Source: https://patents.google.com/patent/US9439960/en
Timestamp: 2018-02-25 21:47:33
Document Index: 300991804

Matched Legal Cases: ['§202', 'Application No. 60', 'Application No. 2008310713', 'Application No. 200880111084', 'Application No. 200880111084', 'Application No. 200880111084', 'Application No. 08836810', 'Application No. 08836810', 'application No. 196', 'application No. 196', 'art 2', 'Application No. 204850', 'Application No. 204850', 'Application No. 204850', 'Application No. 204850', 'Application No. 2010', 'Application No. 584459', 'Application No. 584459', 'Application No. 2012075594', 'Application No. 2010020808', 'Application No. 2010020808', 'Application No. 201002080']

US9439960B2 - Cytomegalovirus vaccines and methods of production - Google Patents
US9439960B2
US9439960B2 US12681504 US68150408A US9439960B2 US 9439960 B2 US9439960 B2 US 9439960B2 US 12681504 US12681504 US 12681504 US 68150408 A US68150408 A US 68150408A US 9439960 B2 US9439960 B2 US 9439960B2
US12681504
US20100285059A1 (en )
Pursuant to 35 U.S.C. §202(c), it is acknowledged that the United States government may have certain rights in the invention described herein, which was made in part with funds from the National Institutes of Health under Grant Nos.: CA85786, CA82396. AI54430 and GM71508.
This application is the U.S. National Stage of International Application No. PCT/US2008/079494, filed Oct. 10, 2008, which designates the U.S., published in English, and claims the benefit of U.S. Provisional Application No. 60/998,426, filed Oct. 10, 2007, the entire contents of which are incorporated by reference herein.
This application incorporates by reference the Sequence Listing contained in the following ASCII text file:
a) File name: 45611000002SUBSEQLIST6222016; created Jun. 22, 2016, 161 KB in size.
Cytomegalovirus (CMV) is a herpes virus classified as being a member of the beta subfamily of herpesviridae. According to the Centers for Disease Control and Prevention, CMV infection is found fairly ubiquitously in the human population, with an estimated 40-80% of the United States adult population infected. The virus is spread primarily through bodily fluids, and is frequently passed from pregnant mothers to the fetus or newborn. In most individuals. CMV infection is latent, although virus activation can result in high fever, chills, fatigue, headaches, nausea, and splenomegaly.
The entry of herpesviruses into cells is a complex process initiated by adsorption and receptor binding and followed by fusion of the virus envelope with a cell membrane. Fusion occurs at either the plasma membrane or an endosomal membrane. For instance, Epstein-Barr virus (EBV) enters primary B cells via receptor-mediated endocytosis (1, 2), yet it infects epithelial cells or transformed B cells by fusion of the virion envelope with the plasma membrane (1). Herpes simplex virus fuses with the plasma membrane of some cell types, but enters others by endocytosis (3-6). Human cytomegalovirus (HCMV) infects multiple cell types in vivo, including epithelial cells, endothelial cells and fibroblasts (7). It fuses with the plasma membranes of fibroblasts (8), but enters retinal pigmented epithelial cells and umbilical vein endothelial cells via endocytosis (9, 10).
The mechanism by which herpesviruses ‘choose’ their route of entry remains unclear. It is generally assumed that entry pathways are mainly determined by the host cell, but there is precedent for tropic roles of virion glycoproteins (11). EBV virions contain two gH complexes, gH/gL and gH/gL/gp42 (12, 13), which have mutually exclusive functions (11). Fusion with the plasma membrane of B cells is mediated by gH/gL/gp42 (14-16), but entry into epithelial cells is triggered by gH/gL (11, 12, 17). The cell type in which EBV is produced can alter its tropism. B-cell-derived EBV virions contain less gH-gL-gp42 than epithelial-cell-derived virions. As a result, B-cell-generated virus is more infectious for an epithelial cell and epithelial cell-derived virus is B cell tropic (18).
HCMV also encodes two gH/gL complexes: gH/gL/gO and gli/gL/pUL128/pUL130/pUL131 (19, 20). The gO-containing complex is sufficient for fibroblast infection, whereas the pUL128/pUL130/pUL131-containing complex is required to infect endothelial and epithelial cells (19-21). The AD169 laboratory strain contains only the gli/gL/gO complex in its virions (19). The absence of the second gH/gL complex is responsible for the loss of epithelial and endothelial cell tropism in HCMV laboratory strains (19-22).
Another aspect of the invention features a vaccine composition comprising a cytomegalovirus (CMV) population or virion components thereof, admixed with a suitable pharmaceutical carrier or adjuvant, wherein the CMV population is isolated from an cultured cells of a selected cell type. In one embodiment, the selected cell type is an epithelial cell type. In one embodiment, the vaccine composition comprises HCMV.
In various embodiments of the vaccine composition, the CMV population isolated from epithelial cell cultures is characterized by one or more features in subsequently infected host cells including but not limited to: (a) entry into the host cells by fusion with host cell plasma membranes; (b) greater virion-mediated cell-cell fusion of the host cells as compared with an equivalent CMV population isolated from cultured fibroblasts: (c) accelerated virus growth in the host cells as compared with an equivalent CMV population isolated from culture fibroblasts: (d) elicitation of a cellular response involving changes in expression greater than or equal to 2.5 fold of about two thirds fewer genes than a response elicited by an equivalent CMV population isolated from culture fibroblasts at 10 hours post-infection: or (e) elicitation of a cellular response involving a change in expression of one or more genes as shown in Table 2 and Table 4 herein, the latter being represented by GenBank Accession Nos: AK094860, NM_145023, NM_133492, NM_001039580, NM_001004301, NM_001034, AI369525, AK123066, NM_005345, NM_020731, BC071797, NM_003414, NM_000800, NM_138467, AK090803, AL133118, NM_001165, BG001037, NM_024861, NM_001043, NM_016239, NM_001018084, NM_001037442, NM_017600, NM_022097, NM_175868, NM_032266, NM_003841, NM_005039, NM_145051, NM_004294, AW856073, NM_024050, AF085968, NM_080927, NM_022115, AK056703, NM_000808, NM_012377, NM_006793, NM_031466, NM_005185, NM_139173, BX360933, NM_016125, NM_002104, NM_032188. NM_004185, NM_004843 or NM_173550.
FIG. 1. Kinetics of HCMV IE1 expression in ARPE-19 cells. (A) Infected cells (0.1 pfu/cell) were fixed at indicated times, and stained for IE1 (green in color photo, light gray in black and white photo), Sp100 (red in color photo, very dark gray in black and white photo) and DNA (blue in color photo, dark gray in black and white photo). (B) At various times after infection (0.1 pfu/cell), the percentage of IE1-expressing cells was quantified; results are shown on the graph.
FIG. 2. Electron microscopic analysis of HCMV entry into ARPE-19 cells, epiBADrUL131 or fibroBADrUL131 particles (50 pfu/cell) were bound to cells at 4° C. and then allowed to internalize at 37° C. for 15 min. Representative images are displayed.
FIG. 3. Effects of inhibitors of endosome acidification and virion source on HCMV entry into ARPE-19 cells. Experiments were performed in triplicate, and the number of positive cells in drug-treated relative to untreated cultures is reported. (A) Cells were pretreated with NH4Cl or BFA for 1 h, inoculated with epiBADrUL131 or fibroBADrUL131 (1 pfu/cell) and stained for IE1 16 h later. (B) Cells were pretreated with 50 mM NH4Cl or 40 BFA for 1 h. and then inoculated with BADrUL131 (0.1 pfu/cell) or FIXwt (0.01 pfu/cell) produced in the indicated cell types and stained for IE1 16 h later.
FIG. 4. Fusion from without of ARPE-19 cells induced by epithelial cell-derived virus. (A) Cells were inoculated with epiBADrUL131 or fibroBADrUL131 (20 pfu/cell) and then maintained in medium containing 200 μg/ml of PFA. Phase contrast images were taken at 16 h post infection. (B) A mixture of reporter and effector cells were infected by epiBADrUL131 or fibroBADrUL131 (20 pfu/cell) for at 4° C. for 1 h. The culture was then shifted to 37° C. for 6 h. after which relative luciferase activity was measured.
FIG. 5. Effect of pUL130-specific neutralizing antibody on HCMV infection and entry. (A) Epithelial cell- or fibroblast-derived viruses were incubated with various concentrations of anti-pUL130, and residual infectivity was determined. (B) Epithelial cell- or fibroblast-derived virus particles were pretreated with anti-pUL130 at a final concentration of 20 μg/ml or with PBS, and then adsorbed to ARPE-19 cells at 4° C. for 1 h. The cells were washed twice with cold PBS, and viral DNA associated with the cells was extracted to determine the relative numbers of particles attached to the cells. Alternatively, the cells were shifted to 37° C. for 2 h to allow the virus entry. Virions that did not penetrate the cells were removed by EDTA-trypsin treatment. Internalized viral DNA was subsequently quantified by real-time PCR.
FIG. 6. Modulation of the ARPE-19 transcriptome by HCMV produced in epithelial cells versus fibroblasts. (A) Venn diagrams depict the distribution of differentially regulated genes at 6 h or 10 hpi with epiBADrUL131 or fibroBADrUL131 (3 pfu/cell) relative to mock infection. (B) Changes in relative RNA levels assayed by real-time RT PCR. The genes tested are hydroxymethylbilane synthase (HMBS, NM_000190). GLI pathogenesis-related 1 (glioma) (GliPR, NM_006851), pentraxin-related gene, rapidly induced by IL-1 beta (PTX3, NM_002852), 2′-5′-oligoadenylate synthetase 3 (OAS3, NM_006187), interferon-induced protein 44 (IFI44, NM_006417), v-rel reticuloendotheliosis viral oncogene homolog B, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3 (relB, NM_006509), and ATP-binding cassette, sub-family C (CFTR/MRP), member 3 (MRP3, NM_003786).
A “coding region” of a gene consists of the nucleotide residues of the coding strand of the gene and the nucleotides of the non-coding strand of the gene which are homologous with or complementary to respectively, the coding region of an mRNA molecule which is produced by transcription of the gene.
The terms “conditioned virus.” “cell type-conditioned virus,” “conditioned CMV” or “cell type-conditioned CMV” refer to CMV that has been propagated in a selected cell type prior to its use in vaccine production, in accordance with the methods described herein. These terms are intended to be analogous to the term “conditioned medium.” which describes culture medium in which a particular cell type or cell line has been grown and then removed, and which contains components or factors produced by the cells, thereby altering the functionality of the medium. For purposes of the present application, the term “conditioned virus” similarly refers to virus that has been grown in a selected cell type and then removed from those cells, wherein the virus thereafter exhibits one or more altered functional features resulting from its growth in that cell type.
“Encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e. rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA. Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. Nucleotide sequences that encode proteins and RNA may include introns.
“Effective amount” or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a compound, formulation, material, or composition, as described herein effective to achieve a particular biological result. Such results may include, but are not limited to the inhibition of virus infection as determined by any means suitable in the art.
“Isolated” means altered or removed from the natural state. For example, a nucleic acid or a peptide naturally present in a living animal is not “isolated.” but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is “isolated.” An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell. Unless it is particularly specified otherwise herein, the proteins, virion complexes, antibodies and other biological molecules forming the subject matter of the present invention are isolated, or can be isolated.
“Parenteral” administration of an immunogenic or vaccine composition includes. e.g. subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, or infusion techniques.
The term “polynucleotide” as used herein is defined as a chain of nucleotides. Furthermore, nucleic acids are polymers of nucleotides. Thus, nucleic acids and polynucleotides as used herein are interchangeable. One skilled in the art has the general knowledge that nucleic acids are polynucleotides, which can be hydrolyzed into the monomeric “nucleotides.” The monomeric nucleotides can be hydrolyzed into nucleosides. As used herein polynucleotides include, but are not limited to, all nucleic acid sequences which are obtained by any means available in the art, including, without limitation, recombinant means. i.e. the cloning of nucleic acid sequences from a recombinant library or a cell genome, using ordinary cloning and amplification technology, and the like, and by synthetic means.
As used herein, the terms “peptide,” “polypeptide.” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprise a protein's or peptide's sequence. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. The polypeptides include natural peptides, recombinant peptides, synthetic peptides, or a combination thereof.
It has now been demonstrated in accordance with the present invention that the cell type in which CMV particles are produced has a profound influence on their behavior in subsequent rounds of infection. Thus, for example, while it was heretofore reported that that CMV enters epithelial cells by endocytosis, the present inventors have demonstrated that this is the mode of entry for CMV propagated in fibroblasts, but not for CMV propagated in cultured epithelial cells. Epithelial cell-propagated CMV enters epithelial cells predominantly via fusion with the plasma membrane. This different mode of entry has a variety of physiological consequences: it influences the kinetics with which the infection proceeds and it markedly influences the cellular response to infection. For instance virus grown in epithelial cells produces a dramatically muted cellular response as compared to cells infected with virus grown in fibroblasts. Many cellular anti-viral genes expressed alter infection with fibroblast-grown virus are not expressed after infection with epithelial cell-grown virus. As a consequence, CMV grown in epithelial cells is predicted to perform differently than does a vaccine than CMV grown in fibroblasts, thus offering a new and unexpected source of diversity for the generation of CMV vaccines. Likewise, propagation of CMV in other cell types, such as endothelial cells or specialized cell types that CMV is able to infect (e.g. neurons, other cells of the central or peripheral nervous systems, smooth muscle cells, hepatocytes, stromal cells, macrophages or dendritic cells) should produce additional novel sources of diversity for the generation of CMV vaccines.
The methods in accordance with an aspect of the invention comprise (1) providing a CMV strain or isolate; (2) propagating the strain or isolate in a cell culture of a selected cell type, and (3) harvesting CMV virions produced by growth in that cell type (referred to herein as “cell type-conditioned CMV”) for use in producing a CMV vaccine.
The cell type selected for propagating the CMV prior to its use for vaccine development can be any cell line permissive for CMV infection that produces a yield of virus particles. The virus particles might be highly infectious in some assays or the particles might exhibit limited or no infectivity in many assays. Suitable cell types include, but are not limited to, (1) epithelial cell lines such as ARPE-19, which is exemplified herein and other retinal pigmented epithelial cell lines. e.g., epithelial cell line K-1034 (Ando, Y. et al. 1997, Arch. Virol. 142(8): 1645-1658): HCMC, derived from normal human colonic mucosa (Smith, J D, 1986, J. Virol. 60(2): 583-588): Caco-2 intestinal epithelial cells (Esclatine. A. et al. 2000, J. of Virol. 74 (1): 513-51); SW480, HCT116, HeLa, H1299, and MCF-7 (regarding the latter five. see Wang. D. & T. Shenk, 2005. J. Virol. 79: 10330) (2) endothelial cell lines such as HMEC-1, a human microvascular endothelial line, immortalized with SV-40 virus large T antigen (Guetta. E. et al., 2001, Cardiovascular Research 50: 538-546); HUVEC and LMVEC (regarding the latter two, see Wang. D. & T. Shenk, 2005, J. Virol. 79: 10330); (3) neuronal cells such as SK-N-SH, SK-N-AS and IMR-32 (see Wang, D. & T. Shenk, 2005. J. Virol. 79: 10330) as well as primary epithelial, endothelial, smooth muscle, macrophage and dendritic cells derived from a variety of tissue/organ sources.
Any CMV or combination of CMVs amenable to development as a vaccine is suitable for use as a source of the CMV for the method, as long as they can be grown in at least one selected cell type. In one embodiment, the CMV is human CMV (HCMV), either an isolate that has been previously isolated and characterized or a new isolate of HCMV or an HCMV-like virus. In another embodiment, the CMV originates from another primate, including but not limited to chimpanzee (Davison, A J et al. 2003, J. Gen. Virol. 84: 17-28) and rhesus monkey (Hansen, S G et al. 2003. J. Virol. 77:6620-36: Rivailler, P et al. 2006. J. Virol. 80:4179-82). The CMV can be an unmodified virus from a selected source, or it can be a chimeric virus produced by genetic modification or combination of elements from two or more different CMV strains or isolates.
Methods of making chimeric viruses are known in the art. To this end, at least six strains of human CMV have been cloned as infectious bacterial artificial chromosomes (BAC) and sequenced (Murphy. E et al. 2003. Proc. Natl. Acad. Sci. USA 100: 14976-14981. The BAC sequences are available at GenBank Accession Nos. AC146999 (laboratory strain AD169, from which the BADrUL131 variant described herein was made): AC146851 (laboratory strain Towne): AC146904 (clinical isolate PH): AC146905 (clinical-like isolate Toledo): AC146906 (clinical isolate TR); and AC146907 (clinical isolate FIX). At least two strains of human CMV have been sequenced without prior BAC cloning, and are available at GenBank Accession Nos. BK000394 (laboratory strain AD169) and AY446894 (clinical isolate Merlin). The entire genome of a chimpanzee CMV strain is available at GenBank Accession No. AF480884. The genome sequence of two rhesus CMV strains is also available (Accession Nos. AY186194 and DQ205516). Utilizing the teachings of the present application, the skilled artisan would be able to use any of the aforementioned sequences, or any other publicly available CMV sequence to prepare chimeric CMVs or to otherwise genetically modify a CMV.
It has been demonstrated in accordance with the present invention that laboratory strains of CMV that have been passaged repeatedly in fibroblasts can be successfully conditioned by propagation on the selected cell line. For instance, as described in the Example herein. BADrUL131, a BAC clone of the repeatedly passaged AD169 HCMV strain in which the UL131 ORF has been repaired, was introduced by electroporation into cultured human foreskin fibroblasts, and the resulting virus preparation was amplified once in the epithelial cell line ARPE-19. Thus, various embodiments of the invention comprise the use of CMV (or the genomes of CMV) that has been passaged in a cell type that is different from the cell type selected for the conditioning step. For example, a CMV strain can be passaged multiple times in fibroblasts, then amplified in epithelial cells and thereafter used to produce a vaccine. It will be appreciated that the CMV can be amplified/propagated for one or more rounds in the selected cell type.
Mutagenesis can also be employed to attenuate a virus. For example, CMV virions can be exposed to ultraviolet or ionizing radiation or chemical mutagens, according to techniques known in the art. In addition to their use to produce chimeric viruses, recombinant techniques can also be used to produce attenuated CMV virions. For instance, site-directed mutagenesis, gene replacement, or gene knockout techniques can be used to derive virus strains with attenuated infectivity, pathogenicity or latency. An example of modifying a CMV by knockout mutagenesis is set forth in WO/2007/038316, which describes CMVs with genomes deleted in one or more latency-promoting genes, displaying an altered ability to enter or maintain a latent state.
The methods of the invention can be used to create combinations of CMVs propagated in different selected cell types, thereby conferring an additional level of diversity to the vaccines that are produced. In one embodiment, a single CMV isolate or strain is used to infect two or more different cultured cell lines of different types. e.g., retinal epithelial cells and endothelial cells. The CMV produced by amplification in the respective cell types is then combined for use in a single vaccine. In another embodiment, two or more different clinical isolates or strains of CMV are used to infect a single selected cell line, and the multi-strain or multi-isolate CMV population produced by amplification in that cell type is used to produce a vaccine. In yet another embodiment, multiple isolates or strains are used to infect two or more different cultured cell lines of different types, and the CMV populations produced by amplification in the respective cell types are combined for use in the vaccine.
In particular, CMV produced by propagation in epithelial cells have one or more of the following features, as compared with an equivalent strain or isolate of the virus produced by propagation in fibroblasts. First, as mentioned above, they can be distinguished by their entry into the host cells by fusion with host cell plasma membranes. CMV produced on epithelial cells also display greater virion-mediated cell-cell fusion of the host cells as compared with an equivalent CMV population isolated from cultured fibroblasts, as well as accelerated virus growth in the host cells as compared with an equivalent CMV population isolated from culture fibroblasts. In addition, they elicit a subdued cellular response as compared with equivalent CMV propagated in fibroblasts. At 10 hours post-infection about two-thirds fewer genes (˜50 versus ˜150 genes) exhibit a 2.5 fold or more change in expression level. In addition, epithelial-grown CMV can be characterized by the particular profile of host genes whose expression is changed (increased or decreased) following infection. These gene expression profiles are detailed in the Example, and can involve a change in expression of one or more genes represented by GenBank Accession Nos: AK094860. NM_145023, NM_133492. NM_001039580. NM_001004301, NM_001034, A1369525, AK123066, NM_005345, NM_020731, BC071797. NM_003414, NM_000800, NM_138467, AK090803, AL133118. NM_001165, BG001037. NM_024861, NM_001043, NM 016239, NM 001018084, NM_001037442, NM_017600, NM_022097, NM_175868, NM_032266, NM_003841, NM_005039, NM_145051, NM_004294, AW856073, NM_024050, AF085968, NM_080927, NM_022115, AK056703, NM_000808, NM_012377, NM_006793, NM_031466, NM_005185, NM_139173, BX360933, NM_016125, NM_002104, NM_032188, NM_004185, NM_004843 or NM_173550.
In this aspect of the invention, as in the foregoing aspects of the invention. CMV or a combination of CMVs amenable to development as a vaccine is suitable for use as a source of the aforementioned CMV population, as long as they can be grown in at least one epithelial cell line or another selected cell type. In one embodiment, the CMV is HCMV or an HCMV-like virus. In another embodiment, the CMV originates from another primate, including but not limited to chimpanzee and rhesus monkey, as described above. The CMV can be an unmodified virus from a selected source, or it can be a chimeric virus produced by genetic modification or combination of elements from two or more different CMV strains or isolates, as described above.
The vaccine composition can further comprise one or more adjuvants. Adjuvants can be any substance that enhances the immune response to the antigens in the vaccine. Non-limiting examples of adjuvants suitable for use in the present invention include Freund's adjuvant, incomplete Freund's adjuvant, saponin, surfactants such as hexadecylamine, octadecylamine, lysolecithin, demethyldioactadecyl ammonium bromide. N,N-dioctadecyl-N′—N-bis (2-hydroxyethylpropane diamine), methoxyhexa-decyl-glycerol, pluronic polyols, polyanions such as pyran, diethylaminoethyl (DEAE) dextran, dextran sulfate, polybrene, poly IC, polyacrylic acid, carbopol, ethylene maleic acid, aluminum hydroxide, and aluminum phosphate peptides, oil or hydrocarbon emulsions, and the like.
Vaccines can be formulated in aqueous solutions such as water or alcohol, or in physiologically compatible buffers such as Hanks' solution. Ringer's solution, or physiological saline buffer, including PBS. Vaccine formulations can also be prepared as solid form preparations which are intended to be converted, shortly before use, to liquid form preparations suitable for administration to a subject, for example, by constitution with a suitable vehicle, such as sterile water, saline solution, or alcohol, before use.
The vaccine compositions may further include one or more antioxidants. Exemplary reducing agents include mercaptopropionyl glycine, N-acetylcysteine, β-mercaptoethylamine, glutathione, ascorbic acid and its salts, sulfite, or sodium metabisulfite, or similar species. In addition, antioxidants can also include natural antioxidants such as vitamin E, C, leutein, xanthine, beta carotene and minerals such as zinc and selenium.
Vaccine compositions may further incorporate additional substances to function as stabilizing agents, preservatives, buffers, wetting agents, emulsifying agents, dispersing agents, and monosaccharides, polysaccharides, and salts for varying the osmotic balance. The vaccines can further comprise immunostimulatory molecules to enhance vaccine efficacy. Such molecules can potentiate the immune response, can induce inflammation, and can be any lymphokine or cytokine. Nonlimiting examples of cytokines include interleukin (IL)-1, IL-2, IL-3, IL-4, IL-12, IL-13, granulocyte-macrophage colony stimulating factor (GMCSF), macrophage inflammatory factor, and the like.
BADwt is derived from a BAC clone of the AD169 HCMV strain: BADrUL131 (19, 21) is a derivative of BADwt in which the UL1310RF has been repaired; BFXwt is derived from a BAC clone of the VR1814 clinical HCMV isolate. Viruses were prepared by electroporation of BAC DNAs into HFFs, and the resulting virus preparation was amplified once in ARPE-19 cells or HFFs, unless otherwise specified. Cell-free virions were partially purified by centrifugation through a sorbitol cushion and resuspended in serum-free medium. Virus titers were determined by plaque assay on MRC-5 cells. Neutralization of BADrUL131 was assayed by plaque reduction assay (19), by using purified anti-pUL130 monoclonal antibody (3E3) (19).
Anti-IE1 monoclonal antibody 1B12 was described previously (21). Rabbit anti-Sp100 polyclonal antibody (Chemicon) was used to visualize the ND10s.
ARPE-19 cells were exposed to virus at 4° C. for 1 h, unbound virus was removed by two washes with cold PBS, growth medium (37° C.) was added for 15 min. cells were rinsed with phosphate-buffered saline (PBS), fixed and processed for electron microscopy, and examined with an FEI Tecnai-T12 microscope at 80 kv.
ARPE-19 cells were pretreated with NH4Cl or Bafilomycin A1 (BFA) (Sigma) for 1 h at 37° C., followed by infection in the continued presence of the inhibitor. 16 h later, cultures were fixed in 2% paraformaldehyde and permeabilized with 0.1° A Triton X-100. IE1 was identified by immunofluorescence using monoclonal antibody 1B12 (21) plus Alexa 546-conjugated secondary antibody and nuclei were stained with DAPI. Inhibition was calculated as the percentage of IE1-expressing drug-treated relative to untreated cells.
A luciferase reporter assay was adapted to quantitatively analyze virion fusion activity. Reporter and effector ARPE-19 cells were prepared by electroporation (90-95% efficiency) with a plasmid carrying a luciferase gene under the control by a T7 promoter and a pcDNA3-T7 polymerase plasmid, respectively. At 24 h post transfection, the cells were mixed at a 1:1 ratio, and incubated at 37° C. for an additional 16 h. The mixed populations were then exposed to HCMV virions at 4° C. for 1 h, after which the monolayer was washed twice with cold PBS followed by addition of buffers (PBS with 10 mM 2-(N-morpholino)ethanesulfonic acid and 10 mM HEPES) with a final pH ranging of 4.5 to 8. After 3 min at 37° C. the buffers were removed, and normal growth medium was added. At 6 hpi, the cells were lysed, and luciferase activity was assayed using a luciferase reporter assay system (Promega).
Confluent ARPE-19 cells were serum starved for 24 h, followed by mock infection or infection. Total RNA was extracted at 6 or 10 hpi by using Trizol (Invitrogen), and purified with an RNeasy column (Qiagen). The RNA samples were amplified and labeled (cyanine-3) with the Agilent low RNA input fluorescent linear amplification kit. To control for chip to chip variation, a reference RNA (Clontech) was labeled (cyanine-5) and co-hybridized with the probes prepared from mock or HCMV-infected cells. The hybridization was performed in duplicate with Aligent Human 44K oligonucleotide arrays. Arrays were scanned using an Agilent scanner at 5 micron resolution, and images were analyzed with Agilent Feature Extraction software to determine the intensities of fluorescent signals for hybridized spots and for background subtraction. Agilent GeneSpring GX software was used for normalization and quantification of relative RNA changes.
The AD169 HCMV strain (BADwt) replicates poorly in ARPE-19 epithelial cells due to a mutation in its UL131 gene (10. 21). Repair of the mutation in AD169, producing BADrUL131, restores epithelial cell tropism (21) by allowing production of a gH/gL/pUL128/pUL130/pUL131 virion glycoprotein complex that is required for successful entry into these cells (19, 20).
BADrUL131 grown in ARPE-19 epithelial cells (epiBADrUL131) initiates its program of gene expression in epithelial cells more rapidly than BADrUL131 grown in HFF fibroblasts (fibroBADrUL131) (FIG. 1A). When ARPE-19 cells were infected with epiBADrUL131, ˜17% of the cells expressed detectable IE1 protein at 6 h post infection (hpi). IE1 expression was accompanied by disruption of ND10s in the nucleus. In contrast, infection with fibroBADrUL131 led to IE1 expression in only 2.8% of ARPE-19 cells at 6 hpi. The number of IE1-expressing cells, however, increased with time. There was no significant difference in the percentage of IE1-expressing ARPE-19 cells at 24 hpi with virus produced in the two cell types (FIG. 1B).
An electron microscopic examination of virus entry was performed to determine if the different kinetics of IE1 accumulation for ARPE-19 cell-derived virus versus HFF-derived virus resulted from an event prior to the onset of viral gene expression. ARPE-19 cells incubated with epiBADrUL131 or fibroBADrUL131 were permitted to attach at the cell surface at 4° C. and cultures were shifted to 37° C. for 15 min to allow internalization before processing for microscopy. For each sample, 40-50 cells were examined, with at least 90% of the cells showing either intact virions or capsids. The number of virus particles in each cell varied from 2-8, with most cells showing 2-3 particles.
In epiBADrUL131-infected ARPE-19 cells, virions were found almost exclusively at the cell surface, with about 97% of the virions at the apical membrane. Some particles were close to the cells but the section did not reveal evidence of contact (FIG. 2A, panel a), and others were captured in the process of fusion at the plasma membrane (FIG. 2A, panels b and c). Capsids beneath the inner surface of the membrane were observed rarely: in fact, only two examples were identified (FIG. 2A, panels d and e). No enveloped virions were found inside the cells. This result indicates that epiBADrUL131 enters the ARPE-19 cells by fusion with the plasma membrane. In contrast, fibroBADrUL131-infected cells contained virions at the cell membrane ˜65% of total) and inside the cell within vesicles ˜35% of total) (FIG. 2B). The particles within vesicles were enveloped, indicating they entered by endocytosis.
Infection of ARPE-19 Cells by Fibroblast—but not Epithelial Cell-Derived Virus is pH Dependent.
Many viruses that enter cells by endocytosis (1, 4, 10) require acidification of endosomes for the virion envelope to fuse with the endosomal membrane and release the capsid into the cytoplasm. NH4Cl, which buffers endosomal pH, and bafilomycin A1 (BFA), which blocks the endosomal ATPase proton pump, were tested for their effect on infection of ARPE-19 cells. After pretreatment with either agent, cells were infected and cultured in drug-containing medium for a further 1611. Successful infections were scored by assaying for IE1-positive cells. Consistent with the ultrastructural analysis described above, pretreatment with either agent had only a modest effect on epiBADrUL131 infection (FIG. 3A). In contrast, both agents inhibited IE1 expression after fibroBADrUL131 infection in a dose dependent manner, indicating that the entry of fibroblast-generated virus was dependent on endosomal acidification. The fact that the agents had little effect on entry by epiBADrUL131 shows that the inhibition of fibroBADrUL131 did not result from toxicity.
It was next determined whether virus grown in other types of epithelial cells and fibroblasts display the same properties as ARPE19- and HFF-derived virions. Virus stocks from hRPTEC epithelial cells and MRC-5 fibroblasts were used to infect ARPE-19 cells after treatment with NH4Cl or BFA, and they responded to the inhibitors exactly as did virus grown in ARPE-19 cells or HFFs (FIG. 3B, left panel). Thus. BADrUL131 produced in two different fibroblasts was substantially more sensitive to the inhibitors than virus produced in two different epithelial cell lines.
The effect of endosomal pH on entry of the BFXwt clinical isolate into ARPE-19 cells was also assayed (FIG. 3B, right panel). NH4Cl or BFA significantly reduced the number of IE1-positive ARPE-19 cells produced by infection with fibroblast-generated BFXwt, but only a slight inhibition was observed after infection with epithelial cell-derived BFXwt.
Mock-infected ARPE-19 cells exhibited no syncytia (FIG. 4A), and syncytia were rarely found after infection with fibroBADrUL131 (FIG. 4B). In contrast, after exposure to epiBADrUL131, cell-cell fusion was detected as early as 6 hpi, and 20-30% of the nuclei were aggregated in syncytia by 24 hpi (FIG. 4C). Cells were treated with PFA, which blocks progression to the late phase of infection, so the fusion must have been induced by epiBADrUL131 particles and not by newly expressed virion proteins.
A luciferase reporter assay was used to quantify the fusion activity of viral particles as well as the effects of pH on fusion from without. Reporter and effector cells received a plasmid containing a luciferase gene driven by a T7 promoter or a T7 RNA polymerase expression plasmid, respectively. The two ARPE-19 derivatives were mixed, and infection-dependent fusion was quantified by assaying luciferase expression, epiBADrUL131 consistently induced higher fusion activity than fibroBADrUL131 (FIG. 4D). At pH 7-8, the activity of fibroBADrUL131 was ˜3-fold lower than that of epiBADrUL131. When the cells were treated with low pH buffers after virus adsorption, both virus preparations mediated modestly enhanced fusion. BADwt did not induce fusion in this assay.
As discussed above, there is precedent for a herpesvirus to favor entering a specific cell type depending on the cell in which the infecting virus was produced. This phenomenon is different than the one that was observed as described above, i.e. HCMV preparations from different cell types enter epithelial cells by different mechanisms. Nevertheless, it remained possible that the different entry mechanisms would impact on the efficiency of replication and yield, resulting in a tropic effect. Therefore, experiments were conducted to determine whether the mode of entry influenced HCMV plaque production on epithelial cells as compared to fibroblasts (Table 1). Stocks of BADrUL131 were produced in ARPE-19, hRPTEC, HFF or MRC-5 cells and assayed for plaque formation on ARPE-19 or MRC-5 cells (Table 1). Although slightly more plaques were produced on ARPE-19 than MRC-5 cells, neither epithelial cell- nor fibroblast-derived virus preferentially generated plaques on one cell type compared to the other.
Titration of epithelial cell derived or fibroblast derived
BADrUL131 in ARPE19 and MRC5 cells (×105)
It has been reported previously that the gH/gL/pUL128/pUL130/pUL131 complex is dispensable for HCMV to be internalized by endothelial or epithelial cells, because laboratory strains lacking this complex are efficiently endocytosed (10). However, subsequent fusion with endosomal membrane and escape into the cytoplasm requires the complex. Consistent with these earlier results, the antibody to pUL130 did not block binding or internalization of epiBADrUL131, fibroBADrUL131 or BADwt when assayed on ARPE-19 cells (FIG. 5B). However, the total amount of internalized fibroblast-derived virus was lower than that of the epithelial cell-derived virus. This might reflect a reduced rate of internalization, which would be consistent with the delay in onset of IE1 expression by the fibroblast-derived virus (FIG. 1).
Differentially transcribed genes from epiBADrUL131-infected ARP19
cells at 6 h after infection
Differentially transcribed genes from fibroBADrUL131-infected ARP19
cells at 10 h after infection
AOP1; MER5; AOP-1; SP-22; PRO1748; MGC24293;
NM_006793 0.298 MGC104387
At 6 h after epiBADrUL131 infection, the levels of 47 RNAs were changed as compared to mock-infected cells, and 121 RNAs were altered in fibroBADrUL131-infected versus mock-infected cells. The set of modulated RNAs was substantially different for the two viruses: only 19 RNAs were altered after infection with either epiBADrUL131 or fibroBADrUL131. Although there might be several instances in which a gene was altered by one virus by a factor of ≧2.5-fold, while the other virus induced a more modest alteration that fell below the cut-off, inspection of the data revealed that this was not common. At 10 hpi, the number of host cell RNAs modulated by epiBADrUL131 increased only slightly (50 RNAs), whereas a more substantial increase was observed for fibroBADrUL131 (153 RNAs). At the later time, the number of RNAs modulated by both viruses increased to a limited extent (28 RNAs). The microarray results were confirmed by real time RT-PCR for one RNA that was not altered and six RNAs that were altered by infection (FIG. 6B).
To further compare the modulation of RNA levels by fibroBADrUL131 versus epiBADrUL131, the array results were filtered using a gene list comprised of four Gene Ontology groups: host-pathogen interaction (GO:0030383), cell communication (GO:0007154), viral life cycle (GO:0016032) and cell-cell signaling (GO:0007267). Nearly one third of the mRNAs (70 of 222) that were regulated greater than 2.5 fold in fibroBADrUL131-infected ARPE-19 cells were present in the combined grouping (Table 6). In marked contrast, only one of 86 RNAs induced by epiBADrUL131 was found in these four Gene Ontology groups. The two virus preparations generated substantially different transcriptional responses upon infection of epithelial cells.
Change Fold Change
Genbank 6 hpi 10 hpi Gene Name
NL2; ARP4; FIAF; PGAR; HFARP; pp1158;
NM_139314 6.679 2.067 ANGPTL2
RIG-1; FLJ13599; DKFZp434J1111;
Four GO groups were combined: host-pathogen interaction (GO: 0030383), cell communication (GO: 0007154), viral life cycle (GO: 0016032) and cell-cell signaling (GO: 0007267). The set of 9276 genes was used to filter array results from fibroBADrUL131-infected ARPE-19 cells. Genbank identifiers and gene names are shown along with the fold induction or repression at 6 and 10 hpi.
Probe sets that did not change by ≧2.5 compared to mock-infected cells are designated by “nc” for no change.
Virus grown in fibroblasts induces IE1 protein accumulation in ARPE-19 cells after a delay relative to virus from epithelial cells, suggesting that some aspect of entry by endocytosis proceeds more slowly than entry by fusion at the plasma membrane. Many virions are evident in endosomes, but no capsids were seen in the cytoplasm after entry of fibroblast-generated virus; and capsids were found rarely in the cytoplasm of cells infected with epithelial cell-produced virus. Apparently, virions linger for a time in endosomes, but once a capsid is freed of its envelope and reaches the cytoplasm, it is rapidly disassembled.
How are HCMV virions produced in the two cell types different? It appears different “fusion from without” activities provide an indication. Not only did epiBADrUL131 induce fusion more efficiently than fibroBADrUL131, but lowered pH enhanced the activities of both virus preparations. Without intending to be bound or limited by any explanation of mechanism, it is possible that fusion of membranes requires a threshold of fusion activity. The ability of pUL130 antibody to neutralize both virus preparations indicates that both depend on the gH/gL/pUL128/pUL130/pUL131 complex for fusion, so experiments were devised to the hypothesis that the viruses contain different amounts of the complex. Several of its constituents were assayed, and it was found that a slightly higher ratio (˜2-fold) of gH/gL/pUL128/pUL130/pUL131 to gH/gL/gO were present in epiBADrUL131 particles than in fibroBADrUL131 particles. The levels of gB, pp28 and pp65 were similar in the two virion preparations.
There is precedent in EBV for production of viruses with different relative amounts of a 01 complex: particles produced by B cells are deficient for gH/gL/gp42 (18). However, other factors may be involved. Perhaps a constituent of the complex that was not assayed is altered. Alternatively, the ratio of the gH complex to one or more additional virion glycoprotein complexes might modify fusion activity. Finally, it may be that an unidentified cell protein, supplied to the virions when they are produced within epithelial cells or fibroblasts, might alter the complex.
Are there physiological consequences to the two modes of entry? epiBADrUL131 and fibroBADrUL131 induced markedly different cellular transcriptional responses after infection of ARPE-19 cells. Assuming that the difference is indeed due to virions or virions plus specifically associated cellular factors, the microarray experiment demonstrates a strikingly different transcriptional response to infection. Endocytosis is intimately involved in the regulation of signaling by cell surface molecules. As a consequence, a virus might modulate cell signaling, and the cellular transcriptome, differently if it enters by fusion at the plasma membrane versus endocytosis. The differences in cell signaling likely have physiological consequences that are not detected in cultured cells, such as effects on virus spread, immune evasion, or virulence.
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a) passaging two or more strains or isolates of CMV having a gene encoding a functional pUL131 protein in a fibroblast,
b) amplifying the two or more strains or isolates of CMV in an epithelial cell, thereby producing cell type-conditioned CMVs; and
c) producing a population of live attenuated, inactivated, or killed CMVs from the cell type-conditioned CMVs, thereby producing the immunogenic composition.
2. The method of claim 1, wherein the two or more strains or isolates of CMV are human CMV strains or isolates.
3. The method of claim 1, comprising amplifying the two or more strains or isolates of CMV in two or more different epithelial cells and combining the cell type-conditioned CMVs from the two or more different epithelial cells.
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GenBank Accession No. AL713743, "Homo sapiens mRNA; cDNA DKFZp761G0122 (from clone DKFZp761G0122)," Mar. 20, 2002; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. AW444553, "The sequence contained on oligo-dT track that was present in the oligonucleotide that was used to rpime the synthesis of first strand cDNA and therefore this may represent a bonafide poly A tail," Feb. 15, 2000; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. AW856073, "A mini-library was made by cloning products derived from ORESTES PCR (U.S. Letters Patent application No. 196,716-Ludwign Institute for Cancer Research) profiles into the pUC 18 vector. Reverse transcription of tissue mRNA and cDNA amplification were performed under low stringency conditions," May 19, 2000; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. AW856073, GenBank gi: 7951766, Lib. Name: CT0286, May 19, 2000; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. AY186194, "Rhesus cytomegalovirus strain 68-1, complete genome," Jun. 4, 2003; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-97.
GenBank Accession No. AY446894, "Human herpesvirus 5 strain Merlin, complete genome," Aug. 13, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-95.
GenBank Accession No. BC011595, "Homo sapiens glycoprotein (transmembrane) nmb, mRNA (cDNA clone Image:3345861), complete cds," Sep. 16, 2003; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. BC015929, "Homo sapiens nuclear receptor subfamily 1, group D, member 2, mRNA (cDNA clone Image:3912370), partial cds," Jan. 2, 2004; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. BC018597, "Homo sapiens, clone Image:3869276, mRNA," Dec. 3, 2001; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. BC039151, "Homo sapiens chromosome 20 open reading frame 119, mRNA (cDNA clone Image:4745538), with apparent retained intron," Nov. 17, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. BC043212, "Homo sapiens cDNA clone Image:5295205, with apparent retained intron," Sep. 16, 2003; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. BC048263, "Homo sapiens hypothetical protein LOC146909, mRNA (cDNA clone Image:4418755), partial cds," Sep. 30, 2003; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. BC071797, "Homo sapiens cDNA clone Image: 4618441, Warning: chimeric clone," Aug. 4, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. BF514513, "The sequence contained an oligo-dT track that was present in the oligonucleotide that was used to prime the synthesis of first strand cDNA and therefore this may represent a bonafide poly A tail," Dec. 7, 2000; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. BG001037, "A mini-library was made by cloning products derived from ORESTES PCR (U.S. Letters Patent application No. 196,716-18 vector. Reverse transcription of tissue mRNA and cDNA amplification were performed under low stringency conditions," Jan. 24, 2001; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. BK000394, "TPA-inf: Human herpesvirus 5 strain AD169, complete genome," Sep. 5, 2006; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-92.
GenBank Accession No. BU943730, "Double-stranded cDNA was prepared from a pool of 40 cell line polyA+RNAs," Oct. 17, 2002; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. BX104999, "1st strand cDNA was primed with a Pac I-oligo(dT) primer," Jan. 22, 2003; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. BX360933, "1st strand cDNA was primed with a NotI-oligo(dT) primer. Five prime end enriched, double-strand cDNA was digested with Not I and cloned into the Not I and EcoR V sites of the pCMVSPORT 6 vector. Library was normalized," May 5, 2003; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. CR594200, "full-length cDNA clone CS0DF031yH08 of Fetal brain of Homo sapiens (human) ," Jul. 21, 2004; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. CR598364, "full-length cDNA clone CS0CAP007YJ17 of Thymus of Homo sapiens (human) ," Jul. 21, 2004; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. CR622110, "full-length cDNA clone CS0DC025YP03 of Neuroblastoma Cot 25-normalized of Homo sapiens (human) ," Jul. 21, 2004; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. DB318210, "NEDO human cDNA project (New Energy and Industrial Technology Developmental Organization, Japan); cDNA library construction: Helix Research Institute (HRI); 5′-end one pass sequencing: HRI, Research Association for Biotechnology (RAB) and Biotechnology Center, National Institute of Technology and Evaluation; 3′-end one pass sequencing; RAB," Dec. 10, 2005; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. DB318210, "NEDO human cDNA project (New Energy and Industrial Technology Developmental Organization, Japan); cDNA library construction: Helix Research Institute (HRI); 5'-end one pass sequencing: HRI, Research Association for Biotechnology (RAB) and Biotechnology Center, National Institute of Technology and Evaluation; 3'-end one pass sequencing; RAB," Dec. 10, 2005; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. DB527271, "The full length cDNA libraries were prepared and sequenced using the Riken full length cDNA techniques in Genome Science Laboratory and Genome Exploration Research Group Genomic Sciences Center (GSC) in Riken. These sequences are contributed to the international ORFeome Collaboration. 3′-EST sequences are presented as anti-sense strand," Apr. 17, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. DB527271, "The full length cDNA libraries were prepared and sequenced using the Riken full length cDNA techniques in Genome Science Laboratory and Genome Exploration Research Group Genomic Sciences Center (GSC) in Riken. These sequences are contributed to the international ORFeome Collaboration. 3'-EST sequences are presented as anti-sense strand," Apr. 17, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. DQ205516, "Natronorubrum aibiense strain 7-3 16S ribosomal RNA gene, partial sequence," Jul. 10, 2006; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. HSU16307, "Homo sapiens glioma pathogenesis-related protein (GliPR) mRNA, complete cds," Oct. 23, 2002; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. HUMYT69G03, "Homo sapiens full length insert cDNA clone YT69G03," Aug. 29, 1998; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. L08436, "Human autonomously replicating sequence (ARS) mRNA," Nov. 8, 1993; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-1.
GenBank Accession No. NM 000641, "Homo sapiens interleukin 11 (IL11), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM 014351, "Homo sapiens sulfotransferase family 4A, member 1 (SULT4A1), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-000189, "Homo sapiens hexokinase 2 (HK2), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-000190, "Homo sapiens hydroxymethylbilane synthase (HMBS), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-000201, "Homo sapiens intercellular adhesion molecule 1 (CD54), human rhinovirus receptor (ICAM1), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-000212, "Homo sapiens integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) (ITGB3), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-000322, "Homo sapiens peripherin 2 (retinal degeneration, slow) (PRPH2), mRNA," Sep. 17, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-000362, "Homo sapiens TIMP metallopeptidase inhibitor 3 (Sorsby fundus dystrophy, pseudoinflammatory) (TIMP3), mRNA," Sep. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-8.
GenBank Accession No. NM-000364, "Homo sapiens troponin T type 2 (cardiac) (TNNT2), transcript variant 1, mRNA," Oct. 7, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-000372, "Homo sapiens tyrosinase (oculocutaneous albinism IA) (TYR), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-000499, "Homo sapiens cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), mRNA," Oct. 7, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-000640, "Homo sapiens interleukin 13 receptor, alpha 2 (IL13RA2), mRNA," Sep. 17, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-000693, "Homo sapiens aldehyde dehydrogenase 1 family, member A3 (ALDH1A3), mRNA," Jul. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-000782, "Homo sapiens cytochrome P450, family 24, subfamily A, polypeptide 1 (CYP24A1), nuclear gene encoding mitochondrial protein, mRNA," Sep. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-000800, "Homo sapiens fibroblast growth factor 1 (acidic) (FGF1), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-000808, "Homo sapiens gamma-aminobutyric acid (GABA), A receptor, alpha 3 (GABRA3), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-000916, "Homo sapiens oxytocin receptor (OXTR), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-000970, "Homo sapiens ribosomal protein L6 (RPL6), transcript variant 2, mRNA," Sep. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-001002926, "Homo sapiens TWIST neighbor (TWISTNB), nRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-001003683, "Homo sapiens phosphodiesterase 1A, calmodulin-dependent (PDE1A), transcript variant 2, mRNA," Sep. 17, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-001003940, "Homo sapiens Bc12 modifying factor (BMF), transcript variant 1, mRNA," Sep. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-001004301, "Homo sapiens zinc finger protein 813 (ZNF813), mRNA," Jun. 27, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-001009954, "Homo sapiens FLJ20105 protein (FLJ20105), transcript variant 2, mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-001010911, "Homo sapiens chromosome 10 open reading frame 114 (C10orf114), mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-001018084, "Homo sapiens solute carrier family 26, member 10 (SLC26A10), transcript variant 1, mRNA," Sep. 24, 2005; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-001033086, "Homo sapiens chromosome 20 open reading frame 133 (C20orf133), transcript variant 1, mRNA," Sep. 24, 2005; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-001034, "Homo sapiens ribonucleotide reductase M2 polypeptide (RRM2), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-001037442, "Homo sapiens Run and FYVE domain containing 3 (RUFY3), transcript variant 1, mRNA," Jul. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-001039580, "Homo sapiens microtubule-associated protein 9 (MAP9), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-001043, "Homo sapiens solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2 (SLC6A2), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-001165, "Homo sapiens baculoviral IAP repeat-containing 3 (BIRC3), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-001511, "Homo sapiens chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) (CXCL1), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-001548, "Homo sapiens interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), transcript variant 2, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-001624, "Homo sapiens absent in melanoma 1 (AIM1), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-001673, "Homo sapiens asparagine synthetase (ASNS), transcript variant 2, mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-001901, "Homo sapiens connective tissue growth factor (CTGF), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-001902, "Homo sapiens cystathionase (cystathionase gamma-lyase) (CTH), transcript variant 1, mRNA," Sep. 17, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-001946, "Homo sapiens dual specificity phosphatase 6 (DUSP6), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-002053, "Homo sapiens guanylate binding protein 1, interferon-inducible, 67kDa (GBP1), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-002104, "Homo sapiens granzyme K (granzyme 3; tryptase II) (GZMK), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-002167, "Homo sapiens inhibitor of DNA binding 3, dominant negative helix-loop-helix protein (ID3), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-002201, "Homo sapiens interferon stimulated exonuclease gene 20kDa (ISG20), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-002214, "Homo sapiens integrin, beta 8 (ITGB8), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-7.
GenBank Accession No. NM-002234, "Homo sapiens potassium voltage-gated channel, shaker-related subfamily, member 5 (KCNA5), mRNA," Sep. 17, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-002310, "Homo sapiens leukemia inhibitory factor receptor alpha (LIFR), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-8.
GenBank Accession No. NM-002526, "Homo sapiens 5′-nucleotidase, ecto (CD73) (NT5E), mRNA," Sep. 26, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-002609, "Homo sapiens platelet-derived growth factor receptor, beta polypeptide (PDGFRB), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-7.
GenBank Accession No. NM-002658, "Homo sapiens plasminogen activator, urokinase (PLAU), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-002670, "Homo sapiens plastin 1 (I isoform) (PLS1), mRNA," Nov. 17, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-002837, "Homo sapiens protein tyrosine phosphatase, receptor type, B (PTPRB), transcript variant 2, mRNA," Oct. 7, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-9.
GenBank Accession No. NM-002849, "Homo sapiens protein tyrosine phosphatase, receptor type, R (PTPRR), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-002852, "Homo sapiens pentraxin-related gene, rapidly induced by IL-1 beta (PTX3), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-002930, "Homo sapiens Ras-like without CAAX 2 (RIT2), mRNA," Sep. 29, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-002982, "Homo sapiens chemokine (C-C motif) ligand 2 (CCL2), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-003414, "Homo sapiens zinc finger protein 267 (ZNF267), transcript variant 498723, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-003425, "Homo sapiens zinc finger protein 45 (ZNF45), mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-003483, "Homo sapiens high mobility group AT-hook 2 (HMGA2), transcript variant 1, mRNA," Sep. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-003558, "Homo sapiens phosphatidylinositol-4-phosphate 5-kinase, type I, beta (PIP5KIB), transcript variant 2, mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-003706, "Homo sapiens phospholipase A2, group IVC (cytosolic, calcium-independent) (PLA2G4C), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-003786, "Homo sapiens ATP-binding cassette, sub-family C (CFTR/MRP), member 3 (ABCC3), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-8.
GenBank Accession No. NM-003841, "Homo sapiens tumor necrosis factor receptor superfamily, member 10c, decoy without an intracellular domain (TNFRSF10C), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-003862, "Homo sapiens fibroblast growth factor 18 (FGF18), mRNA," Sep. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-003897, "Homo sapiens immediate early response 3 (IER3), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-004170, "Homo sapiens solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1 (SLC1A1), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-004185, "Homo sapiens wingless-type MMTV integration site family, member 2B (WNT2B), transcript variant VNT-2B1, mRNA," Sep. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-004233, "Homo sapiens CD83 molecule (CD83), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-004294, "Homo sapiens mitochondrial translational release factor 1 (MTRF1), nuclear gene encoding mitochondrial protein, mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-004318, "Homo sapiens aspartate beta-hydroxylase (ASPH), transcript variant 1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-004334, "Homo sapiens bone marrow stromal cell antigen 1 (BST1), mRNA," Sep. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-004464, "Homo sapiens fibroblast growth factor 5 (FGF5), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-004466, "Homo sapiens glypican 5 (GPC5), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-004556, "Homo sapiens nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon (NFKBIE), mRNA," Sep. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-004843, "Homo sapiens interleukin 27 receptor, alpha (IL27RA), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-005031, "Homo sapiens FXYD domain containing ion transport regulator 1 (phospholemman) (FXYD1), transcript variant a, mRNA," Sep. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-005039, "Homo sapiens proline-rich protein BstNI subfamily 1 (PRB1), transcript variant 1, mRNA," Jul. 29, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-005185, "Homo sapiens calmodulin-like 3 (CALML3), mRNA," Sep. 17, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-005261, "Homo sapiensGTP binding protein overexpressed in skeletal muscle (GEM), transcript variant 1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-005341, "Homo sapiens zinc finger and BTB domain containing 48 (ZBTB48), mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-005345, "Homo sapiens heat shock 70kDa protein 1A (HSPA1A), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-005347, "Homo sapiens heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) (HSPA5), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-005444, "Homo sapiens RCD1 required for cell differentiationl homolog (S. pombe) (RQCD1), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-005515, "Homo sapiens motor neuron and pancreas homeobox 1 (MNX1), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-005527, "Homo sapiens heat shock 70kDa protein 1-like (HSPA1L), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-005923, "Homo sapiens mitogen-activated protein kinase kinase kinase 5 (MAP3K5), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-7.
GenBank Accession No. NM-006187, "Homo sapiens 2′ -5′ -oligoadenylate synthetase 3, 1001cDa (OAS3), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-006393, "Homo sapiens nebulette (NEBL), transcript variant 1, mRNA," Sep. 17, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-7.
GenBank Accession No. NM-006417, "Homo sapiens interferon-induced protein 44 (IFI44), mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-006434, "Homo sapiens sorbin and SH3 domain containing 1 (SORBS1), transcript variant 1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-7.
GenBank Accession No. NM-006509, "Homo sapiens v-rel reticuloendotheliosis viral oncogene homlog B, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3 (avian) (RELB), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-006516, "Homo sapiens solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1), mRNA," Sep. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-006547, "Homo sapiens insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-006611, "Homo sapiens killer cell lectin-like receptor subfamily A, member 1 (KLRA1), mRNA," Jul. 29, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-006650, "Homo sapiens complexin 2 (CPLX2), transcript variant 1, mRNA," Sep. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-006793, "Homo sapiens peroxiredoxin 3 (PRDX3), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA," Sep. 17, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-006851, "Homo sapiens GLI pathogenesis-related 1 (glioma) (GLIPR1), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-006933, "Homo sapiens solute carrier family 5 (inositol transporters), member 3 (SLC5A3), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-007107, "Homo sapiens signal sequence receptor, gamma (translocon-associated protein gamma) (SSR3), mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-007211, "Homo sapiens Ras association (Ra1GDS/AF-6) domain family 8 (RASSF8), mRNA," Sep. 29, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-007282, "Homo sapiens ring finger protein 13 (RNF13), transcript variant 1, mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-007314, "Homo sapiens v-abl Abelson murein leukemia viral oncogene homolog 2 (arg, Abelson-related gene) (ABL2), transcript variant b, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-8.
GenBank Accession No. NM-012329, "Homo sapiens monocyte to macrophage differentiation-associated (MMD), mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-012377, "Homo sapiens olfactory receptor, family 7, subfamily C, member 2 (OR7C2), mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-012419, "Homo sapiens regulator of G-protein signaling 17 (RGS17), mRNA," Aug. 24, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-013261, "Homo sapiens peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PPARGC1A), mRNA," Oct. 7, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-7.
GenBank Accession No. NM-013989, "Homo sapiens deiodinase, iodothyronine, type II (DIO2), transcript variant 1, mRNA," Sep. 24, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-014314, "Homo sapiens Dead (Asp-Glu-Ala-Asp) box polypeptide 58 (DDX58), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-7.
GenBank Accession No. NM-014331, "Homo sapiens solute carrier family 7,"cationic amino acid transporter, y+ system) member 11 (SLC7A11), mRNA, Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-014632, "Homo sapiens microtubule associated monoxygenase, calponin and LIM domain containing 2 (MICAL2), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-014729, "Homo sapiens thymocyte selection-associated high mobility group box (TOX), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-015009, "Homo sapiens PDZ domain containing Ring finger 3 (PDZRN3), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-015074, "Homo sapiens kinesin family member 1B (KIF1B), transcript variant 1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-10.
GenBank Accession No. NM-015359, "Homo sapiens solute carrier family 39 (zinc transporter), member 14 (SLC39A14), mRNA," Sep. 29, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer/fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-016125, "Homo sapiens PTD016 protein (LOC51136), mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-016239, "Homo sapiens myosin XVA (MY015A), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-12.
GenBank Accession No. NM-016354, "Homo sapiens solute carrier organic anion transporter family, member 4A1 (SLC04A1), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-016613, "Homo sapiens chromosome 4 open reading frame (C4orf18), transcript variant 2, mRNA," Sep. 29, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-016831, "Homo sapiens period homolog 3 (Drosphila) (PER3), mRNA," Sep. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-7.
GenBank Accession No. NM-017577, "Homo sapiens GRAM domain containing 1C (GRAMD1C), mRNA," Sep. 29, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-017600, "Homo sapiens golgi autoantigen, golgin subfamily a, 2-like 1 (GOLGA2L1), mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-017638, "Homo sapiens mediator complex subunit 18 (MED18), mRNA," Aug. 4, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-017644, "Homo sapiens kelch-like 24 (Drosophila) (KLHL24), mRNA," Aug. 4, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-018027, "Homo sapiens FERM domain containing 4A (FRMD4A), mRNA," Jun. 23, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-018284, "Homo sapiens guanylate binding protein 3 (GBP3), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-018371, "Homo sapiens chondroitin betal,4 N-acetylgalactosaminyltransferase (ChGn), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-018372, "Homo sapiens chromosome 1 open reading frame 103 (Clorf103), transcript variant 1, mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-018664, "Homo sapiens Jun dimerization protein p21SNFT (SNFT), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. NM-018836, "Homo sapiens adherens junction associated protein 1 (AJAP1), transcript variant 1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-019555, "Homo sapiens Rho guanine nucleotide exchange factor (GEF) 3 (ARHGEF3), mRNA," Sep. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-019891, "Homo sapiens ERO1-like beta (S. cerevisiae) (ERO1LB), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-020359, "Homo sapiens phospholipid scramblase 2 (PLSCR2), mRNA," Nov. 17, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-020436, "Homo sapiens sal-like 4 (Drosophila) (SALL4), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-020683, "Homo sapiens adenosine A3 receptor (ADORA3), transcript variant 1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-020731, "Homo sapiens aryl-hydrocarbon receptor repressor (AHRR), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-020799, "Homo sapiens STAM binding protein-like 1 (STAMBPL1), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.ov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-020904, "Homo sapiens pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 4 (PLEKHA4), mRNA," Nov. 17, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-020943, "Homo sapiens KIAA1604 protein (KIAA1604), mRNA," Jul. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-020988, "Homo sapiens guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O (GNA01), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-021101, "Homo sapiens claudin 1 (CLDN1), mRNA" Sep. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-021377, "Mus musculus VPS10 domain receptor protein SORCS 1 (Sores 1), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-021727, "Homo sapiens fatty acid desaturase 3 (FADS3), mRNA," Nov. 17, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-021813, "Homo sapiens BTB and CNC homology 1, basic leucine zipper transcription factor 2 (BACH2), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-021990, "Homo sapiens gamma-aminobutyric acid (GABA) A receptor, epsilon (GABRE), transcript variant 4, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-022044, "Homo sapiens stromal cell-derived factor 2-like 1 (SDF2L1), mRNA," Jun. 27, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. NM-022047, "Homo sapiens differentially expressed in FDCP 6 homolog (mouse) (DEF6), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-022097, "Homo sapiens calcineurin B homologous protein 2 (CHP2), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-022115, "Homo sapiens PR domain containing 15 (PRDM15), transcript variant 1, mRNA," Jun. 27, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-022160, "Homo sapiens DMRT-like family A1 (DMRTA1), mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-022842, "Homo sapiens CUB domain containing protein 1 (CDCP1), transcript variant 1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-023070, "Homo sapiens zinc finger protein 643 (ZNF643), mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-024050, "Homo sapiens chromosome 19 open reading frame 58 (C19orf58), mRNA," Jul. 1, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. NM-024050, "Homo sapiens chromosome 19 open reading frame 58 (C19orf58), mRNA," Jul. 1, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. NM-024525, "Homo sapiens tetratricopeptide repeat domain 13 (TTC13), mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-024861, "Homo sapiens chromosome 2 open reading frame 54 (C2orf54), transcript variant 2, mRNA," Jul. 1, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-025169, "Homo sapiens zinc finger protein 167 (ZNF167), transcript variant 2, mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-031217, "Homo sapiens kinesin family member 18A (KIF18A), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-031466, "Homo sapiens NIK and IKK(beta) binding protein (NIBP), mRNA," Sep. 29, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-031938, "Homo sapiens beta-carotene dioxygenase 2 (BCD02), transcript variant 1, mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-032188, "Homo sapiens MYST histone acetyltransferase 1 (MYST1), transcript variant 1, mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-032228, "Homo sapiens male sterility domain containing 2 (MLSTD2), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-032266, "Homo sapiens chromosome 2 open reading frame 16 (C2orf16), mRNA," Jul. 24, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-032434, "Homo sapiens zinc finger protein 512 (ZNF512), mRNA," Jun. 22, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-032523, "Homo sapiens oxysterol binding protein-like 6 (OSBPL6), transcript variant 1, mRNA," Nov. 17, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-032778, "Homo sapiens MYC induced nuclear antigen (MINA), transcript variant 3, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-032866, "Homo sapiens cingulin-like 1 (CGNL1), mRNA," Jun. 27, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-033036, "Homo sapiens galactose-3-0-sulfotransferase 3 (GAL3ST3), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-033066, "Homo sapiens membrane protein, palmitoylated 4 (MAGUK p55 subfamily member 4) (MPP4) mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-033160, "Homo sapiens zinc finger protein 658 (ZNF658), mRNA," Aug. 18, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-033260, "Homo sapiens forkhead boX Q1 (FOXQ1), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.nebi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-052875, "Homo sapiens vacuolar protein sorting 26 homolog B (S. pombe) (VPS26B), mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-052892, "Homo sapiens polycystic kidney disease 1-like 2 (PKD1L2), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-8.
GenBank Accession No. NM-053064, "Homo sapiens guanine nucleotide binding protein (G protein), gamma 2 (GNG2), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-058179, "Homo sapiens phosphoserine aminotransferase 1 (PSAT1), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.nebi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-058188, "Homo sapiens chromosome 21 open reading frame 67 (C21orf67), mRNA," Dec. 13, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. NM-080927, "Homo sapiens discoidin, CUB and LCCL domain containing 2 (DCBLD2), mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-133492, "Homo sapiens N-acylsphingosine amidohydrolase (alkaline ceramidase) 3 (ASAH3), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-138440, "Homo sapiens vasorin (VASN), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-138467, "Homo sapiens tRNA-yW synthesizing protein 3 homolog (S. Cerevisiae) (TYW3), mRNA," Jul. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-139173, "Homo sapiens Na+/H+ exchanger domain containing 1 (NHEDC1), transcript variant 1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-139314, "Homo sapiens angiopoietin-like 4 (ANGPTL4), transcript variant 1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-144620, "Homo sapiens leucine rich repeat containing 39 (LRRC39), mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-144633, "Homo sapiens potassium voltage-gated channel, subfamily H (eag-related), member 8 (KCNH8), mRNA," Jan. 26, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-145023, "Homo sapiens coiled-coil domain containing 7 (CCDC7), transcript variant 1, mRNA," Jul. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-145051, "Homo sapiens ring finger protein 183 (RNF183), mRNA," Jul. 24, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-145306, "Homo sapiens chromosome 10 open reading frame 35 (C10orf35), mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-145867, "Homo sapiens leukotriene C4 synthase (LTC4S), mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-152377, "Homo sapiens chromosome 1 open reading frame 87 (Clorf87), mRNA," Nov. 17, 2006; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-152408, "Homo sapiens chromosome 5 open reading frame 37 (C5orf37), transcript variant 2, mRNA," Jul. 5, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-152525, "Homo sapiens amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 11 (ALS2CR11), mRNA," Jun. 27, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-152649, "Homo sapiens mixed lineage kinase domain-like (MLKL), mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-153689, "Homo sapiens hypothetical protein FLJ38973 (FLJ38973), mRNA," Jun. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-172345, "Homo sapiens sperm associated antigen 9 (SPAG9), transcript variant 2, mRNA," Mar. 20, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-173039, "Homo sapiens aquaporin 11 (AQP11), mRNA," Nov. 17, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. NM-173082, "Homo sapiens SNF2 histone linker PHD Ring helicase (SHPRH), transcript variant 2, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-7.
GenBank Accession No. NM-173550; "Homo sapiens chromosome 9 open reading frame 93 (C9orf93), mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-175868, "Homo sapiens melanoma antigen family A, 6 (MAGEA6), transcript variant 2, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-180989, "Homo sapiens G protein-coupled receptor 180 (GPR180), mRNA," Sep. 26, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-181795, "Homo sapiens protein kinase (cAMP-dependent, catalytic) inhibitor beta (PKIB), transcript variant 1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-182728, "Homo sapiens solute carrier family 7 (cationic amino acid transporter, y+ system), member 8 (SLC7A8), transcript variant 2, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-182751, "Homo sapiens minichromosome maintenance complex component 10 (MCM10), transcript variant 1, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-182920, "Homo sapiens ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-8.
GenBank Accession No. NM-183040, "Homo sapiens dystrobrevin binding protein 1 (DTNBP1), transcript variant 2, mRNA," Sep. 30, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-194303, "Homo sapiens chromosome 10 open reading frame 39 (C10orf39), mRNA," Nov. 17, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-198353, "Homo sapiens potassium channel tetramerisation domain containing 8 (KCTD8), mRNA," Jun. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-198404, "Homo sapiens potassium channel tetramerisation domain containing 4 (KCTD4), mRNA," Jul. 1, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NM-198569, "Homo sapiens G protein-coupled receptor 136 (GPR126), transcript variant b1, mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-6.
GenBank Accession No. NM-198833, "Homo sapiens serpin peptidase inhibitor, clade B (ovalbumin), member 8 (SERPINB8), transcript variant 2, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-198951, "Homo sapiens transglutaminase 2 (C polypeptide, protein-glutamine-gamma-glutamyltransferase) (TGM2), transcript variant 2, mRNA," Sep. 25, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NM-203434, "Homo sapiens immediate early response 5-like (IER5L), mRNA," Jul. 1, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. NM-205849, "Homo sapiens family with sequence similarity 9, member B (FAM9B), mRNA," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-3.
GenBank Accession No. NR-001279, "Homo sapiens cystatin pseudogene (LOC164380) on chromosome 20," Jun. 27, 2007; Retrieved from the Internet on Aug. 11, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. NR-002186, "Homo sapiens hypothetical protein DKFZp58611420 (DKFZp58611420) on chromosome 7," Jun. 27, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
GenBank Accession No. NR-002802, "Homo sapiens trophoblast-derived noncoding RNA (TncRNA) on chromosome 11," Jun. 27, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-5.
GenBank Accession No. NR-002819, "Homo sapiens metastasis associated lung adenocarcinomatranscript 1 (non-coding RNA) (MALAT1) on chromosome 11," Sep. 3, 2007; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-4.
GenBank Accession No. XM-210365, "Predicted: Homo sapiens similiar to ribosomal protein L24-like (LOC284288), mRNA," Aug. 29, 2006; Retrieved from the Internet on Aug. 10, 2010: http://www.ncbi.nlm.nih.gov/sviewer/viewer.fcgi?val . . . pp. 1-2.
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