGGACAACTTTACCAGTGTGTATTGTGGAGGAGAGTACCTGT 
               
               
                   
               
               
                 GGAGATATACCTGAACTTGAACATGGCTGGGCCCAGCTTTCTTCCCCTCCTTATT 
               
               
                   
               
               
                 ACTATGGAGATTCAGTGGAATTCAATTGCTCAGAATCATTTACAATGATTGGACA 
               
               
                   
               
               
                 CAGATCAATTACGTGTATTCATGGAGTATGGACCCAACTTCCCCAGTGTGTGGCA 
               
               
                   
               
               
                 ATAGATAAACTTAAGAAGTGCAAATCATCAAATTTAATTATACTTGAGGAACATT 
               
               
                   
               
               
                 TAAAAAACAAGAAGGAATTCGATCATAATTCTAACATAAGGTACAGATGTAGAG 
               
               
                   
               
               
                 GAAAAGAAGGATGGATACACACAGTCTGCATAAATGGAAGATGGGATCCAGAA 
               
               
                   
               
               
                 GTGAACTGCTCAATGGCACAAATACAATTATGCCCACCTCCACCTCAGATTCCCA 
               
               
                   
               
               
                 ATTCTCACAATATGACAACCACACTGAATTATCGGGATGGAGAAAAAGTATCTGT 
               
               
                   
               
               
                 TCTTTGCCAAGAAAATTATCTAATTCAGGAAGGAGAAGAAATTACATGCAAAGA 
               
               
                   
               
               
                 TGGAAGATGGCAGTCAATACCACTCTGTGTTGAAAAAATTCCATGTTCACAACCA 
               
               
                   
               
               
                 CCTCAGATAGAACACGGAACCATTAATTCATCCAGGTCTTCACAAGAAAGTTATG 
               
               
                   
               
               
                 CACATGGGACTAAATTGAGTTATACTTGTGAGGGTGGTTTCAGGATATCTGAAGA 
               
               
                   
               
               
                 AAATGAAACAACATGCTACATGGGAAAATGGAGTTCTCCACCTCAGTGTGAAGG 
               
               
                   
               
               
                 CCTTCCTTGTAAATCTCCACCTGAGATTTCTCATGGTGTTGTAGCTCACATGTCAG 
               
               
                   
               
               
                 ACAGTTATCAGTATGGAGAAGAAGTTACGTACAAATGTTTTGAAGGTTTTGGAAT 
               
               
                   
               
               
                 TGATGGGCCTGCAATTGCAAAATGCTTAGGAGAAAAATGGTCTCACCCTCCATCA 
               
               
                   
               
               
                 TGCATAAAAACAGATTGTCTCAGTTTACCTAGCTTTGAAAATGCCATACCCATGG 
               
               
                   
               
               
                 GAGAGAAGAAGGATGTGTATAAGGCGGGTGAGCAAGTGACTTACACTTGTGCAA 
               
               
                   
               
               
                 CATATTACAAAATGGATGGAGCCAGTAATGTAACATGCATTAATAGCAGATGGA 
               
               
                   
               
               
                 CAGGAAGGCCAACATGCAGAGACACCTCCTGTGTGAATCCGCCCACAGTACAAA 
               
               
                   
               
               
                 ATGCTTATATAGTGTCGAGACAGATGAGTAAATATCCATCTGGTGAGAGAGTAC 
               
               
                   
               
               
                 GTTATCAATGTAGGAGCCCTTATGAAATGTTTGGGGATGAAGAAGTGATGTGTTT 
               
               
                   
               
               
                 AAATGGAAACTGGACGGAACCACCTCAATGCAAAGATTCTACAGGAAAATGTGG 
               
               
                   
               
               
                 GCCCCCTCCACCTATTGACAATGGGGACATTACTTCATTCCCGTTGTCAGTATATG 
               
               
                   
               
               
                 CTCCAGCTTCATCAGTTGAGTACCAATGCCAGAACTTGTATCAACTTGAGGGTAA 
               
               
                   
               
               
                 CAAGCGAATAACATGTAGAAATGGACAATGGTCAGAACCACCAAAATGCTTACA 
               
               
                   
               
               
                 TCCGTGTGTAATATCCCGAGAAATTATGGAAAATTATAACATAGCATTAAGGTGG 
               
               
                   
               
               
                 ACAGCCAAACAGAAGCTTTATTCGAGAACAGGTGAATCAGTTGAATTTGTGTGTA 
               
               
                   
               
               
                 AACGGGGATATCGTCTTTCATCACGTTCTCACACATTGCGAACAACATGTTGGGA 
               
               
                   
               
               
                 TGGGAAACTGGAGTATCCAACTTGTGCAAAAAGATAGCTGTGCCTTCTAGTTGCC 
               
               
                   
               
               
                 AGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACT 
               
               
                   
               
               
                 CCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGT 
               
               
                   
               
               
                 GTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGG 
               
               
                   
               
               
                 AAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGGTTAACTCGAGG 
               
               
                   
               
               
                 GATCCCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCT 
               
               
                   
               
               
                 CTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCC 
               
               
                   
               
               
                 GGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGG 
               
               
                   
               
               
                 GCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATAC 
               
               
                   
               
               
                 GTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT 
               
               
                   
               
               
                 GGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCT 
               
               
                   
               
               
                 TTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTA 
               
               
                   
               
               
                 AATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCA 
               
               
                   
               
               
                 AAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGT 
               
               
                   
               
               
                 TTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAA 
               
               
                   
               
               
                 CTGGAACAACACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTG 
               
               
                   
               
               
                 CCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGA 
               
               
                   
               
               
                 ATTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGC 
               
               
                   
               
               
                 TCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGC 
               
               
                   
               
               
                 CCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTC 
               
               
                   
               
               
                 CGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGAGACG 
               
               
                   
               
               
                 AAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTT 
               
               
                   
               
               
                 TCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTT 
               
               
                   
               
               
                 TATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATA 
               
               
                   
               
               
                 AATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTC 
               
               
                   
               
               
                 GCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACG 
               
               
                   
               
               
                 CTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATC 
               
               
                   
               
               
                 GAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTT 
               
               
                   
               
               
                 TTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATT 
               
               
                   
               
               
                 GACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTG 
               
               
                   
               
               
                 GTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGA 
               
               
                   
               
               
                 GAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTC 
               
               
                   
               
               
                 TGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGG 
               
               
                   
               
               
                 ATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAA 
               
               
                   
               
               
                 ACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAAC 
               
               
                   
               
               
                 TATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGAT 
               
               
                   
               
               
                 GGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGG 
               
               
                   
               
               
                 TTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAG 
               
               
                   
               
               
                 CACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGA 
               
               
                   
               
               
                 GTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCAC 
               
               
                   
               
               
                 TGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGA 
               
               
                   
               
               
                 TTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATC 
               
               
                   
               
               
                 TCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGT 
               
               
                   
               
               
                 AGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCT 
               
               
                   
               
               
                 TGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGC 
               
               
                   
               
               
                 TACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATAC 
               
               
                   
               
               
                 TGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCG 
               
               
                   
               
               
                 CCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATA 
               
               
                   
               
               
                 AGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGC 
               
               
                   
               
               
                 GGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCT 
               
               
                   
               
               
                 ACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCG 
               
               
                   
               
               
                 AAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAG 
               
               
                   
               
               
                 CGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGT 
               
               
                   
               
               
                 TTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAG 
               
               
                   
               
               
                 CCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGG 
               
               
                   
               
               
                 CCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 16-hAAT1 Promoter 
               
               
                 GTTAACGGCTGCCCACTGGGCATTTCATAGGTGGCTCAGTCCTCTTCCCTCTGCA 
               
               
                   
               
               
                 GCTGGCCCCAGAAACCTGCCAGTTATTGGTGCCAGGTCTGTGCCAGGAGGGCGA 
               
               
                   
               
               
                 GGCCTGTCATTTCTAGTAATCCTCTGGGCAGTGTGACTGTACCTCTTGCGGCAACT 
               
               
                   
               
               
                 CAAAGGGAGAGGGTGACTTGTCCCGGGTCACAGAGCTGAAAGGGCAGGTACAAC 
               
               
                   
               
               
                 AGGTGACATGCCGGGCTGTCTGAGTTTATGAGGGCCCAGTCTTGTGTCTGCCGGG 
               
               
                   
               
               
                 CAATGAGCAAGGCTCCTTCCTGTCCAAGCTCCCCGCCCCTCCCCAGCCTACTGCC 
               
               
                   
               
               
                 TCCACCCGAAGTCTACTTCCTGGG 
               
               
                   
               
               
                 SEQ ID NO: 17-Representative CFH AAV Vector (with hAAT1 promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCG 
               
               
                   
               
               
                 GGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAG 
               
               
                   
               
               
                 AGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTGTTAACG 
               
               
                   
               
               
                 GCTGCCCACTGGGCATTTCATAGGTGGCTCAGTCCTCTTCCCTCTGCAGCTGGCCC 
               
               
                   
               
               
                 CAGAAACCTGCCAGTTATTGGTGCCAGGTCTGTGCCAGGAGGGCGAGGCCTGTC 
               
               
                   
               
               
                 ATTTCTAGTAATCCTCTGGGCAGTGTGACTGTACCTCTTGCGGCAACTCAAAGGG 
               
               
                   
               
               
                 AGAGGGTGACTTGTCCCGGGTCACAGAGCTGAAAGGGCAGGTACAACAGGTGAC 
               
               
                   
               
               
                 ATGCCGGGCTGTCTGAGTTTATGAGGGCCCAGTCTTGTGTCTGCCGGGCAATGAG 
               
               
                   
               
               
                 CAAGGCTCCTTCCTGTCCAAGCTCCCCGCCCCTCCCCAGCCTACTGCCTCCACCCG 
               
               
                   
               
               
                 AAGTCTACTTCCTGGGATCGATAGCTGCAGGCGGCCGCCGCCACCATGAGACTTC 
               
               
                   
               
               
                 TAGCAAAGATTATTTGCCTTATGTTATGGGCTATTTGTGTAGCAGAAGATTGCAA 
               
               
                   
               
               
                 TGAACTTCCTCCAAGAAGAAATACAGAAATTCTGACAGGTTCCTGGTCTGACCAA 
               
               
                   
               
               
                 ACATATCCAGAAGGCACCCAGGCTATCTATAAATGCCGCCCTGGATATAGATCTC 
               
               
                   
               
               
                 TTGGAAATGTAATAATGGTATGCAGGAAGGGAGAATGGGTTGCTCTTAATCCATT 
               
               
                   
               
               
                 AAGGAAATGTCAGAAAAGGCCCTGTGGACATCCTGGAGATACTCCTTTTGGTACT 
               
               
                   
               
               
                 TTTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGTAAAAGCTGTGTATACAT 
               
               
                   
               
               
                 GTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTACCGTGAATGTGACACAG 
               
               
                   
               
               
                 ATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGAAGTGTTTACCAGTGAC 
               
               
                   
               
               
                 AGCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATGGAACCAGATCGGGAATA 
               
               
                   
               
               
                 CCATTTTGGACAAGCAGTACGGTTTGTATGTAACTCAGGCTACAAGATTGAAGGA 
               
               
                   
               
               
                 GATGAAGAAATGCATTGTTCAGACGATGGTTTTTGGAGTAAAGAGAAACCAAAG 
               
               
                   
               
               
                 TGTGTGGAAATTTCATGCAAATCCCCAGATGTTATAAATGGATCTCCTATATCTC 
               
               
                   
               
               
                 AGAAGATTATTTATAAGGAGAATGAACGATTTCAATATAAATGTAACATGGGTT 
               
               
                   
               
               
                 ATGAATACAGTGAAAGAGGAGATGCTGTATGCACTGAATCTGGATGGCGTCCGT 
               
               
                   
               
               
                 TGCCTTCATGTGAAGAAAAATCATGTGATAATCCTTATATTCCAAATGGTGACTA 
               
               
                   
               
               
                 CTCACCTTTAAGGATTAAACACAGAACTGGAGATGAAATCACGTACCAGTGTAG 
               
               
                   
               
               
                 AAATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAAATGCACAAGTACTGG 
               
               
                   
               
               
                 CTGGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGATTATCCAGACATTAAA 
               
               
                   
               
               
                 CATGGAGGTCTATATCATGAGAATATGCGTAGACCATACTTTCCAGTAGCTGTAG 
               
               
                   
               
               
                 GAAAATATTACTCCTATTACTGTGATGAACATTTTGAGACTCCGTCAGGAAGTTA 
               
               
                   
               
               
                 CTGGGATCACATTCATTGCACACAAGATGGATGGTCGCCAGCAGTACCATGCCTC 
               
               
                   
               
               
                 AGAAAATGTTATTTTCCTTATTTGGAAAATGGATATAATCAAAATTATGGAAGAA 
               
               
                   
               
               
                 AGTTTGTACAGGGTAAATCTATAGACGTTGCCTGCCATCCTGGCTACGCTCTTCC 
               
               
                   
               
               
                 AAAAGCGCAGACCACAGTTACATGTATGGAGAATGGCTGGTCTCCTACTCCCAG 
               
               
                   
               
               
                 ATGCATCCGTGTCAAAACATGTTCCAAATCAAGTATAGATATTGAGAATGGGTTT 
               
               
                   
               
               
                 ATTTCTGAATCTCAGTATACATATGCCTTAAAAGAAAAAGCGAAATATCAATGCA 
               
               
                   
               
               
                 AACTAGGATATGTAACAGCAGATGGTGAAACATCAGGATCAATTACATGTGGGA 
               
               
                   
               
               
                 AAGATGGATGGTCAGCTCAACCCACGTGCATTAAATCTTGTGATATCCCAGTATT 
               
               
                   
               
               
                 TATGAATGCCAGAACTAAAAATGACTTCACATGGTTTAAGCTGAATGACACATTG 
               
               
                   
               
               
                 GACTATGAATGCCATGATGGTTATGAAAGCAATACTGGAAGCACCACTGGTTCC 
               
               
                   
               
               
                 ATAGTGTGTGGTTACAATGGTTGGTCTGATTTACCCATATGTTATGAAAGAGAAT 
               
               
                   
               
               
                 GCGAACTTCCTAAAATAGATGTACACTTAGTTCCTGATCGCAAGAAAGACCAGTA 
               
               
                   
               
               
                 TAAAGTTGGAGAGGTGTTGAAATTCTCCTGCAAACCAGGATTTACAATAGTTGGA 
               
               
                   
               
               
                 CCTAATTCCGTTCAGTGCTACCACTTTGGATTGTCTCCTGACCTCCCAATATGTAA 
               
               
                   
               
               
                 AGAGCAAGTACAATCATGTGGTCCACCTCCTGAACTCCTCAATGGGAATGTTAAG 
               
               
                   
               
               
                 GAAAAAACGAAAGAAGAATATGGACACAGTGAAGTGGTGGAATATTATTGCAAT 
               
               
                   
               
               
                 CCTAGATTTCTAATGAAGGGACCTAATAAAATTCAATGTGTTGATGGAGAGTGGA 
               
               
                   
               
               
                 CAACTTTACCAGTGTGTATTGTGGAGGAGAGTACCTGTGGAGATATACCTGAACT 
               
               
                   
               
               
                 TGAACATGGCTGGGCCCAGCTTTCTTCCCCTCCTTATTACTATGGAGATTCAGTGG 
               
               
                   
               
               
                 AATTCAATTGCTCAGAATCATTTACAATGATTGGACACAGATCAATTACGTGTAT 
               
               
                   
               
               
                 TCATGGAGTATGGACCCAACTTCCCCAGTGTGTGGCAATAGATAAACTTAAGAA 
               
               
                   
               
               
                 GTGCAAATCATCAAATTTAATTATACTTGAGGAACATTTAAAAAACAAGAAGGA 
               
               
                   
               
               
                 ATTCGATCATAATTCTAACATAAGGTACAGATGTAGAGGAAAAGAAGGATGGAT 
               
               
                   
               
               
                 ACACACAGTCTGCATAAATGGAAGATGGGATCCAGAAGTGAACTGCTCAATGGC 
               
               
                   
               
               
                 ACAAATACAATTATGCCCACCTCCACCTCAGATTCCCAATTCTCACAATATGACA 
               
               
                   
               
               
                 ACCACACTGAATTATCGGGATGGAGAAAAAGTATCTGTTCTTTGCCAAGAAAATT 
               
               
                   
               
               
                 ATCTAATTCAGGAAGGAGAAGAAATTACATGCAAAGATGGAAGATGGCAGTCAA 
               
               
                   
               
               
                 TACCACTCTGTGTTGAAAAAATTCCATGTTCACAACCACCTCAGATAGAACACGG 
               
               
                   
               
               
                 AACCATTAATTCATCCAGGTCTTCACAAGAAAGTTATGCACATGGGACTAAATTG 
               
               
                   
               
               
                 AGTTATACTTGTGAGGGTGGTTTCAGGATATCTGAAGAAAATGAAACAACATGCT 
               
               
                   
               
               
                 ACATGGGAAAATGGAGTTCTCCACCTCAGTGTGAAGGCCTTCCTTGTAAATCTCC 
               
               
                   
               
               
                 ACCTGAGATTTCTCATGGTGTTGTAGCTCACATGTCAGACAGTTATCAGTATGGA 
               
               
                   
               
               
                 GAAGAAGTTACGTACAAATGTTTTGAAGGTTTTGGAATTGATGGGCCTGCAATTG 
               
               
                   
               
               
                 CAAAATGCTTAGGAGAAAAATGGTCTCACCCTCCATCATGCATAAAAACAGATT 
               
               
                   
               
               
                 GTCTCAGTTTACCTAGCTTTGAAAATGCCATACCCATGGGAGAGAAGAAGGATGT 
               
               
                   
               
               
                 GTATAAGGCGGGTGAGCAAGTGACTTACACTTGTGCAACATATTACAAAATGGA 
               
               
                   
               
               
                 TGGAGCCAGTAATGTAACATGCATTAATAGCAGATGGACAGGAAGGCCAACATG 
               
               
                   
               
               
                 CAGAGACACCTCCTGTGTGAATCCGCCCACAGTACAAAATGCTTATATAGTGTCG 
               
               
                   
               
               
                 AGACAGATGAGTAAATATCCATCTGGTGAGAGAGTACGTTATCAATGTAGGAGC 
               
               
                   
               
               
                 CCTTATGAAATGTTTGGGGATGAAGAAGTGATGTGTTTAAATGGAAACTGGACG 
               
               
                   
               
               
                 GAACCACCTCAATGCAAAGATTCTACAGGAAAATGTGGGCCCCCTCCACCTATTG 
               
               
                   
               
               
                 ACAATGGGGACATTACTTCATTCCCGTTGTCAGTATATGCTCCAGCTTCATCAGTT 
               
               
                   
               
               
                 GAGTACCAATGCCAGAACTTGTATCAACTTGAGGGTAACAAGCGAATAACATGT 
               
               
                   
               
               
                 AGAAATGGACAATGGTCAGAACCACCAAAATGCTTACATCCGTGTGTAATATCC 
               
               
                   
               
               
                 CGAGAAATTATGGAAAATTATAACATAGCATTAAGGTGGACAGCCAAACAGAAG 
               
               
                   
               
               
                 CTTTATTCGAGAACAGGTGAATCAGTTGAATTTGTGTGTAAACGGGGATATCGTC 
               
               
                   
               
               
                 TTTCATCACGTTCTCACACATTGCGAACAACATGTTGGGATGGGAAACTGGAGTA 
               
               
                   
               
               
                 TCCAACTTGTGCAAAAAGATAGCTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTG 
               
               
                   
               
               
                 CCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCT 
               
               
                   
               
               
                 AATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGG 
               
               
                   
               
               
                 GGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGC 
               
               
                   
               
               
                 ATGCTGGGGATGCGGTGGGCTCTATGGGTTAACTCGAGGGATCCCGGACCGAGC 
               
               
                   
               
               
                 GGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTC 
               
               
                   
               
               
                 GCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGC 
               
               
                   
               
               
                 GGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTA 
               
               
                   
               
               
                 TTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATACGTCAAAGCAACCATA 
               
               
                   
               
               
                 GTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAG 
               
               
                   
               
               
                 CGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTT 
               
               
                   
               
               
                 CCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCT 
               
               
                   
               
               
                 TTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGG 
               
               
                   
               
               
                 GTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGAC 
               
               
                   
               
               
                 GTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTC 
               
               
                   
               
               
                 AACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTA 
               
               
                   
               
               
                 TTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATA 
               
               
                   
               
               
                 TTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATA 
               
               
                   
               
               
                 GTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGT 
               
               
                   
               
               
                 CTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGT 
               
               
                   
               
               
                 GTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGAGACGAAAGGGCCTCGTGA 
               
               
                   
               
               
                 TACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGT 
               
               
                   
               
               
                 GGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACA 
               
               
                   
               
               
                 TTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATAT 
               
               
                   
               
               
                 TGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTT 
               
               
                   
               
               
                 TGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAA 
               
               
                   
               
               
                 GATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAAC 
               
               
                   
               
               
                 AGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCA 
               
               
                   
               
               
                 CTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGA 
               
               
                   
               
               
                 GCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCA 
               
               
                   
               
               
                 GTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCT 
               
               
                   
               
               
                 GCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGA 
               
               
                   
               
               
                 GGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCC 
               
               
                   
               
               
                 TTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACA 
               
               
                   
               
               
                 CCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAAC 
               
               
                   
               
               
                 TACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGT 
               
               
                   
               
               
                 TGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAA 
               
               
                   
               
               
                 TCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGAT 
               
               
                   
               
               
                 GGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGG 
               
               
                   
               
               
                 ATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGT 
               
               
                   
               
               
                 AACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTT 
               
               
                   
               
               
                 TAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCC 
               
               
                   
               
               
                 CTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGG 
               
               
                   
               
               
                 ATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAAC 
               
               
                   
               
               
                 CACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCC 
               
               
                   
               
               
                 GAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAG 
               
               
                   
               
               
                 CCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTC 
               
               
                   
               
               
                 TGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGG 
               
               
                   
               
               
                 GTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGG 
               
               
                   
               
               
                 GGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATA 
               
               
                   
               
               
                 CCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGA 
               
               
                   
               
               
                 CAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCC 
               
               
                   
               
               
                 AGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTT 
               
               
                   
               
               
                 GAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCC 
               
               
                   
               
               
                 AGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 18-ALB Promoter 
               
               
                 GTTAACACGCGTTAACTAGTCAGTTCCAGATGGTAAATATACACAAGGGATTTAG 
               
               
                   
               
               
                 TCAAACAATTTTTTGGCAAGAATATTATGAATTTTGTAATCGGTTGGCAGCCAAT 
               
               
                   
               
               
                 GAAATACAAAGATGAGTCTAGTTAATAATCTACAATTATTGGTTAAAGA 
               
               
                   
               
               
                 SEQ ID NO: 19-Representative CFH AAV Vector (with ALB Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCG 
               
               
                   
               
               
                 GGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAG 
               
               
                   
               
               
                 AGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTGTTAACA 
               
               
                   
               
               
                 CGCGTTAACTAGTCAGTTCCAGATGGTAAATATACACAAGGGATTTAGTCAAACA 
               
               
                   
               
               
                 ATTTTTTGGCAAGAATATTATGAATTTTGTAATCGGTTGGCAGCCAATGAAATAC 
               
               
                   
               
               
                 AAAGATGAGTCTAGTTAATAATCTACAATTATTGGTTAAAGAATCGATAGCTGCA 
               
               
                   
               
               
                 GGCGGCCGCCGCCACCATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTATGG 
               
               
                   
               
               
                 GCTATTTGTGTAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAATACAGAA 
               
               
                   
               
               
                 ATTCTGACAGGTTCCTGGTCTGACCAAACATATCCAGAAGGCACCCAGGCTATCT 
               
               
                   
               
               
                 ATAAATGCCGCCCTGGATATAGATCTCTTGGAAATGTAATAATGGTATGCAGGAA 
               
               
                   
               
               
                 GGGAGAATGGGTTGCTCTTAATCCATTAAGGAAATGTCAGAAAAGGCCCTGTGG 
               
               
                   
               
               
                 ACATCCTGGAGATACTCCTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTG 
               
               
                   
               
               
                 AATATGGTGTAAAAGCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGA 
               
               
                   
               
               
                 GATTAATTACCGTGAATGTGACACAGATGGATGGACCAATGATATTCCTATATGT 
               
               
                   
               
               
                 GAAGTTGTGAAGTGTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGT 
               
               
                   
               
               
                 AGTGCAATGGAACCAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTA 
               
               
                   
               
               
                 TGTAACTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGAT 
               
               
                   
               
               
                 GGTTTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCCCCA 
               
               
                   
               
               
                 GATGTTATAAATGGATCTCCTATATCTCAGAAGATTATTTATAAGGAGAATGAAC 
               
               
                   
               
               
                 GATTTCAATATAAATGTAACATGGGTTATGAATACAGTGAAAGAGGAGATGCTG 
               
               
                   
               
               
                 TATGCACTGAATCTGGATGGCGTCCGTTGCCTTCATGTGAAGAAAAATCATGTGA 
               
               
                   
               
               
                 TAATCCTTATATTCCAAATGGTGACTACTCACCTTTAAGGATTAAACACAGAACT 
               
               
                   
               
               
                 GGAGATGAAATCACGTACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGA 
               
               
                   
               
               
                 AATACAGCAAAATGCACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTG 
               
               
                   
               
               
                 AAACCTTGTGATTATCCAGACATTAAACATGGAGGTCTATATCATGAGAATATGC 
               
               
                   
               
               
                 GTAGACCATACTTTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGA 
               
               
                   
               
               
                 ACATTTTGAGACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGAT 
               
               
                   
               
               
                 GGATGGTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAA 
               
               
                   
               
               
                 ATGGATATAATCAAAATTATGGAAGAAAGTTTGTACAGGGTAAATCTATAGACG 
               
               
                   
               
               
                 TTGCCTGCCATCCTGGCTACGCTCTTCCAAAAGCGCAGACCACAGTTACATGTAT 
               
               
                   
               
               
                 GGAGAATGGCTGGTCTCCTACTCCCAGATGCATCCGTGTCAAAACATGTTCCAAA 
               
               
                   
               
               
                 TCAAGTATAGATATTGAGAATGGGTTTATTTCTGAATCTCAGTATACATATGCCTT 
               
               
                   
               
               
                 AAAAGAAAAAGCGAAATATCAATGCAAACTAGGATATGTAACAGCAGATGGTG 
               
               
                   
               
               
                 AAACATCAGGATCAATTACATGTGGGAAAGATGGATGGTCAGCTCAACCCACGT 
               
               
                   
               
               
                 GCATTAAATCTTGTGATATCCCAGTATTTATGAATGCCAGAACTAAAAATGACTT 
               
               
                   
               
               
                 CACATGGTTTAAGCTGAATGACACATTGGACTATGAATGCCATGATGGTTATGAA 
               
               
                   
               
               
                 AGCAATACTGGAAGCACCACTGGTTCCATAGTGTGTGGTTACAATGGTTGGTCTG 
               
               
                   
               
               
                 ATTTACCCATATGTTATGAAAGAGAATGCGAACTTCCTAAAATAGATGTACACTT 
               
               
                   
               
               
                 AGTTCCTGATCGCAAGAAAGACCAGTATAAAGTTGGAGAGGTGTTGAAATTCTC 
               
               
                   
               
               
                 CTGCAAACCAGGATTTACAATAGTTGGACCTAATTCCGTTCAGTGCTACCACTTT 
               
               
                   
               
               
                 GGATTGTCTCCTGACCTCCCAATATGTAAAGAGCAAGTACAATCATGTGGTCCAC 
               
               
                   
               
               
                 CTCCTGAACTCCTCAATGGGAATGTTAAGGAAAAAACGAAAGAAGAATATGGAC 
               
               
                   
               
               
                 ACAGTGAAGTGGTGGAATATTATTGCAATCCTAGATTTCTAATGAAGGGACCTAA 
               
               
                   
               
               
                 TAAAATTCAATGTGTTGATGGAGAGTGGACAACTTTACCAGTGTGTATTGTGGAG 
               
               
                   
               
               
                 GAGAGTACCTGTGGAGATATACCTGAACTTGAACATGGCTGGGCCCAGCTTTCTT 
               
               
                   
               
               
                 CCCCTCCTTATTACTATGGAGATTCAGTGGAATTCAATTGCTCAGAATCATTTACA 
               
               
                   
               
               
                 ATGATTGGACACAGATCAATTACGTGTATTCATGGAGTATGGACCCAACTTCCCC 
               
               
                   
               
               
                 AGTGTGTGGCAATAGATAAACTTAAGAAGTGCAAATCATCAAATTTAATTATACT 
               
               
                   
               
               
                 TGAGGAACATTTAAAAAACAAGAAGGAATTCGATCATAATTCTAACATAAGGTA 
               
               
                   
               
               
                 CAGATGTAGAGGAAAAGAAGGATGGATACACACAGTCTGCATAAATGGAAGAT 
               
               
                   
               
               
                 GGGATCCAGAAGTGAACTGCTCAATGGCACAAATACAATTATGCCCACCTCCAC 
               
               
                   
               
               
                 CTCAGATTCCCAATTCTCACAATATGACAACCACACTGAATTATCGGGATGGAGA 
               
               
                   
               
               
                 AAAAGTATCTGTTCTTTGCCAAGAAAATTATCTAATTCAGGAAGGAGAAGAAATT 
               
               
                   
               
               
                 ACATGCAAAGATGGAAGATGGCAGTCAATACCACTCTGTGTTGAAAAAATTCCA 
               
               
                   
               
               
                 TGTTCACAACCACCTCAGATAGAACACGGAACCATTAATTCATCCAGGTCTTCAC 
               
               
                   
               
               
                 AAGAAAGTTATGCACATGGGACTAAATTGAGTTATACTTGTGAGGGTGGTTTCAG 
               
               
                   
               
               
                 GATATCTGAAGAAAATGAAACAACATGCTACATGGGAAAATGGAGTTCTCCACC 
               
               
                   
               
               
                 TCAGTGTGAAGGCCTTCCTTGTAAATCTCCACCTGAGATTTCTCATGGTGTTGTAG 
               
               
                   
               
               
                 CTCACATGTCAGACAGTTATCAGTATGGAGAAGAAGTTACGTACAAATGTTTTGA 
               
               
                   
               
               
                 AGGTTTTGGAATTGATGGGCCTGCAATTGCAAAATGCTTAGGAGAAAAATGGTCT 
               
               
                   
               
               
                 CACCCTCCATCATGCATAAAAACAGATTGTCTCAGTTTACCTAGCTTTGAAAATG 
               
               
                   
               
               
                 CCATACCCATGGGAGAGAAGAAGGATGTGTATAAGGCGGGTGAGCAAGTGACTT 
               
               
                   
               
               
                 ACACTTGTGCAACATATTACAAAATGGATGGAGCCAGTAATGTAACATGCATTA 
               
               
                   
               
               
                 ATAGCAGATGGACAGGAAGGCCAACATGCAGAGACACCTCCTGTGTGAATCCGC 
               
               
                   
               
               
                 CCACAGTACAAAATGCTTATATAGTGTCGAGACAGATGAGTAAATATCCATCTGG 
               
               
                   
               
               
                 TGAGAGAGTACGTTATCAATGTAGGAGCCCTTATGAAATGTTTGGGGATGAAGA 
               
               
                   
               
               
                 AGTGATGTGTTTAAATGGAAACTGGACGGAACCACCTCAATGCAAAGATTCTAC 
               
               
                   
               
               
                 AGGAAAATGTGGGCCCCCTCCACCTATTGACAATGGGGACATTACTTCATTCCCG 
               
               
                   
               
               
                 TTGTCAGTATATGCTCCAGCTTCATCAGTTGAGTACCAATGCCAGAACTTGTATC 
               
               
                   
               
               
                 AACTTGAGGGTAACAAGCGAATAACATGTAGAAATGGACAATGGTCAGAACCAC 
               
               
                   
               
               
                 CAAAATGCTTACATCCGTGTGTAATATCCCGAGAAATTATGGAAAATTATAACAT 
               
               
                   
               
               
                 AGCATTAAGGTGGACAGCCAAACAGAAGCTTTATTCGAGAACAGGTGAATCAGT 
               
               
                   
               
               
                 TGAATTTGTGTGTAAACGGGGATATCGTCTTTCATCACGTTCTCACACATTGCGA 
               
               
                   
               
               
                 ACAACATGTTGGGATGGGAAACTGGAGTATCCAACTTGTGCAAAAAGATAGCTG 
               
               
                   
               
               
                 TGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACC 
               
               
                   
               
               
                 CTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGC 
               
               
                   
               
               
                 ATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCA 
               
               
                   
               
               
                 AGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTA 
               
               
                   
               
               
                 TGGGTTAACTCGAGGGATCCCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGG 
               
               
                   
               
               
                 AGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAA 
               
               
                   
               
               
                 GGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCG 
               
               
                   
               
               
                 CAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGT 
               
               
                   
               
               
                 ATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATT 
               
               
                   
               
               
                 AAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGC 
               
               
                   
               
               
                 CCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTT 
               
               
                   
               
               
                 TCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTAC 
               
               
                   
               
               
                 GGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATC 
               
               
                   
               
               
                 GCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTG 
               
               
                   
               
               
                 GACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGGCTATTCTTTTGAT 
               
               
                   
               
               
                 TTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAAC 
               
               
                   
               
               
                 AAAAATTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTTTATGGTGCAC 
               
               
                   
               
               
                 TCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCA 
               
               
                   
               
               
                 ACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGAC 
               
               
                   
               
               
                 AAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACC 
               
               
                   
               
               
                 GAAACGCGCGAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTC 
               
               
                   
               
               
                 ATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCG 
               
               
                   
               
               
                 GAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGA 
               
               
                   
               
               
                 CAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATT 
               
               
                   
               
               
                 CAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTT 
               
               
                   
               
               
                 GCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCA 
               
               
                   
               
               
                 CGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTC 
               
               
                   
               
               
                 GCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGC 
               
               
                   
               
               
                 GGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTAT 
               
               
                   
               
               
                 TCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATG 
               
               
                   
               
               
                 GCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG 
               
               
                   
               
               
                 CGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTT 
               
               
                   
               
               
                 GCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAA 
               
               
                   
               
               
                 TGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAAC 
               
               
                   
               
               
                 AACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAA 
               
               
                   
               
               
                 TTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCC 
               
               
                   
               
               
                 CTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTC 
               
               
                   
               
               
                 GCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTAT 
               
               
                   
               
               
                 CTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGA 
               
               
                   
               
               
                 GATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATAT 
               
               
                   
               
               
                 ATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGA 
               
               
                   
               
               
                 TCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGA 
               
               
                   
               
               
                 GCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGC 
               
               
                   
               
               
                 GCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTT 
               
               
                   
               
               
                 GCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCG 
               
               
                   
               
               
                 CAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGA 
               
               
                   
               
               
                 ACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCT 
               
               
                   
               
               
                 GCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGG 
               
               
                   
               
               
                 ATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGG 
               
               
                   
               
               
                 AGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCG 
               
               
                   
               
               
                 CCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCG 
               
               
                   
               
               
                 GAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATA 
               
               
                   
               
               
                 GTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCA 
               
               
                   
               
               
                 GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTG 
               
               
                   
               
               
                 GCCTTTTGCTGGCCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 20-PCK1 Promoter 
               
               
                 GTTAACAGCCCCCAGTTAGGTTAGGCATTTCCAATCTTTGCCAATAAGCCACATA 
               
               
                   
               
               
                 TTTGCCCAAGTTAGGGTGCATCCTTCCCATGAACTTTGACTGTGACCTTTGACTAT 
               
               
                   
               
               
                 GGGGTGACATCTTATAGCTGTGGTGTTTTGCCAACCAGCAGCTCTTGGTACACAA 
               
               
                   
               
               
                 AATGTGCTGCTAGCAGGTGCCCCGGCCAACCTTGTCCTTGACCCACCTGCCTGTT 
               
               
                   
               
               
                 AAGAAAAGGGTGTTGTGTTTTGCAACAGCAGTAAAATGGGTCAAGGTTTAGTCA 
               
               
                   
               
               
                 GTTGGAAGTTGTGTCAAAACTCACTATGGTTGGTTGAGGGCTCGAAGTCTCCCAG 
               
               
                   
               
               
                 CATTCATTAACAACTATCTGTTCAATGATTATCTCCCTGGGGCGTGTTGCAGTGA 
               
               
                   
               
               
                 GTTGGCCCAAAGCATAACTGACCCTGGCCGTGATCCAGAGACCTGCCCCCTGACG 
               
               
                   
               
               
                 TCAGTGGCGAGCCTCCCTGGGTGCAGCTGAGGGGCAGGGCTATTCTTTTCCACAG 
               
               
                   
               
               
                 T 
               
               
                   
               
               
                 SEQ ID NO: 21-Representative CFH AAV Vector (with PCK1 Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCG 
               
               
                   
               
               
                 GGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAG 
               
               
                   
               
               
                 AGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTGTTAACA 
               
               
                   
               
               
                 GCCCCCAGTTAGGTTAGGCATTTCCAATCTTTGCCAATAAGCCACATATTTGCCC 
               
               
                   
               
               
                 AAGTTAGGGTGCATCCTTCCCATGAACTTTGACTGTGACCTTTGACTATGGGGTG 
               
               
                   
               
               
                 ACATCTTATAGCTGTGGTGTTTTGCCAACCAGCAGCTCTTGGTACACAAAATGTG 
               
               
                   
               
               
                 CTGCTAGCAGGTGCCCCGGCCAACCTTGTCCTTGACCCACCTGCCTGTTAAGAAA 
               
               
                   
               
               
                 AGGGTGTTGTGTTTTGCAACAGCAGTAAAATGGGTCAAGGTTTAGTCAGTTGGAA 
               
               
                   
               
               
                 GTTGTGTCAAAACTCACTATGGTTGGTTGAGGGCTCGAAGTCTCCCAGCATTCAT 
               
               
                   
               
               
                 TAACAACTATCTGTTCAATGATTATCTCCCTGGGGCGTGTTGCAGTGAGTTGGCC 
               
               
                   
               
               
                 CAAAGCATAACTGACCCTGGCCGTGATCCAGAGACCTGCCCCCTGACGTCAGTG 
               
               
                   
               
               
                 GCGAGCCTCCCTGGGTGCAGCTGAGGGGCAGGGCTATTCTTTTCCACAGTATCGA 
               
               
                   
               
               
                 TAGCTGCAGGCGGCCGCCGCCACCATGAGACTTCTAGCAAAGATTATTTGCCTTA 
               
               
                   
               
               
                 TGTTATGGGCTATTTGTGTAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAA 
               
               
                   
               
               
                 TACAGAAATTCTGACAGGTTCCTGGTCTGACCAAACATATCCAGAAGGCACCCA 
               
               
                   
               
               
                 GGCTATCTATAAATGCCGCCCTGGATATAGATCTCTTGGAAATGTAATAATGGTA 
               
               
                   
               
               
                 TGCAGGAAGGGAGAATGGGTTGCTCTTAATCCATTAAGGAAATGTCAGAAAAGG 
               
               
                   
               
               
                 CCCTGTGGACATCCTGGAGATACTCCTTTTGGTACTTTTACCCTTACAGGAGGAA 
               
               
                   
               
               
                 ATGTGTTTGAATATGGTGTAAAAGCTGTGTATACATGTAATGAGGGGTATCAATT 
               
               
                   
               
               
                 GCTAGGTGAGATTAATTACCGTGAATGTGACACAGATGGATGGACCAATGATAT 
               
               
                   
               
               
                 TCCTATATGTGAAGTTGTGAAGTGTTTACCAGTGACAGCACCAGAGAATGGAAA 
               
               
                   
               
               
                 AATTGTCAGTAGTGCAATGGAACCAGATCGGGAATACCATTTTGGACAAGCAGT 
               
               
                   
               
               
                 ACGGTTTGTATGTAACTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATTG 
               
               
                   
               
               
                 TTCAGACGATGGTTTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATTTCATGC 
               
               
                   
               
               
                 AAATCCCCAGATGTTATAAATGGATCTCCTATATCTCAGAAGATTATTTATAAGG 
               
               
                   
               
               
                 AGAATGAACGATTTCAATATAAATGTAACATGGGTTATGAATACAGTGAAAGAG 
               
               
                   
               
               
                 GAGATGCTGTATGCACTGAATCTGGATGGCGTCCGTTGCCTTCATGTGAAGAAAA 
               
               
                   
               
               
                 ATCATGTGATAATCCTTATATTCCAAATGGTGACTACTCACCTTTAAGGATTAAA 
               
               
                   
               
               
                 CACAGAACTGGAGATGAAATCACGTACCAGTGTAGAAATGGTTTTTATCCTGCAA 
               
               
                   
               
               
                 CCCGGGGAAATACAGCAAAATGCACAAGTACTGGCTGGATACCTGCTCCGAGAT 
               
               
                   
               
               
                 GTACCTTGAAACCTTGTGATTATCCAGACATTAAACATGGAGGTCTATATCATGA 
               
               
                   
               
               
                 GAATATGCGTAGACCATACTTTCCAGTAGCTGTAGGAAAATATTACTCCTATTAC 
               
               
                   
               
               
                 TGTGATGAACATTTTGAGACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCA 
               
               
                   
               
               
                 CACAAGATGGATGGTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTCCTTA 
               
               
                   
               
               
                 TTTGGAAAATGGATATAATCAAAATTATGGAAGAAAGTTTGTACAGGGTAAATC 
               
               
                   
               
               
                 TATAGACGTTGCCTGCCATCCTGGCTACGCTCTTCCAAAAGCGCAGACCACAGTT 
               
               
                   
               
               
                 ACATGTATGGAGAATGGCTGGTCTCCTACTCCCAGATGCATCCGTGTCAAAACAT 
               
               
                   
               
               
                 GTTCCAAATCAAGTATAGATATTGAGAATGGGTTTATTTCTGAATCTCAGTATAC 
               
               
                   
               
               
                 ATATGCCTTAAAAGAAAAAGCGAAATATCAATGCAAACTAGGATATGTAACAGC 
               
               
                   
               
               
                 AGATGGTGAAACATCAGGATCAATTACATGTGGGAAAGATGGATGGTCAGCTCA 
               
               
                   
               
               
                 ACCCACGTGCATTAAATCTTGTGATATCCCAGTATTTATGAATGCCAGAACTAAA 
               
               
                   
               
               
                 AATGACTTCACATGGTTTAAGCTGAATGACACATTGGACTATGAATGCCATGATG 
               
               
                   
               
               
                 GTTATGAAAGCAATACTGGAAGCACCACTGGTTCCATAGTGTGTGGTTACAATGG 
               
               
                   
               
               
                 TTGGTCTGATTTACCCATATGTTATGAAAGAGAATGCGAACTTCCTAAAATAGAT 
               
               
                   
               
               
                 GTACACTTAGTTCCTGATCGCAAGAAAGACCAGTATAAAGTTGGAGAGGTGTTG 
               
               
                   
               
               
                 AAATTCTCCTGCAAACCAGGATTTACAATAGTTGGACCTAATTCCGTTCAGTGCT 
               
               
                   
               
               
                 ACCACTTTGGATTGTCTCCTGACCTCCCAATATGTAAAGAGCAAGTACAATCATG 
               
               
                   
               
               
                 TGGTCCACCTCCTGAACTCCTCAATGGGAATGTTAAGGAAAAAACGAAAGAAGA 
               
               
                   
               
               
                 ATATGGACACAGTGAAGTGGTGGAATATTATTGCAATCCTAGATTTCTAATGAAG 
               
               
                   
               
               
                 GGACCTAATAAAATTCAATGTGTTGATGGAGAGTGGACAACTTTACCAGTGTGTA 
               
               
                   
               
               
                 TTGTGGAGGAGAGTACCTGTGGAGATATACCTGAACTTGAACATGGCTGGGCCC 
               
               
                   
               
               
                 AGCTTTCTTCCCCTCCTTATTACTATGGAGATTCAGTGGAATTCAATTGCTCAGAA 
               
               
                   
               
               
                 TCATTTACAATGATTGGACACAGATCAATTACGTGTATTCATGGAGTATGGACCC 
               
               
                   
               
               
                 AACTTCCCCAGTGTGTGGCAATAGATAAACTTAAGAAGTGCAAATCATCAAATTT 
               
               
                   
               
               
                 AATTATACTTGAGGAACATTTAAAAAACAAGAAGGAATTCGATCATAATTCTAA 
               
               
                   
               
               
                 CATAAGGTACAGATGTAGAGGAAAAGAAGGATGGATACACACAGTCTGCATAAA 
               
               
                   
               
               
                 TGGAAGATGGGATCCAGAAGTGAACTGCTCAATGGCACAAATACAATTATGCCC 
               
               
                   
               
               
                 ACCTCCACCTCAGATTCCCAATTCTCACAATATGACAACCACACTGAATTATCGG 
               
               
                   
               
               
                 GATGGAGAAAAAGTATCTGTTCTTTGCCAAGAAAATTATCTAATTCAGGAAGGA 
               
               
                   
               
               
                 GAAGAAATTACATGCAAAGATGGAAGATGGCAGTCAATACCACTCTGTGTTGAA 
               
               
                   
               
               
                 AAAATTCCATGTTCACAACCACCTCAGATAGAACACGGAACCATTAATTCATCCA 
               
               
                   
               
               
                 GGTCTTCACAAGAAAGTTATGCACATGGGACTAAATTGAGTTATACTTGTGAGGG 
               
               
                   
               
               
                 TGGTTTCAGGATATCTGAAGAAAATGAAACAACATGCTACATGGGAAAATGGAG 
               
               
                   
               
               
                 TTCTCCACCTCAGTGTGAAGGCCTTCCTTGTAAATCTCCACCTGAGATTTCTCATG 
               
               
                   
               
               
                 GTGTTGTAGCTCACATGTCAGACAGTTATCAGTATGGAGAAGAAGTTACGTACAA 
               
               
                   
               
               
                 ATGTTTTGAAGGTTTTGGAATTGATGGGCCTGCAATTGCAAAATGCTTAGGAGAA 
               
               
                   
               
               
                 AAATGGTCTCACCCTCCATCATGCATAAAAACAGATTGTCTCAGTTTACCTAGCT 
               
               
                   
               
               
                 TTGAAAATGCCATACCCATGGGAGAGAAGAAGGATGTGTATAAGGCGGGTGAGC 
               
               
                   
               
               
                 AAGTGACTTACACTTGTGCAACATATTACAAAATGGATGGAGCCAGTAATGTAA 
               
               
                   
               
               
                 CATGCATTAATAGCAGATGGACAGGAAGGCCAACATGCAGAGACACCTCCTGTG 
               
               
                   
               
               
                 TGAATCCGCCCACAGTACAAAATGCTTATATAGTGTCGAGACAGATGAGTAAAT 
               
               
                   
               
               
                 ATCCATCTGGTGAGAGAGTACGTTATCAATGTAGGAGCCCTTATGAAATGTTTGG 
               
               
                   
               
               
                 GGATGAAGAAGTGATGTGTTTAAATGGAAACTGGACGGAACCACCTCAATGCAA 
               
               
                   
               
               
                 AGATTCTACAGGAAAATGTGGGCCCCCTCCACCTATTGACAATGGGGACATTACT 
               
               
                   
               
               
                 TCATTCCCGTTGTCAGTATATGCTCCAGCTTCATCAGTTGAGTACCAATGCCAGA 
               
               
                   
               
               
                 ACTTGTATCAACTTGAGGGTAACAAGCGAATAACATGTAGAAATGGACAATGGT 
               
               
                   
               
               
                 CAGAACCACCAAAATGCTTACATCCGTGTGTAATATCCCGAGAAATTATGGAAA 
               
               
                   
               
               
                 ATTATAACATAGCATTAAGGTGGACAGCCAAACAGAAGCTTTATTCGAGAACAG 
               
               
                   
               
               
                 GTGAATCAGTTGAATTTGTGTGTAAACGGGGATATCGTCTTTCATCACGTTCTCA 
               
               
                   
               
               
                 CACATTGCGAACAACATGTTGGGATGGGAAACTGGAGTATCCAACTTGTGCAAA 
               
               
                   
               
               
                 AAGATAGCTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCC 
               
               
                   
               
               
                 TTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAA 
               
               
                   
               
               
                 ATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGC 
               
               
                   
               
               
                 AGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCG 
               
               
                   
               
               
                 GTGGGCTCTATGGGTTAACTCGAGGGATCCCGGACCGAGCGGCCGCAGGAACCC 
               
               
                   
               
               
                 CTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCG 
               
               
                   
               
               
                 GGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCG 
               
               
                   
               
               
                 AGCGAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCA 
               
               
                   
               
               
                 TCTGTGCGGTATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTA 
               
               
                   
               
               
                 GCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACAC 
               
               
                   
               
               
                 TTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGT 
               
               
                   
               
               
                 TCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTT 
               
               
                   
               
               
                 AGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTTCACGTA 
               
               
                   
               
               
                 GTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTT 
               
               
                   
               
               
                 CTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGGC 
               
               
                   
               
               
                 TATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGA 
               
               
                   
               
               
                 GCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGTTTACAATT 
               
               
                   
               
               
                 TTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCC 
               
               
                   
               
               
                 GACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATC 
               
               
                   
               
               
                 CGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCA 
               
               
                   
               
               
                 CCGTCATCACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACGCCTATTTTTAT 
               
               
                   
               
               
                 AGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGG 
               
               
                   
               
               
                 AAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATC 
               
               
                   
               
               
                 CGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGA 
               
               
                   
               
               
                 GTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGC 
               
               
                   
               
               
                 CTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATC 
               
               
                   
               
               
                 AGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCC 
               
               
                   
               
               
                 TTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCT 
               
               
                   
               
               
                 GCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGC 
               
               
                   
               
               
                 CGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGC 
               
               
                   
               
               
                 ATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGA 
               
               
                   
               
               
                 GTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGC 
               
               
                   
               
               
                 TAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGA 
               
               
                   
               
               
                 ACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGT 
               
               
                   
               
               
                 AGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCT 
               
               
                   
               
               
                 TCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTT 
               
               
                   
               
               
                 CTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTG 
               
               
                   
               
               
                 AGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG 
               
               
                   
               
               
                 TATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAG 
               
               
                   
               
               
                 ACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAA 
               
               
                   
               
               
                 GTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGAT 
               
               
                   
               
               
                 CTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTT 
               
               
                   
               
               
                 CGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCC 
               
               
                   
               
               
                 TTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCG 
               
               
                   
               
               
                 GTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCT 
               
               
                   
               
               
                 TCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCA 
               
               
                   
               
               
                 CCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTAC 
               
               
                   
               
               
                 CAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACG 
               
               
                   
               
               
                 ATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACA 
               
               
                   
               
               
                 GCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCT 
               
               
                   
               
               
                 ATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAA 
               
               
                   
               
               
                 GCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCC 
               
               
                   
               
               
                 TGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTT 
               
               
                   
               
               
                 GTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTT 
               
               
                   
               
               
                 TTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 22-Representative FHL AAV Vector (with EF1a Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAG 
               
               
                   
               
               
                 CCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGC 
               
               
                   
               
               
                 GCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGGG 
               
               
                   
               
               
                 GCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGG 
               
               
                   
               
               
                 CAATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTG 
               
               
                   
               
               
                 ATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGAACCGTAT 
               
               
                   
               
               
                 ATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGC 
               
               
                   
               
               
                 CAGAACACAGACCGGTCTCGAAGGCCTGCAGGCGGCCGCCGCCACCATGA 
               
               
                   
               
               
                 ATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTATGGGCTATTTGTGT 
               
               
                   
               
               
                 AGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAATACAGAAATTCTGA 
               
               
                   
               
               
                 CAGGTTCCTGGTCTGACCAAACATATCCAGAAGGCACCCAGGCTATCTAT 
               
               
                   
               
               
                 AAATGCCGCCCTGGATATAGATCTCTTGGAAATGTAATAATGGTATGCAG 
               
               
                   
               
               
                 GAAGGGAGAATGGGTTGCTCTTAATCCATTAAGGAAATGTCAGAAAAGGC 
               
               
                   
               
               
                 CCTGTGGACATCCTGGAGATACTCCTTTTGGTACTTTTACCCTTACAGGA 
               
               
                   
               
               
                 GGAAATGTGTTTGAATATGGTGTAAAAGCTGTGTATACATGTAATGAGGG 
               
               
                   
               
               
                 GTATCAATTGCTAGGTGAGATTAATTACCGTGAATGTGACACAGATGGAT 
               
               
                   
               
               
                 GGACCAATGATATTCCTATATGTGAAGTTGTGAAGTGTTTACCAGTGACA 
               
               
                   
               
               
                 GCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATGGAACCAGATCGGGA 
               
               
                   
               
               
                 ATACCATTTTGGACAAGCAGTACGGTTTGTATGTAACTCAGGCTACAAGA 
               
               
                   
               
               
                 TTGAAGGAGATGAAGAAATGCATTGTTCAGACGATGGTTTTTGGAGTAAA 
               
               
                   
               
               
                 GAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCCCCAGATGTTATAAA 
               
               
                   
               
               
                 TGGATCTCCTATATCTCAGAAGATTATTTATAAGGAGAATGAACGATTTC 
               
               
                   
               
               
                 AATATAAATGTAACATGGGTTATGAATACAGTGAAAGAGGAGATGCTGTA 
               
               
                   
               
               
                 TGCACTGAATCTGGATGGCGTCCGTTGCCTTCATGTGAAGAAAAATCATG 
               
               
                   
               
               
                 TGATAATCCTTATATTCCAAATGGTGACTACTCACCTTTAAGGATTAAAC 
               
               
                   
               
               
                 ACAGAACTGGAGATGAAATCACGTACCAGTGTAGAAATGGTTTTTATCCT 
               
               
                   
               
               
                 GCAACCCGGGGAAATACAGCAAAATGCACAAGTACTGGCTGGATACCTGC 
               
               
                   
               
               
                 TCCGAGATGTACCTTGAAACCTTGTGATTATCCAGACATTAAACATGGAG 
               
               
                   
               
               
                 GTCTATATCATGAGAATATGCGTAGACCATACTTTCCAGTAGCTGTAGGA 
               
               
                   
               
               
                 AAATATTACTCCTATTACTGTGATGAACATTTTGAGACTCCGTCAGGAAG 
               
               
                   
               
               
                 TTACTGGGATCACATTCATTGCACACAAGATGGATGGTCGCCAGCAGTAC 
               
               
                   
               
               
                 CATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAAATGGATATAATCAA 
               
               
                   
               
               
                 AATCATGGAAGAAAGTTTGTACAGGGTAAATCTATAGACGTTGCCTGCCA 
               
               
                   
               
               
                 TCCTGGCTACGCTCTTCCAAAAGCGCAGACCACAGTTACATGTATGGAGA 
               
               
                   
               
               
                 ATGGCTGGTCTCCTACTCCCAGATGCATCCGTGTCAGCTTTACCCTCTGA 
               
               
                   
               
               
                 TAAGATATCGATACATTGATGAGTTTGGACAAACCACAACTAGAATGCAG 
               
               
                   
               
               
                 TGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCTATTGCTTTATTTGT 
               
               
                   
               
               
                 AACCATTATAAGCTGCAATAAACAAGATATCGTTAACTCGAGGGATCCCA 
               
               
                   
               
               
                 CGTGCTGATTTTGTAGGTAACCACGTGCGGACCGAGCGGCCGCAGGAACC 
               
               
                   
               
               
                 CCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTG 
               
               
                   
               
               
                 AGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC 
               
               
                   
               
               
                 TCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTA 
               
               
                   
               
               
                 TTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATACGTCAAAGCA 
               
               
                   
               
               
                 ACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGG 
               
               
                   
               
               
                 TTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCT 
               
               
                   
               
               
                 TTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCA 
               
               
                   
               
               
                 AGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGC 
               
               
                   
               
               
                 ACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCA 
               
               
                   
               
               
                 TCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTT 
               
               
                   
               
               
                 TAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGG 
               
               
                   
               
               
                 GCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTA 
               
               
                   
               
               
                 AAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATT 
               
               
                   
               
               
                 AACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCG 
               
               
                   
               
               
                 CATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGA 
               
               
                   
               
               
                 CGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTC 
               
               
                   
               
               
                 CGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGA 
               
               
                   
               
               
                 GACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATA 
               
               
                   
               
               
                 ATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGG 
               
               
                   
               
               
                 AACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCA 
               
               
                   
               
               
                 TGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGT 
               
               
                   
               
               
                 ATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATT 
               
               
                   
               
               
                 TTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATG 
               
               
                   
               
               
                 CTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAAC 
               
               
                   
               
               
                 AGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGAT 
               
               
                   
               
               
                 GAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACG 
               
               
                   
               
               
                 CCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTG 
               
               
                   
               
               
                 GTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGT 
               
               
                   
               
               
                 AAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCA 
               
               
                   
               
               
                 ACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTG 
               
               
                   
               
               
                 CACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCT 
               
               
                   
               
               
                 GAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAA 
               
               
                   
               
               
                 TGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCT 
               
               
                   
               
               
                 TCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACC 
               
               
                   
               
               
                 ACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTG 
               
               
                   
               
               
                 GAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGAT 
               
               
                   
               
               
                 GGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAAC 
               
               
                   
               
               
                 TATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTA 
               
               
                   
               
               
                 AGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGAT 
               
               
                   
               
               
                 TTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGA 
               
               
                   
               
               
                 TAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGT 
               
               
                   
               
               
                 CAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTG 
               
               
                   
               
               
                 CGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGT 
               
               
                   
               
               
                 TTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCT 
               
               
                   
               
               
                 TCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTA 
               
               
                   
               
               
                 GGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCT 
               
               
                   
               
               
                 AATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCG 
               
               
                   
               
               
                 GGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGA 
               
               
                   
               
               
                 ACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGA 
               
               
                   
               
               
                 ACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAG 
               
               
                   
               
               
                 GGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAG 
               
               
                   
               
               
                 CGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGT 
               
               
                   
               
               
                 CGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAG 
               
               
                   
               
               
                 GGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTC 
               
               
                   
               
               
                 CTGGCCTTTTGCTGGCCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 23-Representative FHL AAV Vector (with ALB Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAG 
               
               
                   
               
               
                 CCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGC 
               
               
                   
               
               
                 GCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCA 
               
               
                   
               
               
                 GTTCCAGATGGTAAATATACACAAGGGATTTAGTCAAACAATTTTTTGGC 
               
               
                   
               
               
                 AAGAATATTATGAATTTTGTAATCGGTTGGCAGCCAATGAAATACAAAGA 
               
               
                   
               
               
                 TGAGTCTAGTTAATAATCTACAATTATTGGTTAAAGACCGGTCTCGAAGG 
               
               
                   
               
               
                 CCTGCAGGCGGCCGCCGCCACCATGAATGAGACTTCTAGCAAAGATTATT 
               
               
                   
               
               
                 TGCCTTATGTTATGGGCTATTTGTGTAGCAGAAGATTGCAATGAACTTCC 
               
               
                   
               
               
                 TCCAAGAAGAAATACAGAAATTCTGACAGGTTCCTGGTCTGACCAAACAT 
               
               
                   
               
               
                 ATCCAGAAGGCACCCAGGCTATCTATAAATGCCGCCCTGGATATAGATCT 
               
               
                   
               
               
                 CTTGGAAATGTAATAATGGTATGCAGGAAGGGAGAATGGGTTGCTCTTAA 
               
               
                   
               
               
                 TCCATTAAGGAAATGTCAGAAAAGGCCCTGTGGACATCCTGGAGATACTC 
               
               
                   
               
               
                 CTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGTA 
               
               
                   
               
               
                 AAAGCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAA 
               
               
                   
               
               
                 TTACCGTGAATGTGACACAGATGGATGGACCAATGATATTCCTATATGTG 
               
               
                   
               
               
                 AAGTTGTGAAGTGTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTC 
               
               
                   
               
               
                 AGTAGTGCAATGGAACCAGATCGGGAATACCATTTTGGACAAGCAGTACG 
               
               
                   
               
               
                 GTTTGTATGTAACTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATT 
               
               
                   
               
               
                 GTTCAGACGATGGTTTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATT 
               
               
                   
               
               
                 TCATGCAAATCCCCAGATGTTATAAATGGATCTCCTATATCTCAGAAGAT 
               
               
                   
               
               
                 TATTTATAAGGAGAATGAACGATTTCAATATAAATGTAACATGGGTTATG 
               
               
                   
               
               
                 AATACAGTGAAAGAGGAGATGCTGTATGCACTGAATCTGGATGGCGTCCG 
               
               
                   
               
               
                 TTGCCTTCATGTGAAGAAAAATCATGTGATAATCCTTATATTCCAAATGG 
               
               
                   
               
               
                 TGACTACTCACCTTTAAGGATTAAACACAGAACTGGAGATGAAATCACGT 
               
               
                   
               
               
                 ACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAAA 
               
               
                   
               
               
                 TGCACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTG 
               
               
                   
               
               
                 TGATTATCCAGACATTAAACATGGAGGTCTATATCATGAGAATATGCGTA 
               
               
                   
               
               
                 GACCATACTTTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGAT 
               
               
                   
               
               
                 GAACATTTTGAGACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCAC 
               
               
                   
               
               
                 ACAAGATGGATGGTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTC 
               
               
                   
               
               
                 CTTATTTGGAAAATGGATATAATCAAAATCATGGAAGAAAGTTTGTACAG 
               
               
                   
               
               
                 GGTAAATCTATAGACGTTGCCTGCCATCCTGGCTACGCTCTTCCAAAAGC 
               
               
                   
               
               
                 GCAGACCACAGTTACATGTATGGAGAATGGCTGGTCTCCTACTCCCAGAT 
               
               
                   
               
               
                 GCATCCGTGTCAGCTTTACCCTCTGATAAGATATCGATACATTGATGAGT 
               
               
                   
               
               
                 TTGGACAAACCACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAA 
               
               
                   
               
               
                 ATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACA 
               
               
                   
               
               
                 AGATATCGTTAACTCGAGGGATCCCACGTGCTGATTTTGTAGGTAACCAC 
               
               
                   
               
               
                 GTGCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCC 
               
               
                   
               
               
                 CTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCC 
               
               
                   
               
               
                 GACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGC 
               
               
                   
               
               
                 TGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGG 
               
               
                   
               
               
                 TATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGG 
               
               
                   
               
               
                 CGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACAC 
               
               
                   
               
               
                 TTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTC 
               
               
                   
               
               
                 GCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTT 
               
               
                   
               
               
                 AGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATT 
               
               
                   
               
               
                 TGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGC 
               
               
                   
               
               
                 CCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAAC 
               
               
                   
               
               
                 TGGAACAACACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGA 
               
               
                   
               
               
                 TTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAA 
               
               
                   
               
               
                 TTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTTTATGGTGCAC 
               
               
                   
               
               
                 TCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACC 
               
               
                   
               
               
                 CGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCC 
               
               
                   
               
               
                 GCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTT 
               
               
                   
               
               
                 TTCACCGTCATCACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACGCC 
               
               
                   
               
               
                 TATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGT 
               
               
                   
               
               
                 GGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTA 
               
               
                   
               
               
                 AATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGC 
               
               
                   
               
               
                 TTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTC 
               
               
                   
               
               
                 GCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCC 
               
               
                   
               
               
                 AGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAG 
               
               
                   
               
               
                 TGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTT 
               
               
                   
               
               
                 CGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATG 
               
               
                   
               
               
                 TGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCC 
               
               
                   
               
               
                 GCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAA 
               
               
                   
               
               
                 AAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCAT 
               
               
                   
               
               
                 AACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAG 
               
               
                   
               
               
                 GACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACT 
               
               
                   
               
               
                 CGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGA 
               
               
                   
               
               
                 GCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTAT 
               
               
                   
               
               
                 TAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGG 
               
               
                   
               
               
                 ATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGC 
               
               
                   
               
               
                 TGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCG 
               
               
                   
               
               
                 GTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTT 
               
               
                   
               
               
                 ATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGAT 
               
               
                   
               
               
                 CGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAG 
               
               
                   
               
               
                 TTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAA 
               
               
                   
               
               
                 AGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTA 
               
               
                   
               
               
                 ACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAG 
               
               
                   
               
               
                 GATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACA 
               
               
                   
               
               
                 AAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACC 
               
               
                   
               
               
                 AACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATA 
               
               
                   
               
               
                 CTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTA 
               
               
                   
               
               
                 GCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGC 
               
               
                   
               
               
                 CAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTAC 
               
               
                   
               
               
                 CGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCC 
               
               
                   
               
               
                 AGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCT 
               
               
                   
               
               
                 ATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGG 
               
               
                   
               
               
                 TAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGA 
               
               
                   
               
               
                 AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGA 
               
               
                   
               
               
                 GCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACG 
               
               
                   
               
               
                 CCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCT 
               
               
                   
               
               
                 CACATGT 
               
               
                   
               
               
                 SEQ ID NO: 24-Representative FHL AAV Vector (with AAT1 Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAG 
               
               
                   
               
               
                 CCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGC 
               
               
                   
               
               
                 GCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCA 
               
               
                   
               
               
                 GTTCCAGATGGTAAATATACACAAGGGATTTAGTCAAACAATTTTTTGGC 
               
               
                   
               
               
                 AAGAATATTATGAATTTTGTAATCGGTTGGCAGCCAATGAAATACAAAGA 
               
               
                   
               
               
                 TGAGTCTAGTTAATAATCTACAATTATTGGTTAAAGACCGGTCTCGAAGG 
               
               
                   
               
               
                 CCTGCAGGCGGCCGCCGCCACCATGAATGAGACTTCTAGCAAAGATTATT 
               
               
                   
               
               
                 TGCCTTATGTTATGGGCTATTTGTGTAGCAGAAGATTGCAATGAACTTCC 
               
               
                   
               
               
                 TCCAAGAAGAAATACAGAAATTCTGACAGGTTCCTGGTCTGACCAAACAT 
               
               
                   
               
               
                 ATCCAGAAGGCACCCAGGCTATCTATAAATGCCGCCCTGGATATAGATCT 
               
               
                   
               
               
                 CTTGGAAATGTAATAATGGTATGCAGGAAGGGAGAATGGGTTGCTCTTAA 
               
               
                   
               
               
                 TCCATTAAGGAAATGTCAGAAAAGGCCCTGTGGACATCCTGGAGATACTC 
               
               
                   
               
               
                 CTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGTA 
               
               
                   
               
               
                 AAAGCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAA 
               
               
                   
               
               
                 TTACCGTGAATGTGACACAGATGGATGGACCAATGATATTCCTATATGTG 
               
               
                   
               
               
                 AAGTTGTGAAGTGTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTC 
               
               
                   
               
               
                 AGTAGTGCAATGGAACCAGATCGGGAATACCATTTTGGACAAGCAGTACG 
               
               
                   
               
               
                 GTTTGTATGTAACTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATT 
               
               
                   
               
               
                 GTTCAGACGATGGTTTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATT 
               
               
                   
               
               
                 TCATGCAAATCCCCAGATGTTATAAATGGATCTCCTATATCTCAGAAGAT 
               
               
                   
               
               
                 TATTTATAAGGAGAATGAACGATTTCAATATAAATGTAACATGGGTTATG 
               
               
                   
               
               
                 AATACAGTGAAAGAGGAGATGCTGTATGCACTGAATCTGGATGGCGTCCG 
               
               
                   
               
               
                 TTGCCTTCATGTGAAGAAAAATCATGTGATAATCCTTATATTCCAAATGG 
               
               
                   
               
               
                 TGACTACTCACCTTTAAGGATTAAACACAGAACTGGAGATGAAATCACGT 
               
               
                   
               
               
                 ACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAAA 
               
               
                   
               
               
                 TGCACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTG 
               
               
                   
               
               
                 TGATTATCCAGACATTAAACATGGAGGTCTATATCATGAGAATATGCGTA 
               
               
                   
               
               
                 GACCATACTTTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGAT 
               
               
                   
               
               
                 GAACATTTTGAGACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCAC 
               
               
                   
               
               
                 ACAAGATGGATGGTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTC 
               
               
                   
               
               
                 CTTATTTGGAAAATGGATATAATCAAAATCATGGAAGAAAGTTTGTACAG 
               
               
                   
               
               
                 GGTAAATCTATAGACGTTGCCTGCCATCCTGGCTACGCTCTTCCAAAAGC 
               
               
                   
               
               
                 GCAGACCACAGTTACATGTATGGAGAATGGCTGGTCTCCTACTCCCAGAT 
               
               
                   
               
               
                 GCATCCGTGTCAGCTTTACCCTCTGATAAGATATCGATACATTGATGAGT 
               
               
                   
               
               
                 TTGGACAAACCACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAA 
               
               
                   
               
               
                 ATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACA 
               
               
                   
               
               
                 AGATATCGTTAACTCGAGGGATCCCACGTGCTGATTTTGTAGGTAACCAC 
               
               
                   
               
               
                 GTGCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCC 
               
               
                   
               
               
                 CTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCC 
               
               
                   
               
               
                 GACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGC 
               
               
                   
               
               
                 TGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGG 
               
               
                   
               
               
                 TATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGG 
               
               
                   
               
               
                 CGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACAC 
               
               
                   
               
               
                 TTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTC 
               
               
                   
               
               
                 GCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTT 
               
               
                   
               
               
                 AGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATT 
               
               
                   
               
               
                 TGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGC 
               
               
                   
               
               
                 CCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAAC 
               
               
                   
               
               
                 TGGAACAACACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGA 
               
               
                   
               
               
                 TTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAA 
               
               
                   
               
               
                 TTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTTTATGGTGCAC 
               
               
                   
               
               
                 TCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACC 
               
               
                   
               
               
                 CGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCC 
               
               
                   
               
               
                 GCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTT 
               
               
                   
               
               
                 TTCACCGTCATCACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACGCC 
               
               
                   
               
               
                 TATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGT 
               
               
                   
               
               
                 GGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTA 
               
               
                   
               
               
                 AATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGC 
               
               
                   
               
               
                 TTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTC 
               
               
                   
               
               
                 GCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCC 
               
               
                   
               
               
                 AGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAG 
               
               
                   
               
               
                 TGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTT 
               
               
                   
               
               
                 CGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATG 
               
               
                   
               
               
                 TGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCC 
               
               
                   
               
               
                 GCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAA 
               
               
                   
               
               
                 AAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCAT 
               
               
                   
               
               
                 AACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAG 
               
               
                   
               
               
                 GACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACT 
               
               
                   
               
               
                 CGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGA 
               
               
                   
               
               
                 GCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTAT 
               
               
                   
               
               
                 TAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGG 
               
               
                   
               
               
                 ATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGC 
               
               
                   
               
               
                 TGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCG 
               
               
                   
               
               
                 GTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTT 
               
               
                   
               
               
                 ATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGAT 
               
               
                   
               
               
                 CGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAG 
               
               
                   
               
               
                 TTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAA 
               
               
                   
               
               
                 AGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTA 
               
               
                   
               
               
                 ACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAG 
               
               
                   
               
               
                 GATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACA 
               
               
                   
               
               
                 AAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACC 
               
               
                   
               
               
                 AACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATA 
               
               
                   
               
               
                 CTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTA 
               
               
                   
               
               
                 GCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGC 
               
               
                   
               
               
                 CAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTAC 
               
               
                   
               
               
                 CGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCC 
               
               
                   
               
               
                 AGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCT 
               
               
                   
               
               
                 ATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGG 
               
               
                   
               
               
                 TAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGA 
               
               
                   
               
               
                 AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGA 
               
               
                   
               
               
                 GCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACG 
               
               
                   
               
               
                 CCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCT 
               
               
                   
               
               
                 CACATGT 
               
               
                   
               
               
                 SEQ ID NO: 25-Representative FHL AAV Vector (with EF1a.SV40i  
               
               
                 Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAG 
               
               
                   
               
               
                 CCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGC 
               
               
                   
               
               
                 GCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGAC 
               
               
                   
               
               
                 GCGTTAACTAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTG 
               
               
                   
               
               
                 GGGGGAGGGGTCGGCAATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGGT 
               
               
                   
               
               
                 AAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTG 
               
               
                   
               
               
                 GGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGC 
               
               
                   
               
               
                 AACGGGTTTGCCGCCAGAACACAGGTAAGTTTAGTCTTTTTGTCTTTTAT 
               
               
                   
               
               
                 TTCAGGTCCCGGATCCGGTGGTGGTGCAAATCAAAGAACTGCTCCTCAGT 
               
               
                   
               
               
                 GGATGTTGCCTTTACTTCTAGGCCTGTACGGAAGTGTTACTTCTGCTCTA 
               
               
                   
               
               
                 AAAGCTGCGGAATTGTACCCGCGGACCGGTCTCGAAGGCCTGCAGGCGGC 
               
               
                   
               
               
                 CGCCGCCACCATGAATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTA 
               
               
                   
               
               
                 TGGGCTATTTGTGTAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAA 
               
               
                   
               
               
                 TACAGAAATTCTGACAGGTTCCTGGTCTGACCAAACATATCCAGAAGGCA 
               
               
                   
               
               
                 CCCAGGCTATCTATAAATGCCGCCCTGGATATAGATCTCTTGGAAATGTA 
               
               
                   
               
               
                 ATAATGGTATGCAGGAAGGGAGAATGGGTTGCTCTTAATCCATTAAGGAA 
               
               
                   
               
               
                 ATGTCAGAAAAGGCCCTGTGGACATCCTGGAGATACTCCTTTTGGTACTT 
               
               
                   
               
               
                 TTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGTAAAAGCTGTGTAT 
               
               
                   
               
               
                 ACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTACCGTGAATG 
               
               
                   
               
               
                 TGACACAGATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGAAGT 
               
               
                   
               
               
                 GTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATG 
               
               
                   
               
               
                 GAACCAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGTAA 
               
               
                   
               
               
                 CTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATG 
               
               
                   
               
               
                 GTTTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCC 
               
               
                   
               
               
                 CCAGATGTTATAAATGGATCTCCTATATCTCAGAAGATTATTTATAAGGA 
               
               
                   
               
               
                 GAATGAACGATTTCAATATAAATGTAACATGGGTTATGAATACAGTGAAA 
               
               
                   
               
               
                 GAGGAGATGCTGTATGCACTGAATCTGGATGGCGTCCGTTGCCTTCATGT 
               
               
                   
               
               
                 GAAGAAAAATCATGTGATAATCCTTATATTCCAAATGGTGACTACTCACC 
               
               
                   
               
               
                 TTTAAGGATTAAACACAGAACTGGAGATGAAATCACGTACCAGTGTAGAA 
               
               
                   
               
               
                 ATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAAATGCACAAGTACT 
               
               
                   
               
               
                 GGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGATTATCCAGA 
               
               
                   
               
               
                 CATTAAACATGGAGGTCTATATCATGAGAATATGCGTAGACCATACTTTC 
               
               
                   
               
               
                 CAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACATTTTGAG 
               
               
                   
               
               
                 ACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGATG 
               
               
                   
               
               
                 GTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAA 
               
               
                   
               
               
                 ATGGATATAATCAAAATCATGGAAGAAAGTTTGTACAGGGTAAATCTATA 
               
               
                   
               
               
                 GACGTTGCCTGCCATCCTGGCTACGCTCTTCCAAAAGCGCAGACCACAGT 
               
               
                   
               
               
                 TACATGTATGGAGAATGGCTGGTCTCCTACTCCCAGATGCATCCGTGTCA 
               
               
                   
               
               
                 GCTTTACCCTCTGATAAGATATCGATACATTGATGAGTTTGGACAAACCA 
               
               
                   
               
               
                 CAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCT 
               
               
                   
               
               
                 ATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACAAGATATCGTTAA 
               
               
                   
               
               
                 CTCGAGGGATCCCACGTGCTGATTTTGTAGGTAACCACGTGCGGACCGAG 
               
               
                   
               
               
                 CGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGC 
               
               
                   
               
               
                 TCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCT 
               
               
                   
               
               
                 TTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGG 
               
               
                   
               
               
                 CGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCG 
               
               
                   
               
               
                 CATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGC 
               
               
                   
               
               
                 GGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCC 
               
               
                   
               
               
                 TAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCC 
               
               
                   
               
               
                 GGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATT 
               
               
                   
               
               
                 TAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTT 
               
               
                   
               
               
                 CACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTG 
               
               
                   
               
               
                 GAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACT 
               
               
                   
               
               
                 CAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGATTT 
               
               
                   
               
               
                 CGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAAT 
               
               
                   
               
               
                 TTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAAT 
               
               
                   
               
               
                 CTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCG 
               
               
                   
               
               
                 CTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAA 
               
               
                   
               
               
                 GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATC 
               
               
                   
               
               
                 ACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGG 
               
               
                   
               
               
                 TTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGG 
               
               
                   
               
               
                 GGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAA 
               
               
                   
               
               
                 TATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATT 
               
               
                   
               
               
                 GAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCC 
               
               
                   
               
               
                 TTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGT 
               
               
                   
               
               
                 GAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCG 
               
               
                   
               
               
                 AACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAA 
               
               
                   
               
               
                 CGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATT 
               
               
                   
               
               
                 ATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATT 
               
               
                   
               
               
                 CTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACG 
               
               
                   
               
               
                 GATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGA 
               
               
                   
               
               
                 TAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGC 
               
               
                   
               
               
                 TAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGT 
               
               
                   
               
               
                 TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCAC 
               
               
                   
               
               
                 GATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAAC 
               
               
                   
               
               
                 TACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGAT 
               
               
                   
               
               
                 AAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTAT 
               
               
                   
               
               
                 TGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAG 
               
               
                   
               
               
                 CACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACG 
               
               
                   
               
               
                 GGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGG 
               
               
                   
               
               
                 TGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATA 
               
               
                   
               
               
                 TACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTG 
               
               
                   
               
               
                 AAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTC 
               
               
                   
               
               
                 GTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAG 
               
               
                   
               
               
                 ATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCG 
               
               
                   
               
               
                 CTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCC 
               
               
                   
               
               
                 GAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAG 
               
               
                   
               
               
                 TGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACA 
               
               
                   
               
               
                 TACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAA 
               
               
                   
               
               
                 GTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGC 
               
               
                   
               
               
                 AGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA 
               
               
                   
               
               
                 ACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGC 
               
               
                   
               
               
                 CACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGG 
               
               
                   
               
               
                 TCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTAT 
               
               
                   
               
               
                 CTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTT 
               
               
                   
               
               
                 GTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGG 
               
               
                   
               
               
                 CCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 26-Representative FHL AAV Vector (with CAG Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAG 
               
               
                   
               
               
                 CCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGC 
               
               
                   
               
               
                 GCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGTT 
               
               
                   
               
               
                 GGCAAAGAATTCTGCAGTCGACGGTACCGCGGGCCCGGGATCCACCGGTC 
               
               
                   
               
               
                 GCCACCATGGTGCGCTCCTCCAAGAACGTCATCAAGGAGTTCATGCGCTT 
               
               
                   
               
               
                 CAAGGTGCGCATGGAGGGCACCGTGAACGGCCACGAGTTCGAGATCGAGG 
               
               
                   
               
               
                 GCGAGGGCGAGGGCCGCCCCTACGAGGGCCACAACACCGTGAAGCTGAAG 
               
               
                   
               
               
                 GTGACCAAGGGCGGCCCCCTGCCCTTCGCCTGGGACATCCTGTCCCCCCA 
               
               
                   
               
               
                 GTTCCAGTACGGCTCCAAGGTGTACGTGAAGCACCCCGCCGACATCCCCG 
               
               
                   
               
               
                 ACTACAAGAAGCTGTCCTTCCCCGAGGGCTTCAAGTGGGAGCGCGTGATG 
               
               
                   
               
               
                 AACTTCGAGGACGGCGGCGTGGTGACCGTGACCCAGGACTCCTCCCTGCA 
               
               
                   
               
               
                 GGACGGCTGCTTCATCTACAAGGTGAAGTTCATCGGCGTGAACTTCCCCT 
               
               
                   
               
               
                 CCGACGGCCCCGTAATGCAGAAGAAGACCATGGGCTGGGAGGCCTCCACC 
               
               
                   
               
               
                 GAGCGCCTGTACCCCCGCGACGGCGTGCTGAAGGGCGAGATCCACAAGGC 
               
               
                   
               
               
                 CCTGAAGCTGAAGGACGGCGGCCACTACCTGGTGGAGTTCAAGTCCATCT 
               
               
                   
               
               
                 ACATGGCCAAGAAGCCCGTGCAGCTGCCCGGCTACTACTACGTGGACTCC 
               
               
                   
               
               
                 AAGCTGGACATCACCTCCCACAACGAGGACTACACCATCGTGGAGCAGTA 
               
               
                   
               
               
                 CGAGCGCACCGAGGGCCGCCACCACCTGTTCCTGTAGCGGCCGCACTCCT 
               
               
                   
               
               
                 CAGGTGCAGGCTGCCTATCAGAAGGTGGTGGCTGGTGTGGCCAATGCCCT 
               
               
                   
               
               
                 GGCTCACAAATACCACTGAGATCTTTTTCCCTCTGCCAAAAATTATGGGG 
               
               
                   
               
               
                 ACATCATGAAGCCCCTTGAGCATCTGACTTCTGGCTAATAAAGGAAATTT 
               
               
                   
               
               
                 ATTTTCATTGCAATAGTGTGTTGGAATTTTTTGTGTCTCTCACTCGGAAG 
               
               
                   
               
               
                 GACATATGGGAGGGCAAATCACCGGTCTCGAAGGCCTGCAGGCGGCCGCC 
               
               
                   
               
               
                 GCCACCATGAATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTATGGG 
               
               
                   
               
               
                 CTATTTGTGTAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAATACA 
               
               
                   
               
               
                 GAAATTCTGACAGGTTCCTGGTCTGACCAAACATATCCAGAAGGCACCCA 
               
               
                   
               
               
                 GGCTATCTATAAATGCCGCCCTGGATATAGATCTCTTGGAAATGTAATAA 
               
               
                   
               
               
                 TGGTATGCAGGAAGGGAGAATGGGTTGCTCTTAATCCATTAAGGAAATGT 
               
               
                   
               
               
                 CAGAAAAGGCCCTGTGGACATCCTGGAGATACTCCTTTTGGTACTTTTAC 
               
               
                   
               
               
                 CCTTACAGGAGGAAATGTGTTTGAATATGGTGTAAAAGCTGTGTATACAT 
               
               
                   
               
               
                 GTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTACCGTGAATGTGAC 
               
               
                   
               
               
                 ACAGATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGAAGTGTTT 
               
               
                   
               
               
                 ACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATGGAAC 
               
               
                   
               
               
                 CAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGTAACTCA 
               
               
                   
               
               
                 GGCTACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATGGTTT 
               
               
                   
               
               
                 TTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCCCCAG 
               
               
                   
               
               
                 ATGTTATAAATGGATCTCCTATATCTCAGAAGATTATTTATAAGGAGAAT 
               
               
                   
               
               
                 GAACGATTTCAATATAAATGTAACATGGGTTATGAATACAGTGAAAGAGG 
               
               
                   
               
               
                 AGATGCTGTATGCACTGAATCTGGATGGCGTCCGTTGCCTTCATGTGAAG 
               
               
                   
               
               
                 AAAAATCATGTGATAATCCTTATATTCCAAATGGTGACTACTCACCTTTA 
               
               
                   
               
               
                 AGGATTAAACACAGAACTGGAGATGAAATCACGTACCAGTGTAGAAATGG 
               
               
                   
               
               
                 TTTTTATCCTGCAACCCGGGGAAATACAGCAAAATGCACAAGTACTGGCT 
               
               
                   
               
               
                 GGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGATTATCCAGACATT 
               
               
                   
               
               
                 AAACATGGAGGTCTATATCATGAGAATATGCGTAGACCATACTTTCCAGT 
               
               
                   
               
               
                 AGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACATTTTGAGACTC 
               
               
                   
               
               
                 CGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGATGGTCG 
               
               
                   
               
               
                 CCAGCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAAATGG 
               
               
                   
               
               
                 ATATAATCAAAATCATGGAAGAAAGTTTGTACAGGGTAAATCTATAGACG 
               
               
                   
               
               
                 TTGCCTGCCATCCTGGCTACGCTCTTCCAAAAGCGCAGACCACAGTTACA 
               
               
                   
               
               
                 TGTATGGAGAATGGCTGGTCTCCTACTCCCAGATGCATCCGTGTCAGCTT 
               
               
                   
               
               
                 TACCCTCTGATAAGATATCGATACATTGATGAGTTTGGACAAACCACAAC 
               
               
                   
               
               
                 TAGAATGCAGTGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCTATTG 
               
               
                   
               
               
                 CTTTATTTGTAACCATTATAAGCTGCAATAAACAAGATATCGTTAACTCG 
               
               
                   
               
               
                 AGGGATCCCACGTGCTGATTTTGTAGGTAACCACGTGCGGACCGAGCGGC 
               
               
                   
               
               
                 CGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGC 
               
               
                   
               
               
                 TCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGC 
               
               
                   
               
               
                 CCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGGCGCC 
               
               
                   
               
               
                 TGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATA 
               
               
                   
               
               
                 CGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCG 
               
               
                   
               
               
                 GGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGC 
               
               
                   
               
               
                 GCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCT 
               
               
                   
               
               
                 TTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGT 
               
               
                   
               
               
                 GCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTTCACG 
               
               
                   
               
               
                 TAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGT 
               
               
                   
               
               
                 CCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAAC 
               
               
                   
               
               
                 CCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGC 
               
               
                   
               
               
                 CTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTTTA 
               
               
                   
               
               
                 ACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGC 
               
               
                   
               
               
                 TCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGA 
               
               
                   
               
               
                 CGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTG 
               
               
                   
               
               
                 TGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCG 
               
               
                   
               
               
                 AAACGCGCGAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAA 
               
               
                   
               
               
                 TGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAA 
               
               
                   
               
               
                 ATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATG 
               
               
                   
               
               
                 TATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAA 
               
               
                   
               
               
                 AAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTT 
               
               
                   
               
               
                 TTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAA 
               
               
                   
               
               
                 GTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACT 
               
               
                   
               
               
                 GGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTT 
               
               
                   
               
               
                 TTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCC 
               
               
                   
               
               
                 CGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCA 
               
               
                   
               
               
                 GAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATG 
               
               
                   
               
               
                 GCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAAC 
               
               
                   
               
               
                 ACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAAC 
               
               
                   
               
               
                 CGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGG 
               
               
                   
               
               
                 AACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATG 
               
               
                   
               
               
                 CCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACT 
               
               
                   
               
               
                 TACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAG 
               
               
                   
               
               
                 TTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT 
               
               
                   
               
               
                 GATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACT 
               
               
                   
               
               
                 GGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGA 
               
               
                   
               
               
                 GTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCC 
               
               
                   
               
               
                 TCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACT 
               
               
                   
               
               
                 TTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGA 
               
               
                   
               
               
                 TCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC 
               
               
                   
               
               
                 CACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCC 
               
               
                   
               
               
                 TTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTAC 
               
               
                   
               
               
                 CAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAG 
               
               
                   
               
               
                 GTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTA 
               
               
                   
               
               
                 GCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACC 
               
               
                   
               
               
                 TCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG 
               
               
                   
               
               
                 TGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCG 
               
               
                   
               
               
                 GTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGA 
               
               
                   
               
               
                 CCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACG 
               
               
                   
               
               
                 CTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGG 
               
               
                   
               
               
                 AACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTT 
               
               
                   
               
               
                 ATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGA 
               
               
                   
               
               
                 TGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTT 
               
               
                   
               
               
                 TTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 27-Representative FHL AAV Vector (with CRALBP  
               
               
                 Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAG 
               
               
                   
               
               
                 CCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGC 
               
               
                   
               
               
                 GCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGAC 
               
               
                   
               
               
                 GCGTTAACTAGTACCCTGGTGGTGGTGGTGGGGGGGGGGGGGTGCTCTCT 
               
               
                   
               
               
                 CAGCAACCCCACCCCGGGATCTTGAGGAGAAAGAGGGCAGAGAAAAGAGG 
               
               
                   
               
               
                 GAATGGGACTGGCCCAGATCCCAGCCCCACAGCCGGGCTTCCACATGGCC 
               
               
                   
               
               
                 GAGCAGGAACTCCAGAGCAGGAGCACACAAAGGAGGGCTTTGATGCGCCT 
               
               
                   
               
               
                 CCAGCCAGGCCCAGGCCTCTCCCCTCTCCCCTTTCTCTCTGGGTCTTCCT 
               
               
                   
               
               
                 TTGCCCCACTGAGGGCCTCCTGTGAGCCCGATTTAACGGAAACTGTGGGC 
               
               
                   
               
               
                 GGTGAGAAGTTCCTTATGACACACTAATCCCAACCTGCTGACCGGACCAC 
               
               
                   
               
               
                 GCCTCCAGCGGAGGGAACCTCTAGAGCTCCAGGACATTCAGGTACCAGGT 
               
               
                   
               
               
                 AGCCCCAAGGAGGAGCTGCCGACCACCGGTCTCGAAGGCCTGCAGGCGGC 
               
               
                   
               
               
                 CGCCGCCACCATGAATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTA 
               
               
                   
               
               
                 TGGGCTATTTGTGTAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAA 
               
               
                   
               
               
                 TACAGAAATTCTGACAGGTTCCTGGTCTGACCAAACATATCCAGAAGGCA 
               
               
                   
               
               
                 CCCAGGCTATCTATAAATGCCGCCCTGGATATAGATCTCTTGGAAATGTA 
               
               
                   
               
               
                 ATAATGGTATGCAGGAAGGGAGAATGGGTTGCTCTTAATCCATTAAGGAA 
               
               
                   
               
               
                 ATGTCAGAAAAGGCCCTGTGGACATCCTGGAGATACTCCTTTTGGTACTT 
               
               
                   
               
               
                 TTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGTAAAAGCTGTGTAT 
               
               
                   
               
               
                 ACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTACCGTGAATG 
               
               
                   
               
               
                 TGACACAGATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGAAGT 
               
               
                   
               
               
                 GTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATG 
               
               
                   
               
               
                 GAACCAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGTAA 
               
               
                   
               
               
                 CTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATG 
               
               
                   
               
               
                 GTTTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCC 
               
               
                   
               
               
                 CCAGATGTTATAAATGGATCTCCTATATCTCAGAAGATTATTTATAAGGA 
               
               
                   
               
               
                 GAATGAACGATTTCAATATAAATGTAACATGGGTTATGAATACAGTGAAA 
               
               
                   
               
               
                 GAGGAGATGCTGTATGCACTGAATCTGGATGGCGTCCGTTGCCTTCATGT 
               
               
                   
               
               
                 GAAGAAAAATCATGTGATAATCCTTATATTCCAAATGGTGACTACTCACC 
               
               
                   
               
               
                 TTTAAGGATTAAACACAGAACTGGAGATGAAATCACGTACCAGTGTAGAA 
               
               
                   
               
               
                 ATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAAATGCACAAGTACT 
               
               
                   
               
               
                 GGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGATTATCCAGA 
               
               
                   
               
               
                 CATTAAACATGGAGGTCTATATCATGAGAATATGCGTAGACCATACTTTC 
               
               
                   
               
               
                 CAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACATTTTGAG 
               
               
                   
               
               
                 ACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGATG 
               
               
                   
               
               
                 GTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAA 
               
               
                   
               
               
                 ATGGATATAATCAAAATCATGGAAGAAAGTTTGTACAGGGTAAATCTATA 
               
               
                   
               
               
                 GACGTTGCCTGCCATCCTGGCTACGCTCTTCCAAAAGCGCAGACCACAGT 
               
               
                   
               
               
                 TACATGTATGGAGAATGGCTGGTCTCCTACTCCCAGATGCATCCGTGTCA 
               
               
                   
               
               
                 GCTTTACCCTCTGATAAGATATCGATACATTGATGAGTTTGGACAAACCA 
               
               
                   
               
               
                 CAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCT 
               
               
                   
               
               
                 ATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACAAGATATCGTTAA 
               
               
                   
               
               
                 CTCGAGGGATCCCACGTGCTGATTTTGTAGGTAACCACGTGCGGACCGAG 
               
               
                   
               
               
                 CGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGC 
               
               
                   
               
               
                 TCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCT 
               
               
                   
               
               
                 TTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGG 
               
               
                   
               
               
                 CGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCG 
               
               
                   
               
               
                 CATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGC 
               
               
                   
               
               
                 GGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCC 
               
               
                   
               
               
                 TAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCC 
               
               
                   
               
               
                 GGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATT 
               
               
                   
               
               
                 TAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTT 
               
               
                   
               
               
                 CACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTG 
               
               
                   
               
               
                 GAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACT 
               
               
                   
               
               
                 CAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGATTT 
               
               
                   
               
               
                 CGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAAT 
               
               
                   
               
               
                 TTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAAT 
               
               
                   
               
               
                 CTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCG 
               
               
                   
               
               
                 CTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAA 
               
               
                   
               
               
                 GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATC 
               
               
                   
               
               
                 ACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGG 
               
               
                   
               
               
                 TTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGG 
               
               
                   
               
               
                 GGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAA 
               
               
                   
               
               
                 TATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATT 
               
               
                   
               
               
                 GAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCC 
               
               
                   
               
               
                 TTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGT 
               
               
                   
               
               
                 GAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCG 
               
               
                   
               
               
                 AACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAA 
               
               
                   
               
               
                 CGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATT 
               
               
                   
               
               
                 ATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATT 
               
               
                   
               
               
                 CTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACG 
               
               
                   
               
               
                 GATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGA 
               
               
                   
               
               
                 TAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGC 
               
               
                   
               
               
                 TAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGT 
               
               
                   
               
               
                 TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCAC 
               
               
                   
               
               
                 GATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAAC 
               
               
                   
               
               
                 TACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGAT 
               
               
                   
               
               
                 AAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTAT 
               
               
                   
               
               
                 TGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAG 
               
               
                   
               
               
                 CACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACG 
               
               
                   
               
               
                 GGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGG 
               
               
                   
               
               
                 TGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATA 
               
               
                   
               
               
                 TACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTG 
               
               
                   
               
               
                 AAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTC 
               
               
                   
               
               
                 GTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAG 
               
               
                   
               
               
                 ATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCG 
               
               
                   
               
               
                 CTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCC 
               
               
                   
               
               
                 GAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAG 
               
               
                   
               
               
                 TGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACA 
               
               
                   
               
               
                 TACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAA 
               
               
                   
               
               
                 GTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGC 
               
               
                   
               
               
                 AGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA 
               
               
                   
               
               
                 ACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGC 
               
               
                   
               
               
                 CACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGG 
               
               
                   
               
               
                 TCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTAT 
               
               
                   
               
               
                 CTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTT 
               
               
                   
               
               
                 GTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGG 
               
               
                   
               
               
                 CCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 28-Representative FHL AAV Vector (with hRPE65  
               
               
                 Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAG 
               
               
                   
               
               
                 CCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGC 
               
               
                   
               
               
                 GCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGTA 
               
               
                   
               
               
                 TATTTATTGAAGTTTAATATTGTGTTTGTGATACAGAAGTATTTGCTTTA 
               
               
                   
               
               
                 ATTCTAAATAAAAATTTTATGCTTTTATTGCTGGTTTAAGAAGATTTGGA 
               
               
                   
               
               
                 TTATCCTTGTACTTTGAGGAGAAGTTTCTTATTTGAAATATTTTGGAAAC 
               
               
                   
               
               
                 AGGTCTTTTAATGTGGAAAGATAGATATTAATCTCCTCTTCTATTACTCT 
               
               
                   
               
               
                 CCAAGATCCAACAAAAGTGATTATACCCCCCAAAATATGATGGTAGTATC 
               
               
                   
               
               
                 TTATACTACCATCATTTTATAGGCATAGGGCTCTTAGCTGCAAATAATGG 
               
               
                   
               
               
                 AACTAACTCTAATAAAGCAGAACGCAAATATTGTAAATATTAGAGAGCTA 
               
               
                   
               
               
                 ACAATCTCTGGGATGGCTAAAGGATGGAGCTTGGAGGCTACCCAGCCAGT 
               
               
                   
               
               
                 AACAATATTCCGGGCTCCACTGTTGAATGGAGACACTACAACTGCCTTGG 
               
               
                   
               
               
                 ATGGGCAGAGATATTATGGATGCTAAGCCCCAGGTGCTACCATTAGGACT 
               
               
                   
               
               
                 TCTACCACTGTCCCTAACGGGTGGAGCCCATCACATGCCTATGCCCTCAC 
               
               
                   
               
               
                 TGTAAGGAAATGAAGCTACTGTTGTATATCTTGGGAAGCACTTGGATTAA 
               
               
                   
               
               
                 TTGTTATACAGTTTTGTTGAAGAAGACCCCTAGGGTAAGTAGCCATAACT 
               
               
                   
               
               
                 GCACACTAAATTTAAAATTGTTAATGAGTTTCTCAAAAAAAATGTTAAGG 
               
               
                   
               
               
                 TTGTTAGCTGGTATAGTATATATCTTGCCTGTTTTCCAAGGACTTCTTTG 
               
               
                   
               
               
                 GGCAGTACCTTGTCTGTGCTGGCAAGCAACTGAGACTTAATGAAAGAGTA 
               
               
                   
               
               
                 TTGGAGATATGAATGAATTGATGCTGTATACTCTCAGAGTGCCAAACATA 
               
               
                   
               
               
                 TACCAATGGACAAGAAGGTGAGGCAGAGAGCAGACAGGCATTAGTGACAA 
               
               
                   
               
               
                 GCAAAGATATGCAGAATTTCATTCTCAGCAAATCAAAAGTCCTCAACCTG 
               
               
                   
               
               
                 GTTGGAAGAATATTGGCACTGAATGGTATCAATAAGGTTGCTAGAGAGGG 
               
               
                   
               
               
                 TTAGAGGTGCACAATGTGCTTCCATAACATTTTATACTTCTCCAATCTTA 
               
               
                   
               
               
                 GCACTAATCAAACATGGTTGAATACTTTGTTTACTATAACTCTTACAGAG 
               
               
                   
               
               
                 TTATAAGATCTGTGAAGACAGGGACAGGGACAATACCCATCTCTGTCTGG 
               
               
                   
               
               
                 TTCATAGGTGGTATGTAATAGATATTTTTAAAAATAAGTGAGTTAATGAA 
               
               
                   
               
               
                 TGAGGGTGAGAATGAAGGCACAGAGGTATTAGGGGGAGGTGGGCCCCAGA 
               
               
                   
               
               
                 GAATGGTGCCAAGGTCCAGTGGGGTGACTGGGATCAGCTCAGGCCTGACG 
               
               
                   
               
               
                 CTGGCCACTCCCACCTAGCTCCTTTCTTTCTAATCTGTTCTCATTCTCCT 
               
               
                   
               
               
                 TGGGAAGGATTGAGGTCTCTGGAAAACAGCCAAACAACTGTTATGGGAAC 
               
               
                   
               
               
                 AGCAAGCCCAAATAAAGCCAAGCATCAGGGGGATCTGAGAGCTGAAAGCA 
               
               
                   
               
               
                 ACTTCTGTTCCCCCTCCCTCAGCTGAAGGGGTGGGGAAGGGCTCCCAAAG 
               
               
                   
               
               
                 CCATAACTCCTTTTAAGGGATTTAGAAGGCATAAAAAGGCCCCTGGCTGA 
               
               
                   
               
               
                 GAACTTCCTTCTTCATTCTGCAGTACCGGTCTCGAAGGCCTGCAGGCGGC 
               
               
                   
               
               
                 CGCCGCCACCATGAATGAGACTTCTAGCAAAGATTATTTGCCTTATGTTA 
               
               
                   
               
               
                 TGGGCTATTTGTGTAGCAGAAGATTGCAATGAACTTCCTCCAAGAAGAAA 
               
               
                   
               
               
                 TACAGAAATTCTGACAGGTTCCTGGTCTGACCAAACATATCCAGAAGGCA 
               
               
                   
               
               
                 CCCAGGCTATCTATAAATGCCGCCCTGGATATAGATCTCTTGGAAATGTA 
               
               
                   
               
               
                 ATAATGGTATGCAGGAAGGGAGAATGGGTTGCTCTTAATCCATTAAGGAA 
               
               
                   
               
               
                 ATGTCAGAAAAGGCCCTGTGGACATCCTGGAGATACTCCTTTTGGTACTT 
               
               
                   
               
               
                 TTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGTAAAAGCTGTGTAT 
               
               
                   
               
               
                 ACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTACCGTGAATG 
               
               
                   
               
               
                 TGACACAGATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGAAGT 
               
               
                   
               
               
                 GTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGTGCAATG 
               
               
                   
               
               
                 GAACCAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATGTAA 
               
               
                   
               
               
                 CTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACGATG 
               
               
                   
               
               
                 GTTTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAATCC 
               
               
                   
               
               
                 CCAGATGTTATAAATGGATCTCCTATATCTCAGAAGATTATTTATAAGGA 
               
               
                   
               
               
                 GAATGAACGATTTCAATATAAATGTAACATGGGTTATGAATACAGTGAAA 
               
               
                   
               
               
                 GAGGAGATGCTGTATGCACTGAATCTGGATGGCGTCCGTTGCCTTCATGT 
               
               
                   
               
               
                 GAAGAAAAATCATGTGATAATCCTTATATTCCAAATGGTGACTACTCACC 
               
               
                   
               
               
                 TTTAAGGATTAAACACAGAACTGGAGATGAAATCACGTACCAGTGTAGAA 
               
               
                   
               
               
                 ATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAAATGCACAAGTACT 
               
               
                   
               
               
                 GGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGATTATCCAGA 
               
               
                   
               
               
                 CATTAAACATGGAGGTCTATATCATGAGAATATGCGTAGACCATACTTTC 
               
               
                   
               
               
                 CAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACATTTTGAG 
               
               
                   
               
               
                 ACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGGATG 
               
               
                   
               
               
                 GTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGGAAA 
               
               
                   
               
               
                 ATGGATATAATCAAAATCATGGAAGAAAGTTTGTACAGGGTAAATCTATA 
               
               
                   
               
               
                 GACGTTGCCTGCCATCCTGGCTACGCTCTTCCAAAAGCGCAGACCACAGT 
               
               
                   
               
               
                 TACATGTATGGAGAATGGCTGGTCTCCTACTCCCAGATGCATCCGTGTCA 
               
               
                   
               
               
                 GCTTTACCCTCTGATAAGATATCGATACATTGATGAGTTTGGACAAACCA 
               
               
                   
               
               
                 CAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCT 
               
               
                   
               
               
                 ATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACAAGATATCGTTAA 
               
               
                   
               
               
                 CTCGAGGGATCCCACGTGCTGATTTTGTAGGTAACCACGTGCGGACCGAG 
               
               
                   
               
               
                 CGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGC 
               
               
                   
               
               
                 TCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCT 
               
               
                   
               
               
                 TTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGG 
               
               
                   
               
               
                 CGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCG 
               
               
                   
               
               
                 CATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGC 
               
               
                   
               
               
                 GGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCC 
               
               
                   
               
               
                 TAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCC 
               
               
                   
               
               
                 GGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATT 
               
               
                   
               
               
                 TAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTT 
               
               
                   
               
               
                 CACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTG 
               
               
                   
               
               
                 GAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACT 
               
               
                   
               
               
                 CAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGATTT 
               
               
                   
               
               
                 CGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAAT 
               
               
                   
               
               
                 TTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAAT 
               
               
                   
               
               
                 CTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCG 
               
               
                   
               
               
                 CTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAA 
               
               
                   
               
               
                 GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATC 
               
               
                   
               
               
                 ACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGG 
               
               
                   
               
               
                 TTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGG 
               
               
                   
               
               
                 GGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAA 
               
               
                   
               
               
                 TATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATT 
               
               
                   
               
               
                 GAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCC 
               
               
                   
               
               
                 TTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGT 
               
               
                   
               
               
                 GAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCG 
               
               
                   
               
               
                 AACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAA 
               
               
                   
               
               
                 CGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATT 
               
               
                   
               
               
                 ATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATT 
               
               
                   
               
               
                 CTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACG 
               
               
                   
               
               
                 GATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGA 
               
               
                   
               
               
                 TAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGC 
               
               
                   
               
               
                 TAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGT 
               
               
                   
               
               
                 TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCAC 
               
               
                   
               
               
                 GATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAAC 
               
               
                   
               
               
                 TACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGAT 
               
               
                   
               
               
                 AAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTAT 
               
               
                   
               
               
                 TGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAG 
               
               
                   
               
               
                 CACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACG 
               
               
                   
               
               
                 GGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGG 
               
               
                   
               
               
                 TGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATA 
               
               
                   
               
               
                 TACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTG 
               
               
                   
               
               
                 AAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTC 
               
               
                   
               
               
                 GTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAG 
               
               
                   
               
               
                 ATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCG 
               
               
                   
               
               
                 CTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCC 
               
               
                   
               
               
                 GAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAG 
               
               
                   
               
               
                 TGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACA 
               
               
                   
               
               
                 TACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAA 
               
               
                   
               
               
                 GTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGC 
               
               
                   
               
               
                 AGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA 
               
               
                   
               
               
                 ACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGC 
               
               
                   
               
               
                 CACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGG 
               
               
                   
               
               
                 TCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTAT 
               
               
                   
               
               
                 CTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTT 
               
               
                   
               
               
                 GTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGG 
               
               
                   
               
               
                 CCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 29-Representative FHL AAV Vector (with HSP70  
               
               
                 Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAG 
               
               
                   
               
               
                 CCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGC 
               
               
                   
               
               
                 GCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGTT 
               
               
                   
               
               
                 AACTAGTCCTGCAGGGCCGCCCACTCCCCCTTCCTCTCAGGGTCCCTGTC 
               
               
                   
               
               
                 CCCTCCAGTGAATCCCAGAAGACTCTGGAGAGTTCTGAGCAGGGGGCGGC 
               
               
                   
               
               
                 ACTCTGGCCTCTGATTGGTCCAAGGAAGGCTGGGGGGCAGGACGGGAGGC 
               
               
                   
               
               
                 GAAAACCCTGGAATATTCCCGACCTGGCAGCCTCATCGAGCTCGGTGATT 
               
               
                   
               
               
                 GGCTCAGAAGGGAAAAGGCGGGTCTCCGTGACGACTTATAAAAGCCCAGG 
               
               
                   
               
               
                 GGCAAGCGGTCCGGATAACGGCTAGCCTGAGGAGCTGCTGCGACAGTCCA 
               
               
                   
               
               
                 CTACCTTTTTCGAGAGTGACTCCCGTTGTCCCAAGGCTTCCCAGAGCGAA 
               
               
                   
               
               
                 CCTGTGCGGCTGCAGGCACCGGCGCGTCGAGTTTCCGGCGTCCGGAAGGA 
               
               
                   
               
               
                 CCGAGCTCTTCTCGCGGATCCAGTGTTCCGTTTCCAGCCCCCAATCTCAG 
               
               
                   
               
               
                 AGCGGAGCCGACAGAGAGCAGGGAACCACCGGTCTCGAAGGCCTGCAGGC 
               
               
                   
               
               
                 GGCCGCCGCCACCATGAATGAGACTTCTAGCAAAGATTATTTGCCTTATG 
               
               
                   
               
               
                 TTATGGGCTATTTGTGTAGCAGAAGATTGCAATGAACTTCCTCCAAGAAG 
               
               
                   
               
               
                 AAATACAGAAATTCTGACAGGTTCCTGGTCTGACCAAACATATCCAGAAG 
               
               
                   
               
               
                 GCACCCAGGCTATCTATAAATGCCGCCCTGGATATAGATCTCTTGGAAAT 
               
               
                   
               
               
                 GTAATAATGGTATGCAGGAAGGGAGAATGGGTTGCTCTTAATCCATTAAG 
               
               
                   
               
               
                 GAAATGTCAGAAAAGGCCCTGTGGACATCCTGGAGATACTCCTTTTGGTA 
               
               
                   
               
               
                 CTTTTACCCTTACAGGAGGAAATGTGTTTGAATATGGTGTAAAAGCTGTG 
               
               
                   
               
               
                 TATACATGTAATGAGGGGTATCAATTGCTAGGTGAGATTAATTACCGTGA 
               
               
                   
               
               
                 ATGTGACACAGATGGATGGACCAATGATATTCCTATATGTGAAGTTGTGA 
               
               
                   
               
               
                 AGTGTTTACCAGTGACAGCACCAGAGAATGGAAAAATTGTCAGTAGTGCA 
               
               
                   
               
               
                 ATGGAACCAGATCGGGAATACCATTTTGGACAAGCAGTACGGTTTGTATG 
               
               
                   
               
               
                 TAACTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCATTGTTCAGACG 
               
               
                   
               
               
                 ATGGTTTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAATTTCATGCAAA 
               
               
                   
               
               
                 TCCCCAGATGTTATAAATGGATCTCCTATATCTCAGAAGATTATTTATAA 
               
               
                   
               
               
                 GGAGAATGAACGATTTCAATATAAATGTAACATGGGTTATGAATACAGTG 
               
               
                   
               
               
                 AAAGAGGAGATGCTGTATGCACTGAATCTGGATGGCGTCCGTTGCCTTCA 
               
               
                   
               
               
                 TGTGAAGAAAAATCATGTGATAATCCTTATATTCCAAATGGTGACTACTC 
               
               
                   
               
               
                 ACCTTTAAGGATTAAACACAGAACTGGAGATGAAATCACGTACCAGTGTA 
               
               
                   
               
               
                 GAAATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAAAATGCACAAGT 
               
               
                   
               
               
                 ACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAACCTTGTGATTATCC 
               
               
                   
               
               
                 AGACATTAAACATGGAGGTCTATATCATGAGAATATGCGTAGACCATACT 
               
               
                   
               
               
                 TTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTGTGATGAACATTTT 
               
               
                   
               
               
                 GAGACTCCGTCAGGAAGTTACTGGGATCACATTCATTGCACACAAGATGG 
               
               
                   
               
               
                 ATGGTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTTTCCTTATTTGG 
               
               
                   
               
               
                 AAAATGGATATAATCAAAATCATGGAAGAAAGTTTGTACAGGGTAAATCT 
               
               
                   
               
               
                 ATAGACGTTGCCTGCCATCCTGGCTACGCTCTTCCAAAAGCGCAGACCAC 
               
               
                   
               
               
                 AGTTACATGTATGGAGAATGGCTGGTCTCCTACTCCCAGATGCATCCGTG 
               
               
                   
               
               
                 TCAGCTTTACCCTCTGATAAGATATCGATACATTGATGAGTTTGGACAAA 
               
               
                   
               
               
                 CCACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAAATTTGTGAT 
               
               
                   
               
               
                 GCTATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACAAGATATCGT 
               
               
                   
               
               
                 TAACTCGAGGGATCCCACGTGCTGATTTTGTAGGTAACCACGTGCGGACC 
               
               
                   
               
               
                 GAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCG 
               
               
                   
               
               
                 CGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGG 
               
               
                   
               
               
                 GCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAG 
               
               
                   
               
               
                 GGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACA 
               
               
                   
               
               
                 CCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAG 
               
               
                   
               
               
                 CGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCG 
               
               
                   
               
               
                 CCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTC 
               
               
                   
               
               
                 GCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCG 
               
               
                   
               
               
                 ATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATG 
               
               
                   
               
               
                 GTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACG 
               
               
                   
               
               
                 TTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAAC 
               
               
                   
               
               
                 ACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGA 
               
               
                   
               
               
                 TTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCG 
               
               
                   
               
               
                 AATTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTAC 
               
               
                   
               
               
                 AATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACAC 
               
               
                   
               
               
                 CCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGA 
               
               
                   
               
               
                 CAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTC 
               
               
                   
               
               
                 ATCACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACGCCTATTTTTAT 
               
               
                   
               
               
                 AGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTT 
               
               
                   
               
               
                 CGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTC 
               
               
                   
               
               
                 AAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAAT 
               
               
                   
               
               
                 ATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATT 
               
               
                   
               
               
                 CCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCT 
               
               
                   
               
               
                 GGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACA 
               
               
                   
               
               
                 TCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAA 
               
               
                   
               
               
                 GAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGT 
               
               
                   
               
               
                 ATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACT 
               
               
                   
               
               
                 ATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTT 
               
               
                   
               
               
                 ACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAG 
               
               
                   
               
               
                 TGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGG 
               
               
                   
               
               
                 AGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGAT 
               
               
                   
               
               
                 CGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACAC 
               
               
                   
               
               
                 CACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCG 
               
               
                   
               
               
                 AACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCG 
               
               
                   
               
               
                 GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTT 
               
               
                   
               
               
                 TATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTG 
               
               
                   
               
               
                 CAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACG 
               
               
                   
               
               
                 ACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGAT 
               
               
                   
               
               
                 AGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCAT 
               
               
                   
               
               
                 ATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAG 
               
               
                   
               
               
                 GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTT 
               
               
                   
               
               
                 TTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTT 
               
               
                   
               
               
                 GAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCA 
               
               
                   
               
               
                 CCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTT 
               
               
                   
               
               
                 TCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTC 
               
               
                   
               
               
                 TAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCT 
               
               
                   
               
               
                 ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGA 
               
               
                   
               
               
                 TAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGG 
               
               
                   
               
               
                 CGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAG 
               
               
                   
               
               
                 CGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAG 
               
               
                   
               
               
                 CGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCA 
               
               
                   
               
               
                 GGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGG 
               
               
                   
               
               
                 TATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATT 
               
               
                   
               
               
                 TTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACG 
               
               
                   
               
               
                 CGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 30-Representative FHL AAV Vector (with PCK1  
               
               
                 Promoter) 
               
               
                 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAG 
               
               
                   
               
               
                 CCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGC 
               
               
                   
               
               
                 GCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGAG 
               
               
                   
               
               
                 CCCCCAGTTAGGTTAGGCATTTCCAATCTTTGCCAATAAGCCACATATTT 
               
               
                   
               
               
                 GCCCAAGTTAGGGTGCATCCTTCCCATGAACTTTGACTGTGACCTTTGAC 
               
               
                   
               
               
                 TATGGGGTGACATCTTATAGCTGTGGTGTTTTGCCAACCAGCAGCTCTTG 
               
               
                   
               
               
                 GTACACAAAATGTGCTGCTAGCAGGTGCCCCGGCCAACCTTGTCCTTGAC 
               
               
                   
               
               
                 CCACCTGCCTGTTAAGAAAAGGGTGTTGTGTTTTGCAACAGCAGTAAAAT 
               
               
                   
               
               
                 GGGTCAAGGTTTAGTCAGTTGGAAGTTGTGTCAAAACTCACTATGGTTGG 
               
               
                   
               
               
                 TTGAGGGCTCGAAGTCTCCCAGCATTCATTAACAACTATCTGTTCAATGA 
               
               
                   
               
               
                 TTATCTCCCTGGGGCGTGTTGCAGTGAGTTGGCCCAAAGCATAACTGACC 
               
               
                   
               
               
                 CTGGCCGTGATCCAGAGACCTGCCCCCTGACGTCAGTGGCGAGCCTCCCT 
               
               
                   
               
               
                 GGGTGCAGCTGAGGGGCAGGGCTATTCTTTTCCACAGTACCGGTCTCGAA 
               
               
                   
               
               
                 GGCCTGCAGGCGGCCGCCGCCACCATGAATGAGACTTCTAGCAAAGATTA 
               
               
                   
               
               
                 TTTGCCTTATGTTATGGGCTATTTGTGTAGCAGAAGATTGCAATGAACTT 
               
               
                   
               
               
                 CCTCCAAGAAGAAATACAGAAATTCTGACAGGTTCCTGGTCTGACCAAAC 
               
               
                   
               
               
                 ATATCCAGAAGGCACCCAGGCTATCTATAAATGCCGCCCTGGATATAGAT 
               
               
                   
               
               
                 CTCTTGGAAATGTAATAATGGTATGCAGGAAGGGAGAATGGGTTGCTCTT 
               
               
                   
               
               
                 AATCCATTAAGGAAATGTCAGAAAAGGCCCTGTGGACATCCTGGAGATAC 
               
               
                   
               
               
                 TCCTTTTGGTACTTTTACCCTTACAGGAGGAAATGTGTTTGAATATGGTG 
               
               
                   
               
               
                 TAAAAGCTGTGTATACATGTAATGAGGGGTATCAATTGCTAGGTGAGATT 
               
               
                   
               
               
                 AATTACCGTGAATGTGACACAGATGGATGGACCAATGATATTCCTATATG 
               
               
                   
               
               
                 TGAAGTTGTGAAGTGTTTACCAGTGACAGCACCAGAGAATGGAAAAATTG 
               
               
                   
               
               
                 TCAGTAGTGCAATGGAACCAGATCGGGAATACCATTTTGGACAAGCAGTA 
               
               
                   
               
               
                 CGGTTTGTATGTAACTCAGGCTACAAGATTGAAGGAGATGAAGAAATGCA 
               
               
                   
               
               
                 TTGTTCAGACGATGGTTTTTGGAGTAAAGAGAAACCAAAGTGTGTGGAAA 
               
               
                   
               
               
                 TTTCATGCAAATCCCCAGATGTTATAAATGGATCTCCTATATCTCAGAAG 
               
               
                   
               
               
                 ATTATTTATAAGGAGAATGAACGATTTCAATATAAATGTAACATGGGTTA 
               
               
                   
               
               
                 TGAATACAGTGAAAGAGGAGATGCTGTATGCACTGAATCTGGATGGCGTC 
               
               
                   
               
               
                 CGTTGCCTTCATGTGAAGAAAAATCATGTGATAATCCTTATATTCCAAAT 
               
               
                   
               
               
                 GGTGACTACTCACCTTTAAGGATTAAACACAGAACTGGAGATGAAATCAC 
               
               
                   
               
               
                 GTACCAGTGTAGAAATGGTTTTTATCCTGCAACCCGGGGAAATACAGCAA 
               
               
                   
               
               
                 AATGCACAAGTACTGGCTGGATACCTGCTCCGAGATGTACCTTGAAACCT 
               
               
                   
               
               
                 TGTGATTATCCAGACATTAAACATGGAGGTCTATATCATGAGAATATGCG 
               
               
                   
               
               
                 TAGACCATACTTTCCAGTAGCTGTAGGAAAATATTACTCCTATTACTGTG 
               
               
                   
               
               
                 ATGAACATTTTGAGACTCCGTCAGGAAGTTACTGGGATCACATTCATTGC 
               
               
                   
               
               
                 ACACAAGATGGATGGTCGCCAGCAGTACCATGCCTCAGAAAATGTTATTT 
               
               
                   
               
               
                 TCCTTATTTGGAAAATGGATATAATCAAAATCATGGAAGAAAGTTTGTAC 
               
               
                   
               
               
                 AGGGTAAATCTATAGACGTTGCCTGCCATCCTGGCTACGCTCTTCCAAAA 
               
               
                   
               
               
                 GCGCAGACCACAGTTACATGTATGGAGAATGGCTGGTCTCCTACTCCCAG 
               
               
                   
               
               
                 ATGCATCCGTGTCAGCTTTACCCTCTGATAAGATATCGATACATTGATGA 
               
               
                   
               
               
                 GTTTGGACAAACCACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTG 
               
               
                   
               
               
                 AAATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCTGCAATAAA 
               
               
                   
               
               
                 CAAGATATCGTTAACTCGAGGGATCCCACGTGCTGATTTTGTAGGTAACC 
               
               
                   
               
               
                 ACGTGCGGACCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACT 
               
               
                   
               
               
                 CCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGC 
               
               
                   
               
               
                 CCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCA 
               
               
                   
               
               
                 GCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGC 
               
               
                   
               
               
                 GGTATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTAGC 
               
               
                   
               
               
                 GGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTAC 
               
               
                   
               
               
                 ACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTC 
               
               
                   
               
               
                 TCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCT 
               
               
                   
               
               
                 TTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGA 
               
               
                   
               
               
                 TTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTC 
               
               
                   
               
               
                 GCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAA 
               
               
                   
               
               
                 ACTGGAACAACACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGG 
               
               
                   
               
               
                 GATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAA 
               
               
                   
               
               
                 AATTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTTTATGGTGC 
               
               
                   
               
               
                 ACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACA 
               
               
                   
               
               
                 CCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCAT 
               
               
                   
               
               
                 CCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGG 
               
               
                   
               
               
                 TTTTCACCGTCATCACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACG 
               
               
                   
               
               
                 CCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAG 
               
               
                   
               
               
                 GTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTC 
               
               
                   
               
               
                 TAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAAT 
               
               
                   
               
               
                 GCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTG 
               
               
                   
               
               
                 TCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCAC 
               
               
                   
               
               
                 CCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACG 
               
               
                   
               
               
                 AGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTT 
               
               
                   
               
               
                 TTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTA 
               
               
                   
               
               
                 TGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCG 
               
               
                   
               
               
                 CCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAG 
               
               
                   
               
               
                 AAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCC 
               
               
                   
               
               
                 ATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGG 
               
               
                   
               
               
                 AGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAA 
               
               
                   
               
               
                 CTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGAC 
               
               
                   
               
               
                 GAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACT 
               
               
                   
               
               
                 ATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACT 
               
               
                   
               
               
                 GGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCG 
               
               
                   
               
               
                 GCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCG 
               
               
                   
               
               
                 CGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAG 
               
               
                   
               
               
                 TTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAG 
               
               
                   
               
               
                 ATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCA 
               
               
                   
               
               
                 AGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTA 
               
               
                   
               
               
                 AAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCT 
               
               
                   
               
               
                 TAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAA 
               
               
                   
               
               
                 AGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAA 
               
               
                   
               
               
                 CAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTA 
               
               
                   
               
               
                 CCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAA 
               
               
                   
               
               
                 TACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTG 
               
               
                   
               
               
                 TAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCT 
               
               
                   
               
               
                 GCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTT 
               
               
                   
               
               
                 ACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGC 
               
               
                   
               
               
                 CCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAG 
               
               
                   
               
               
                 CTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCC 
               
               
                   
               
               
                 GGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGG 
               
               
                   
               
               
                 GAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTT 
               
               
                   
               
               
                 GAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAA 
               
               
                   
               
               
                 CGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTG 
               
               
                   
               
               
                 CTCACATGT 
               
               
                   
               
               
                 SEQ ID NO: 31-CAG Promoter 
               
               
                 GTTAACTTGGCAAAGAATTCTGCAGTCGACGGTACCGCGGGCCCGGGATCCACC 
               
               
                   
               
               
                 GGTCGCCACCATGGTGCGCTCCTCCAAGAACGTCATCAAGGAGTTCATGCGCTTC 
               
               
                   
               
               
                 AAGGTGCGCATGGAGGGCACCGTGAACGGCCACGAGTTCGAGATCGAGGGCGA 
               
               
                   
               
               
                 GGGCGAGGGCCGCCCCTACGAGGGCCACAACACCGTGAAGCTGAAGGTGACCAA 
               
               
                   
               
               
                 GGGCGGCCCCCTGCCCTTCGCCTGGGACATCCTGTCCCCCCAGTTCCAGTACGGC 
               
               
                   
               
               
                 TCCAAGGTGTACGTGAAGCACCCCGCCGACATCCCCGACTACAAGAAGCTGTCCT 
               
               
                   
               
               
                 TCCCCGAGGGCTTCAAGTGGGAGCGCGTGATGAACTTCGAGGACGGCGGCGTGG 
               
               
                   
               
               
                 TGACCGTGACCCAGGACTCCTCCCTGCAGGACGGCTGCTTCATCTACAAGGTGAA 
               
               
                   
               
               
                 GTTCATCGGCGTGAACTTCCCCTCCGACGGCCCCGTAATGCAGAAGAAGACCATG 
               
               
                   
               
               
                 GGCTGGGAGGCCTCCACCGAGCGCCTGTACCCCCGCGACGGCGTGCTGAAGGGC 
               
               
                   
               
               
                 GAGATCCACAAGGCCCTGAAGCTGAAGGACGGCGGCCACTACCTGGTGGAGTTC 
               
               
                   
               
               
                 AAGTCCATCTACATGGCCAAGAAGCCCGTGCAGCTGCCCGGCTACTACTACGTGG 
               
               
                   
               
               
                 ACTCCAAGCTGGACATCACCTCCCACAACGAGGACTACACCATCGTGGAGCAGT 
               
               
                   
               
               
                 ACGAGCGCACCGAGGGCCGCCACCACCTGTTCCTGTAGCGGCCGCACTCCTCAG 
               
               
                   
               
               
                 GTGCAGGCTGCCTATCAGAAGGTGGTGGCTGGTGTGGCCAATGCCCTGGCTCACA 
               
               
                   
               
               
                 AATACCACTGAGATCTTTTTCCCTCTGCCAAAAATTATGGGGACATCATGAAGCC 
               
               
                   
               
               
                 CCTTGAGCATCTGAcTTCTGGCTAATAAAGGAAATTTATTTTCATTGCAATAGTGT 
               
               
                   
               
               
                 GTTGGAATTTTTTGTGTCTCTCACTCGGAAGGACATATGGGAGGGCAAATC 
               
               
                   
               
               
                 SEQ ID NO: 32-hRPE65 Promoter 
               
               
                 GTTAACTATATTTATTGAAGTTTAATATTGTGTTTGTGATACAGAAGTATTTGCTT 
               
               
                   
               
               
                 TAATTCTAAATAAAAATTTTATGCTTTTATTGCTGGTTTAAGAAGATTTGGATTAT 
               
               
                   
               
               
                 CCTTGTACTTTGAGGAGAAGTTTCTTATTTGAAATATTTTGGAAACAGGTCTTTTA 
               
               
                   
               
               
                 ATGTGGAAAGATAGATATTAATCTCCTCTTCTATTACTCTCCAAGATCCAACAAA 
               
               
                   
               
               
                 AGTGATTATACCCCCCAAAATATGATGGTAGTATCTTATACTACCATCATTTTATA 
               
               
                   
               
               
                 GGCATAGGGCTCTTAGCTGCAAATAATGGAACTAACTCTAATAAAGCAGAACGC 
               
               
                   
               
               
                 AAATATTGTAAATATTAGAGAGCTAACAATCTCTGGGATGGCTAAAGGATGGAG 
               
               
                   
               
               
                 CTTGGAGGCTACCCAGCCAGTAACAATATTCCGGGCTCCACTGTTGAATGGAGAC 
               
               
                   
               
               
                 ACTACAACTGCCTTGGATGGGCAGAGATATTATGGATGCTAAGCCCCAGGTGCTA 
               
               
                   
               
               
                 CCATTAGGACTTCTACCACTGTCCCTAACGGGTGGAGCCCATCACATGCCTATGC 
               
               
                   
               
               
                 CCTCACTGTAAGGAAATGAAGCTACTGTTGTATATCTTGGGAAGCACTTGGATTA 
               
               
                   
               
               
                 ATTGTTATACAGTTTTGTTGAAGAAGACCCCTAGGGTAAGTAGCCATAACTGCAC 
               
               
                   
               
               
                 ACTAAATTTAAAATTGTTAATGAGTTTCTCAAAAAAAATGTTAAGGTTGTTAGCT 
               
               
                   
               
               
                 GGTATAGTATATATCTTGCCTGTTTTCCAAGGACTTCTTTGGGCAGTACCTTGTCT 
               
               
                   
               
               
                 GTGCTGGCAAGCAACTGAGACTTAATGAAAGAGTATTGGAGATATGAATGAATT 
               
               
                   
               
               
                 GATGCTGTATACTCTCAGAGTGCCAAACATATACCAATGGACAAGAAGGTGAGG 
               
               
                   
               
               
                 CAGAGAGCAGACAGGCATTAGTGACAAGCAAAGATATGCAGAATTTCATTCTCA 
               
               
                   
               
               
                 GCAAATCAAAAGTCCTCAACCTGGTTGGAAGAATATTGGCACTGAATGGTATCA 
               
               
                   
               
               
                 ATAAGGTTGCTAGAGAGGGTTAGAGGTGCACAATGTGCTTCCATAACATTTTATA 
               
               
                   
               
               
                 CTTCTCCAATCTTAGCACTAATCAAACATGGTTGAATACTTTGTTTACTATAACTC 
               
               
                   
               
               
                 TTACAGAGTTATAAGATCTGTGAAGACAGGGACAGGGACAATACCCATCTCTGT 
               
               
                   
               
               
                 CTGGTTCATAGGTGGTATGTAATAGATATTTTTAAAAATAAGTGAGTTAATGAAT 
               
               
                   
               
               
                 GAGGGTGAGAATGAAGGCACAGAGGTATTAGGGGGAGGTGGGCCCCAGAGAAT 
               
               
                   
               
               
                 GGTGCCAAGGTCCAGTGGGGTGACTGGGATCAGCTCAGGCCTGACGCTGGCCAC 
               
               
                   
               
               
                 TCCCACCTAGCTCCTTTCTTTCTAATCTGTTCTCATTCTCCTTGGGAAGGATTGAG 
               
               
                   
               
               
                 GTCTCTGGAAAACAGCCAAACAACTGTTATGGGAACAGCAAGCCCAAATAAAGC 
               
               
                   
               
               
                 CAAGCATCAGGGGGATCTGAGAGCTGAAAGCAACTTCTGTTCCCCCTCCCTCAGC 
               
               
                   
               
               
                 TGAAGGGGTGGGGAAGGGCTCCCAAAGCCATAACTCCTTTTAAGGGATTTAGAA 
               
               
                   
               
               
                 GGCATAAAAAGGCCCCTGGCTGAGAACTTCCTTCTTCATTCTGCAGTTGG 
               
               
                   
               
               
                 SEQ ID NO: 33- CFH Amino Acid Sequence 
               
               
                 MRLLAKIICLMLWAICVAEDCNELPPRRNTEILTGSWSDQTYPEGTQAIYKCRPGYRS 
               
               
                   
               
               
                 LG 
               
               
                   
               
               
                 NVIMVCRKGEWVALNPLRKCQKRPCGHPGDTPFGTFTLTGGNVFEYGVKAVYTCN 
               
               
                   
               
               
                 EGYQLLGEINYRECDTDGWTNDIPICEVVKCLPVTAPENGKIVSSAMEPDREYHFGQ 
               
               
                   
               
               
                 AVRFVCNSGYKIEGDEEMHCSDDGFWSKEKPKCVEISCKSPDVINGSPISQKIIYKENE 
               
               
                   
               
               
                 RFQYKCNMGYEYSERGDAVCTESGWRPLPSCEEKSCDNPYIPNGDYSPLRIKHRTGD 
               
               
                   
               
               
                 EITYQCRNGFYPATRGNTAKCTSTGWIPAPRCTLKPCDYPDIKHGGLYHENMRRPYF 
               
               
                   
               
               
                 PVAVGKYYSYYCDEHFETPSGSYWDHIHCTQDGWSPAVPCLRKCYFPYLENGYNQN 
               
               
                   
               
               
                 YGRKFVQGKSIDVACHPGYALPKAQTTVTCMENGWSPTPRCIRVKTCSKSSIDIENGF 
               
               
                   
               
               
                 ISESQYTYALKEKAKYQCKLGYVTADGETSGSITCGKDGWSAQPTCIKSCDIPVFMN 
               
               
                   
               
               
                 ARTKNDFTWFKLNDTLDYECHDGYESNTGSTTGSIVCGYNGWSDLPICYERECELPK 
               
               
                   
               
               
                 IDVHLVPDRKKDQYKVGEVLKFSCKPGFTIVGPNSVQCYHFGLSPDLPICKEQVQSC 
               
               
                   
               
               
                 GPPPELLNGNVKEKTKEEYGHSEVVEYYCNPRFLMKGPNKIQCVDGEWTTLPVCIVE 
               
               
                   
               
               
                 ESTCGDIPELEHGWAQLSSPPYYYGDSVEFNCSESFTMIGHRSITCIHGVWTQLPQCV 
               
               
                   
               
               
                 AIDKLKKCKSSNLIILEEHLKNKKEFDHNSNIRYRCRGKEGWIHTVCINGRWDPEVNC 
               
               
                   
               
               
                 SMAQIQLCPPPPQIPNSHNMTTTLNYRDGEKVSVLCQENYLIQEGEEITCKDGRWQSI 
               
               
                   
               
               
                 PLCVEKIPCSQPPQIEHGTINSSRSSQESYAHGTKLSYTCEGGFRISEENETTCYMGKW 
               
               
                   
               
               
                 SSPPQCEGLPCKSPPEISHGVVAHMSDSYQYGEEVTYKCFEGFGIDGPAIAKCLGEKW 
               
               
                   
               
               
                 SHPPSCIKTDCLSLPSFENAIPMGEKKDVYKAGEQVTYTCATYYKMDGASNVTCINS 
               
               
                   
               
               
                 RWTGRPTCRDTSCVNPPTVQNAYIVSRQMSKYPSGERVRYQCRSPYEMFGDEEVMC 
               
               
                   
               
               
                 LNGNWTEPPQCKDSTGKCGPPPPIDNGDITSFPLSVYAPASSVEYQCQNLYQLEGNK 
               
               
                   
               
               
                 RITCRNGQWSEPPKCLHPCVISREIMENYNIALRWTAKQKLYSRTGESVEFVCKRGY 
               
               
                   
               
               
                 RLSSRSHTLRTTCWDGKLEYPTCAK 
               
               
                   
               
               
                 SEQ ID NO: 34- FHL1 Amino Acid Sequence 
               
               
                 MRLLAKIICLMLWAICVAEDCNELPPRRNTEILTGSWSDQTYPEGTQATYKCRPGYRS 
               
               
                   
               
               
                 LG 
               
               
                   
               
               
                 NVIMVCRKGEWVALNPLRKCQKRPCGHPGDTPFGTFTLTGGNVFEYGVKAVYTCN 
               
               
                   
               
               
                 EGYQLLGEINYRECDTDGWTNDIPICEVVKCLPVTAPENGKIVSSAMEPDREYHFGQ 
               
               
                   
               
               
                 AVRFVCNSGYKIEGDEEMHCSDDGFWSKEKPKCVEISCKSPDVINGSPISQKIIYKENE 
               
               
                   
               
               
                 RFQYKCNMGYEYSERGDAVCTESGWRPLPSCEEKSCDNPYIPNGDYSPLRIKHRTGD 
               
               
                   
               
               
                 EITYQCRNGFYPATRGNTAKCTSTGWIPAPRCTLKPCDYPDIKHGGLYHENMRRPYF 
               
               
                   
               
               
                 PVAVGKYYSYYCDEHFETPSGSYWDHIHCTQDGWSPAVPCLRKCYFPYLENGYNQN 
               
               
                   
               
               
                 YGRKFVQGKSIDVACHPGYALPKAQTTVTCMENGWSPTPRCIRVSFTL 
               
               
                   
               
               
                 SEQ ID NO: 35- CFI Amino Acid Sequence 
               
               
                 MKLLHVFLLFLCFHLRFCKVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIE 
               
               
                   
               
               
                 GTCVCKLPYQCPKNGTAVCATNRRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFS 
               
               
                   
               
               
                 VSLKHGNTDSEGIVEVKLVDQDKTMFICKSSWSMREANVACLDLGFQQGADTQRRF 
               
               
                   
               
               
                 KLSDLSINSTECLHVHCRGLETSLAECTFTKRRTMGYQDFADVVCYTQKADSPMDD 
               
               
                   
               
               
                 FFQCVNGKYISQMKACDGINDCGDQSDELCCKACQGKGFHCKSGVCIPSQYQCNGE 
               
               
                   
               
               
                 VDCITGEDEVGCAGFASVTQEETEILTADMDAERRRIKSLLPKLSCGVKNRMHIRRK 
               
               
                   
               
               
                 RIVGGKRAQLGDLPWQVAIKDASGITCGGIYIGGCWILTAAHCLRASKTHRYQIWTT 
               
               
                   
               
               
                 VVDWIHPDLKRIVIEYVDRIIFHENYNAGTYQNDIALIEMKKDGNKKDCELPRSIPAC 
               
               
                   
               
               
                 VPWSPYLFQPNDTCIVSGWGREKDNERVFSLQWGEVKLISNCSKFYGNRFYEKEME 
               
               
                   
               
               
                 CAGTYDGSIDACKGDSGGPLVCMDANNVTYVWGVVSWGENCGKPEFPGVYTKVA 
               
               
                   
               
               
                 NYFDWISYHVGRPFISQYNV 
               
               
                   
               
               
                 SEQ ID NO: 36- MECP Promoter Sequence 
               
               
                 GGCCGAAATGGACAGGAAATCTCGCCAATTGACGGCATCGCCGCTGAGACTCCC 
               
               
                   
               
               
                 CCCTCCCCCGTCCTCCCCGTCCCAGCCCGGCCATCACAGCCAATGACGGGCGGGC 
               
               
                   
               
               
                 TCGCAGCGGCGCCGAGGGCGGGGCGCGGGCGCGCAGGTGCAGCAGCGCGCGGG 
               
               
                   
               
               
                 CCGGCCAAGAGGGCGGGGCGCGACGTCGGCCGTGCGGGGTCCCGGCGTCGGCGG 
               
               
                   
               
               
                 CGCGCGC