Chapter 16 : Gene Therapy and Viruses

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Gene therapy is an emerging medical approach which seeks to apply molecular techniques to attack diseases at the fundamental level of the genes. The first techniques which were developed for genetic manipulation of mammalian cells involved direct introduction of genes in the forms of expression plasmids by physical methods. However, other gene therapy applications require stable persistence of the transferred gene in the target cells, so that the gene will be retained with each cell division and inherited by all progeny cells. The viruses which have been adapted and most widely studied for gene transfer include retroviruses, adenovirus (Ad), adeno-associated virus (AAV), herpesviruses, and, most recently, lentiviruses. Importantly, lentiviral vectors tolerate complex genetic elements better than retroviral vectors, possibly aided by the Rev/Rev response element-mediated mechanism for nuclear-to-cytoplasmic export of HIV-1 transcripts. Complement fixation (CF) appeared to be an attractive target for gene therapy, and extensive preclinical studies of the safety and toxicity of an AAV-CF transmembrane regulator (CFTR) vector were performed by delivery of vector particles directly to the lungs in rabbits and nonhuman primates. Importantly, sperm is generally negative for vector sequences, which diminishes the likelihood of modifying germ line cells. The use of viruses with improved initial intratumoral distribution and carrying genes that both overcome innate immune responses and promote an intra-cellular proapoptotic state should improve the potency of herpes simplex virus (HSV) cancer gene therapy vectors without compromising safety.

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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Image of FIGURE 1

Diagrams of typical simple retrovirus and retroviral vector. (Top) Retroviruses have LTR at each end, the psi encapsidation sequences (ψ), and regions encoding the Gag, Pol, and Env polyproteins. Splice donor (D) and acceptor (A) sites allow some of the vector transcripts to be spliced to generate subgenomic RNA for translation of the gene. (Bottom) Retrovirus vectors contain the LTR and ψ regions of the retrovirus with the exogenous gene(s) sequences cloned between.

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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Image of FIGURE 2

Retroviral vector packaging constructs. First-generation packaging constructs had the packaging region deleted to prevent packaging of the transcripts encoding the viral proteins. Second-generation packaging constructs were further altered to minimize the potential for generation of RCR through recombination with sequences in the vector. The 5′ end of the 5′ LTR was deleted and the entire 3′ LTR was replaced with an exogenous polyadenylation signal. Third-generation packaging systems had the open reading frames for Gag-Pol and Env placed on separate plasmids to further minimize the potential for recombination to generate RCR. SV40, simian virus 40.

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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Image of FIGURE 3

Production of lentiviral vectors from stable packaging cell lines and by transient transfection. (A) Stable packaging cell lines can be developed by stable transfection of a cell line to express the Gag, Pol, and Env proteins. Subsequent transfection of the plasmid encoding a retrovirus vector allows the vector genomic RNA to be packaged by the retroviral proteins. (B) Retroviral vectors can be produced by transient transfection of a susceptible cell line, such as 293T, with all of the plasmids encoding the vector, the virion proteins, and an envelope protein.

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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Image of FIGURE 4

Life cycle of a retroviral vector. Retroviral vectors are constructed as plasmids to contain the essential retroviral elements (LTR and psi region) and the transgene and other expression regulatory elements. The plasmid is transfected into a cell for packaging, with either stable or transient coexpression of the necessary retroviral proteins in The vector transcripts serve as the virion genome and are packaged into virions and released from the cell. The vector virions can then be used to transduce a target cell, where the vector RNA genome is reverse transcribed into double-stranded (ds) DNA and integrated into the target cell chromosomes as a provirus. The proviral sequences can be transcribed into mRNA that is translated to make the transgene product. ss, single stranded.

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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Image of FIGURE 5

Potential mechanisms of insertional oncogenesis by retroviral vectors. Retroviral vectors integrate into the target cell chromosomes and may affect the expression of nearby cellular genes. Gene disruption may occur if the retroviral vector integrates within the cellular gene; tumor suppressor genes may be inactivated by this process. Transcriptional read-through may occur from integrated vector proviruses into downstream cellular genes in the same orientation; inappropriate expression of cellular oncogenes may occur by this process. Enhancement of expression of cellular genes may occur if strong enhancer elements of the vectors activate expression from the promoters of nearby cellular genes, independently of the relative orientation of the vector (depicted as an upside-down vector in reverse transcriptional orientation relative to the cellular gene). (Figure kindly provided by Erin Weber, U.S.C. Keck School of Medicine.)

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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Image of FIGURE 6

SIN lentiviral vectors. The SIN vector plasmid contains deletion of the enhancer and promoter of the 3′ LTR, which are not needed for expression from the plasmid in a packaging cell line. Following packaging of the vector and reverse transcription of the vector genome in a target cell, the 3′ LTR with the deletions of the enhancer and promoter is used as the template for the analogous region of the 5′ LTR, leading to a provirus with both LTR being transcriptionally inactive. Expression of the exogenous gene will then be driven from the internal promoter (Int Prom), which may be lineage specific or have other useful expression patterns. CMV, cytomegalovirus.

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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Image of FIGURE 7

Maps of the genomes of wild-type AAV serotype 2 and AAV vector. (A) The AAV serotype 2 genome is 4,681 nucleotides long and is shown on a linear scale of 100 map units. The open boxes show the ITR. The closed circles show the transcription promoters at 5, 19, and 40 map units. The gene is transcribed from both the p5 and p19 promoters. The gene is transcribed from the p40 promoter. (B) Schematic diagram of an AAV vector. The entire AAV coding sequence, including the and genes, is removed, leaving only the ITR that are required for the origin of replication and for encapsidation. The gene of interest, with appropriate regulatory sequences such as transcription promoter (p) and polyadenylation site (A), is inserted between the ITR.

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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Image of FIGURE 8

AAV life cycle. In the absence of helper virus, AAV enters a latent phase. In cultured cells in vitro, this latent phase leads to chromosomal integration of the AAV genome (see text). In vivo, such as in humans, latency may involve persistence of the AAV genome as an episome. The productive phase occurs if helper virus is present and coinfects the host cells. If latently infected cells in vitro are later infected with helper virus, the AAV DNA can be rescued from the host cell genome by replication. This rescue and amplification of AAV from latently infected cells in vitro together form the basis for production of AAV vectors as discussed in the text.

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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Image of FIGURE 9

Generation of three major types of HSV vectors on the basis of the genes targeted for deletion. (A) Replication-competent vectors are generated by deletion of accessory genes to replicate in tumor cells preferentially over normal cells; (B) replication-defective vectors are generated by deletion of an essential gene(s) to block virus growth; (C) amplicon vectors are generated using plasmids bearing the HSV origin of DNA replication.

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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1. Aiuti, A.,, S. Slavin,, M. Aker,, F. Ficara,, S. Deola,, A. Mortellaro,, S. Morecki,, G. Andolfi,, A. Tabucchi,, F. Carlucci,, E. Marinello,, F. Cattaneo,, S. Vai,, P. Servida,, R. Miniero,, M. G. Roncarolo, and, C. Bordignon. 2002. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 296: 24102413.
2. Anderson, W. F.,, G. J. McGarrity, and, R. C. Moen. 1993. Report to the NIH Recombinant DNA Advisory Committee on murine replication-competent retrovirus (RCR) assays. Hum. Gene Ther. 4: 311321.
3. Bandyopadhyay, P. K.,, and H. M. Temin. 1984. Expression of complete chicken thymidine kinase gene inserted in a retrovirus vector. Mol. Cell Biol. 4: 749754.
4. Barouch, D. H.,, and G. J. Nabel. 2005. Adenovirus vector based vaccines for human immunodeficiency virus type 1. Hum. Gene Ther. 16: 149156.
5. Beck, S. E.,, L. A. Jones,, K. Chesnut,, S. Walsh,, T. Reynolds,, B. J. Carter,, F. B. Askin,, T. R. Flotte, and, W. B. Guggino. 1999. Repeated delivery of adeno-associated virus vectors to rabbit airway. J. Virol. 73: 94469455.
6. Berry, C.,, S. Hannenhalli,, J. Leipzig, and, F. D. Bushman. 2006. Selection of target sites for mobile DNA integration in the human genome. PLoS Comput. Biol. 2: e157.
7. Brantly, M. L.,, L. T. Spencer,, M. Humphries,, T. J. Conlon,, C. T. Spencer,, A. Poirier,, W. Garlington,, D. Baker,, S. Song,, K. I. Berns,, N. Muzyczka,, R. O. Snyder,, B. J. Byrne, and, T. R. Flotte. 2006. Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 α1-antitrypsin (AAT) vector in AAT-deficient adults. Hum. Gene Ther. 17: 11771186.
8. Bukrinsky, M. I.,, N. Sharova,, M. P. Dempsey,, T. L. Stanwick,, A. G. Bukrinskaya,, S. Haggerty, and, M. Stevenson. 1992. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc. Natl. Acad. Sci. USA 89: 65806584.
9. Carroll, R.,, J. T. Lin,, E. J. Dacquel,, J. D. Mosca,, D. S. Burke, and, D. C. St. Louis. 1994. A human immunodeficiency virus type 1 (HIV-1)-based retroviral vector system utilizing stable HIV-1 packaging cell lines. J. Virol. 68: 60476051.
10. Carter, B. J. 2005. Adeno-associated virus vectors in clinical trials. Hum. Gene Ther. 16: 541550.
11. Carter, B. J. 2006. Clinical development with adeno-associated virus vectors, p. 499–510. In J. R. Kerr,, S. F. Cotmore,, M. E. Bloom,, R. M. Linden, and, C. R. Parrish (ed.), Parvoviruses. Hodder Arnold, London, United Kingdom.
12. Carter, B. J.,, H. Burstein, and, R. W. Peluso. 2004. Adeno-associated virus and AAV vectors for gene delivery, p. 71–101. In N. S. Templeton (ed.), Gene Therapy: Therapeutic Mechanisms and Strategies, 2nd ed. Marcel Dekker, New York, NY.
13. Cavazzana-Calvo, M.,, S. Hacein-Bey,, G. de Saint Basile,, F. Gross,, E. Yvon,, P. Nusbaum,, F. Selz,, C. Hue,, S. Certain,, J. L. Casanova,, P. Bousso,, F. Le Deist, and, A. Fischer. 2000. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 288: 669672.
14. Chattopadhyay, M.,, D. Wolfe,, M. Mata,, S. Huang,, J. C. Glorioso, and, D. J. Fink. 2005. Long-term neuroprotection achieved with latency-associated promoter-driven herpes simplex virus gene transfer to the peripheral nervous system. Mol. Ther. 12: 307313.
15. Chirmule, N.,, W. Xiao,, A. Truneh,, M. Schnell,, J. V. Hughes,, P. Zoltich, and, J. M. Wilson. 2000. Humoral immunity to adeno-associated virus type 2 vectors following administration to murine and non-human primate muscle. J. Virol. 74: 24202425.
16. Conrad, C. K.,, S. S. Allen,, S. A. Afione,, T. C. Reynolds,, S. E. Beck,, M. Fee-Maki,, X. Barrazza-Ortiz,, R. Adams,, F. B. Askin,, B. J. Carter,, W. B. Guggino, and, T. R. Flotte. 1996. Safety of single-dose administration of an adeno-associated virus (AAV-CFTR) vector in the primate lung. Gene Ther. 3: 658668.
17. Costantini, L. C.,, D. R. Jacoby,, S. Wang,, C. Fraefel,, X. O. Breakefield, and, O. Isacson. 1999. Gene transfer to the nigrostriatal system by hybrid herpes simplex virus/adeno-associated virus amplicon vectors. Hum. Gene Ther. 10: 24812494.
18. Croen, K. D.,, J. M. Ostrove,, L. J. Dragovic,, J. E. Smialek, and, S. E. Straus. 1987. Latent herpes simplex virus in human trigeminal ganglia. Detection of an immediate early gene “anti-sense” transcript by in situ hybridization. N. Engl. J. Med. 317: 14271432.
19. Crystal, R. G.,, N. G. McElvaney,, M. A. Rosenfeld,, C. S. Chu,, A. Mastrangeli,, J. G. Hay,, S. L. Brody,, H. A. Jaffe,, N. T. T. Eissa, and, C. Danel. 1994. Administration of an adenovirus containing the human CFTR CDNA to the respiratory tract of individuals with cystic fibrosis. Nat. Genet. 8: 4251.
20. Curiel, D. T. 1999. Strategies to adapt adenoviral vectors for target delivery. Ann. N.Y. Acad. Sci. 886: 158171.
21. Delelis, O.,, A. Saib, and, P. Sonigo. 2003. Biphasic DNA synthesis in spumaviruses. J. Virol. 77: 81418161.
22. Detta, A.,, J. Harland,, I. Hanif,, S. M. Brown, and, G. Cruickshank. 2003. Proliferative activity and in vitro replication of HSV1716 in human metastatic brain tumours. J. Gene Med. 5: 681689.
23. Donahue, R. E.,, S. W. Kessler,, D. Bodine,, K. McDonagh,, C. Dunbar,, S. Goodman,, B. Agricola,, E. Byrne,, M. Raffeld,, R. Moen,, J. Bacher,, K. M. Zsebo, and, A. W. Nienhuis. 1992. Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer. J. Exp. Med. 176: 11251135.
24. Du, Y.,, S. E. Spence,, N. A. Jenkins, and, N. G. Copeland. 2005. Cooperating cancer-gene identification through oncogenic-retrovirus-induced insertional mutagenesis. Blood 106: 24982505.
25. Dull, T.,, R. Zufferey,, M. Kelly,, R. J. Mandel,, M. Nguyen,, D. Trono, and, L. Naldini. 1998. A third-generation lentivirus vector with a conditional packaging system. J. Virol. 72: 84638471.
26. Emi, N.,, T. Friedmann, and, J. K. Yee. 1991. Pseudotype formation of murine leukemia virus with the G protein of vesicular stomatitis virus. J. Virol. 65: 12021207.
27. Fallaux, F. J.,, A. Bout,, I. van der Velde,, D. J. van den Wollenberg,, K. M. Hehir,, J. Keegan,, C. Auger,, S. J. Cramer,, H. van Ormondt,, A. J. vander Eb,, D. Valerio, and, R. C. Hoeben. 1998. New helper cells and matched early region 1-deleted adenovirus vectors to prevent generation of replication-competent adenoviruses. Hum. Gene Ther. 9: 19091917.
28. Felgner, P. L. 1997. Nonviral strategies for gene therapy. Sci. Am. 276: 102106.
29. Feng, M.,, W. H. Jackson,, C. K. Goldman,, C. Rancourt,, M. Wang,, S. K. Dusing,, G. Siegal, and, D. T. Curiel. 1997. Stable in vivo gene transduction via a novel adenoviral/retroviral chimeric vector. Nat. Biotechnol. 15: 866870.
30. Fisher, K. J.,, W. M. Kelley,, J. F. Burda, and, J. M. Wilson. 1996. A novel adenovirus-adeno-associated virus hybrid vector displays efficient rescue and delivery of the AAV genome. Hum. Gene Ther. 7: 20792087.
31. Gallay, P.,, S. Swingler,, C. Aiken, and, D. Trono. 1995. HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator. Cell 80: 379388.
32. Ganly, I.,, D. S. Soutar, and, S. B. Kaye. 2000. Current role of gene therapy in head and neck cancer. Eur. J. Surg. Oncol. 26: 338343.
33. Gaspar, H. B.,, K. L. Parsley,, S. Howe,, D. King,, K. C. Gilmour,, J. Sinclair,, G. Brouns,, M. Schmidt,, C. Von Kalle,, T. Barington,, M. A. Jakobsen,, H. O. Christensen,, A. Al Ghonaium,, H. N. White,, J. L. Smith,, R. J. Levinsky,, R. R. Ali,, C. Kinnon, and, A. J. Thrasher. 2004. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector. Lancet 364: 21812187.
34. Gaspar, H. B.,, E. Bjorkegren,, K. Parsley,, K. C. Gilmour,, D. King,, J. Sinclair,, F. Zhang,, A. Giannakopoulos,, S. Adams,, L. D. Fairbanks,, J. Gaspar,, L. Henderson,, J. H. Xu-Bayford,, E. G. Davies,, P. A. Veys,, C. Kinnon, and, A. J. Thrasher. 2006. Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol. Ther. 14: 505513.
35. Geller, A.,, and X. Breakefield. 1988. A defective HSV-1 vector expresses Escherichia coli β-galactosidase in cultured peripheral neurons. Science 241: 16671669.
36. Geller, A.,, K. Keyomarsi,, J. Bryan, and, A. Pardee. 1990. An efficient deletion mutant packaging system for defective herpes simplex virus vectors: potential applications to human gene therapy and neuronal physiology. Proc. Natl. Acad. Sci. USA 87: 89508954.
37. Goss, J. R.,, C. F. Harley,, M. Mata,, M. E. O’Malley,, W. F. Goins,, X. Hu,, J. C. Glorioso, and, D. J. Fink. 2002. Herpes vector-mediated expression of proenkephalin reduces bone cancer pain. Ann. Neurol. 52: 662665.
38. Goss, J. R.,, M. Mata,, W. F. Goins,, H. H. Wu,, J. C. Glorioso, and, D. J. Fink. 2001. Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion. Gene Ther. 8: 551556.
39. Hacein-Bey-Abina, S.,, F. Le Deist,, F. Carlier,, C. Bouneaud,, C. Hue,, J. P. De Villartay,, A. J. Thrasher,, N. Wulffraat,, R. Sorensen,, S. Dupuis-Girod,, A. Fischer,, E. G. Davies,, W. Kuis,, L. Leiva, and, M. Cavazzana-Calvo. 2002. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N. Engl. J. Med. 346: 11851193.
40. Hacein-Bey-Abina, S.,, C. Von Kalle,, M. Schmidt,, M. P. McCormack,, N. Wulffraat,, P. Leboulch,, A. Lim,, C. S. Osborne,, R. Pawliuk,, E. Morillon,, R. Sorensen,, A. Forster,, P. Fraser,, J. L. Cohen,, G. de Saint Basile,, I. Alexander,, U. Wintergerst,, T. Frebourg,, A. Aurias,, D. Stoppa-Lyonnet,, S. Romana,, I. Radford-Weiss,, F. Gross,, F. Valensi,, E. Delabesse,, E. Macintyre,, F. Sigaux,, J. Soulier,, L. E. Leiva,, M. Wissler,, C. Prinz,, T. H. Rabbitts,, F. Le Deist,, A. Fischer, and, M. Cavazzana-Calvo. 2003. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302: 415419.
41. Hackett, N. R.,, and R. G. Crystal. 2004. Adenovirus vectors for gene therapy, p. 17–41. In N. S. Templeton (ed.), Gene Therapy, Therapeutic Mechanisms and Strategies, 2nd ed. Marcel Dekker, New York, NY.
42. Halbert, C.,, T. A. Standaert,, C. B. Wilson, and, A. D. Miller. 1998. Successful readministration of adeno-associated virus vectors to the mouse lung requires transient immunosuppression during the initial exposure. J. Virol. 72: 97959805.
43. Halbert, C. L.,, A. D. Miller,, A. McNamara,, J. Emerson,, R. L. Gibson,, B. Ramsey, and, M. L. Aitken. 2006. Prevalence of neutralizing antibodies against adeno-associated virus (AAV) types 2, 5, and 6 in cystic fibrosis and normal populations: implications for gene therapy using AAV vectors. Hum. Gene Ther. 17: 440447.
44. Hao, S.,, M. Mata,, J. C. Glorioso, and, D. J. Fink. 2007. Gene transfer to interfere with TNFalpha signaling in neuropathic pain. Gene Ther. 14: 10101016.
45. Hao, S.,, M. Mata,, D. Wolfe,, S. Huang,, J. C. Glorioso, and, D. J. Fink. 2003. HSV-mediated gene transfer of the glial cell-derived neurotrophic factor provides an antiallodynic effect on neuropathic pain. Mol. Ther. 8: 367375.
46. Hehir, K.,, D. M. Armentano,, L. M. Cardoza,, T. L. Choquette,, P. B. Berthelette,, G. A. White,, L. A. Couture,, M. B. Everton,, J. Keegan,, J. M. Martin,, D. A. Pratt,, M. P. Smith,, A. E. Smith, and, S. C. Wadsworth. 1996. Molecular characterization of replication-competent variants of adenovirus vector and genome modifications to prevent their occurrence. J. Virol. 70: 84598467.
47. Hernandez, Y. J.,, J. Wang,, W. G. Kearns,, S. Loiler,, A. Poirier, and, T. R. Flotte. 1999. Latent adeno-associated virus infection elicits humoral but not cell-mediated immune responses in a nonhuman primate model. J. Virol. 73: 85498558.
48. Herzog, R. W.,, J. N. Hagstrom,, S. H. Jung,, S. J. Tai,, J. M. Wilson,, K. J. Fisher, and, K. A. High. 1997. Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus. Proc. Natl. Acad. Sci. USA 94: 58045809.
49. Hollis, R. P.,, S. J. Nightingale,, X. Wang,, K. A. Pepper,, X. J. Yu,, L. Barsky,, G. M. Crooks, and, D. B. Kohn. 2006. Stable gene transfer to human CD34(+) hematopoietic cells using the Sleeping Beauty transposon. Exp. Hematol. 34: 13331343.
50. Huang, X.,, A. C. Wilber,, L. Bao,, D. Tuong,, J. Tolar,, P. J. Orchard,, B. L. Levine,, C. H. June,, R. S. McIvor,, B. R. Blazar, and, X. Zhou. 2006. Stable gene transfer and expression in human primary T cells by the Sleeping Beauty transposon system. Blood 107: 483491.
51. Ivics, Z.,, P. B. Hackett,, R. H. Plasterk, and, Z. Izsvák. 1997. Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 91: 501510.
52. Jiang, H.,, G. F. Pierce,, M. C. Ozelo,, E. V. de Paula,, J. A. Vargas,, P. Smith,, J. Sommer,, A. Luk,, C. S. Manno,, K. A. High, and, V. R. Arruda. 2006. Evidence of multiyear factor IX expression by AAV-mediated gene transfer to skeletal muscle in an individual with severe hemophilia B. Mol. Ther. 14: 452455.
53. Johnson, L. G.,, J. C. Olsen,, L. Naldini, and, R. C. Boucher. 2000. Pseudotyped human lentiviral vector-mediated gene transfer to airway epithelia in vivo. Gene Ther. 7: 568574.
54. Johnson, P.,, M. Wang, and, T. Friedmann. 1994. Improved cell survival by the reduction of immediate-early gene expression in replication-defective mutants of herpes simplex virus type 1 but not by mutation of the virion host shutoff function. J. Virol. 68: 63476362.
55. Johnson, P. R.,, B. C. Schnepp,, M. J. Connell,, D. Rohne,, S. Robinson,, G. R. Krivulka,, C. I. Lord,, R. Zinn,, D. C. Montefiori,, N. L. Letvin, and, K. R. Clark. 2005. Novel adeno-associated virus vector vaccine restricts replication of simian immunodeficiency virus in macaques. J. Virol. 79: 955965.
56. Jolly, D.,, E. Aguilar-Cordova, and, L. K. Aguilar. 2008. Adenovirus vectors: history and perspective, p. 39–59. In B. Dropulic and, B. J. Carter (ed.), Current Concepts in Genetic Medicine. John Wiley & Sons, New York, NY.
57. Kafri, T.,, U. Blömer,, D. A. Peterson,, F. H. Gage, and, I. M. Verma. 1997. Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat. Genet. 17: 314317.
58. Kang, Y.,, C. S. Stein,, J. A. Heth,, P. L. Sinn,, A. K. Penisten,, P. D. Staber,, K. L. Ratliff,, H. Shen,, C. K. Barker,, I. Martins,, C. M. Sharkey,, D. A. Sanders,, P. B. McCray, Jr., and, B. L. Davidson. 2002. In vivo gene transfer using a nonprimate lentiviral vector pseudotyped with Ross River virus glycoproteins. J. Virol. 76: 93789388.
59. Kasahara, N.,, A. M. Dozy, and, Y. W. Kan. 1994. Tissue-specific targeting of retroviral vectors through ligand-receptor interactions. Science 266: 13731376.
60. Khuri, F. R.,, J. Nemunaitis,, I. Ganly,, J. Arseneau,, I. F. Tannock,, L. Romel,, M. Gore,, J. Ironside,, R. H. MacDougall,, C. Heise,, B. Randlev,, A. M. Gillenwater,, P. Bruso,, S. B. Kaye,, W. K. Hong, and, D. H. Kirn. 2000. A controlled trial of intratumoral ONYX-015, a selectively replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat. Med. 6: 879885.
61. Kiem, H. P.,, J. Allen,, G. Trobridge,, E. Olson,, K. Keyser,, L. Peterson, and, D. W. Russell. 2007. Foamy-virus-mediated gene transfer to canine repopulating cells. Blood 109: 6570.
62. Kotin, R. M.,, M. Siniscalo,, R. J. Samulski,, X. D. Zhy,, L. Hunter,, C. A. Laughlin,, S. Mclaughlin,, N. Muzyczka,, M. Rocchi, and, K. I. Berns. 1990. Site-specific integration by AAV. Proc. Natl. Acad. Sci. USA 87: 22112215.
63. Krisky, D. M.,, D. Wolfe,, W. F. Goins,, P. C. Marconi,, R. Ramakrishnan,, M. Mata,, R. J. D. Rouse,, D. J. Fink, and, J. C. Glorioso. 1998. Deletion of multiple immediate early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons. Gene Ther. 5: 15931603.
64. Kubo, S.,, Y. Saeki,, E. A. Chiocca, and, K. Mitani. 2003. An HSV amplicon-based helper system for helper-dependent adenoviral vectors. Biochem. Biophys. Res. Commun. 307: 826830.
65. Levine, B. L.,, L. M. Humeau,, J. Boyer,, R. R. Mac-Gregor,, T. Rebello,, X. Lu,, G. K. Binder,, V. Slepushkin,, F. Lemiale,, J. R. Mascola,, F. D. Bushman,, B. Dropulic, and, C. H. June. 2006. Gene transfer in humans using a conditionally replicating lentiviral vector. Proc. Natl. Acad. Sci. USA 103: 1737217377.
66. Lewis, P. F.,, and M. Emerman. 1994. Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J. Virol. 68: 510516.
67. Lim, F.,, D. Hartley,, P. Starr,, P. Lang,, S. Song,, L. Yu,, Y. Wang, and, A. I. Geller. 1996. Generation of high-titer defective HSV-1 vectors using an IE 2 deletion mutant and quantitative study of expression in cultured cortical cells. BioTechniques 20: 460469.
68. Lin, S.,, N. Gaiano,, P. Culp,, J. C. Burns,, T. Friedmann,, J. K. Yee, and, N. Hopkins. 1994. Integration and germline transmission of a pseudotyped retroviral vector in zebrafish. Science 265: 666669.
69. Liu, B. L.,, M. Robinson,, Z. Q. Han,, R. H. Branston,, C. English,, P. Reay,, Y. McGrath,, S. K. Thomas,, M. Thornton,, P. Bullock,, C. A. Love, and, R. S. Coffin. 2003. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther. 10: 292303.
70. Lu, Y.,, T. A. McNearney,, W. Lin,, S. P. Wilson,, D. C. Yeomans, and, K. N. Westlund. 2007. Treatment of inflamed pancreas with enkephalin encoding HSV-1 recombinant vector reduces inflammatory damage and behavioral sequelae. Mol. Ther. 15: 18121819. [Epub ahead of print.]
71. Lusky, M. 2005. Good manufacturing practice production of adenoviral vectors for clinical trials. Hum. Gene Ther. 16: 281291.
72. Mack, C. A.,, S. R. Patel,, E. A. Schwarz,, P. Zanzonico,, R. T. Hahn,, A. Ilercil,, R. B. Devereux,, S. J. Goldsmith,, T. F. Christian,, T. A. Sandborn,, I. Kovesdi,, N. Hackett,, R. W. Isom,, R. G. Crystal, and, T. K. Rosengart. 1998. Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary DNA for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart. J. Thorac. Cardiovasc. Surg. 115: 168176.
73. Mangeot, P.-E.,, D. Nègre,, B. Dubois,, A. J. Winter,, P. Leissner,, M. Mehtali,, D. Kaiserlian,, F.-L. Cosset, and, J.-L. Darlix. 2000. Development of minimal lentivirus vectors derived from simian immunodeficiency virus (SIVmac251) and their use for gene transfer into human dendritic cells. J. Virol. 74: 83078315.
74. Mann, R.,, R. C. Mulligan, and, D. Baltimore. 1983. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 33: 153159.
75. Manno, C. S.,, V. R. Arruda,, G. F. Pierce,, B. Glader,, M. Ragni,, J. Rasko,, M. C. Ozelo,, K. Hoots,, P. Blatt,, B. Konkle,, M. Dake,, R. Kaye,, M Razavi,, A. Zajko,, J. Zehneder,, H. Nakai,, A. Chew,, D. Leonard,, J. F. Wright,, R. S. Lessard,, J. M. Sommer,, M. Tigges,, D. Sabatino,, A. Luk,, H. Jiang,, F. Mingozzi,, L. Couto,, H. C. Ertl,, K. A. High, and, M. A. Kay. 2006. Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat. Med. 12: 342347.
76. Markert, J. M.,, G. Y. Gillespie,, R. R. Weichselbaum,, B. Roizman, and, R. J. Whitley. Genetically engineered HSV in the treatment of glioma: a review. Rev. Med. Virol. 10: 1730.
77. Markert, J. M.,, M. D. Medlock,, S. D. Rabkin,, G. Y. Gillespie,, T. Todo,, W. D. Hunter,, C. A. Palmer,, F. Feigenbaum,, C. Tornatore,, F. Tufaro, and, R. L. Martuza. 2000. Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Ther. 7: 867874.
78. May, C.,, S. Rivella,, J. Callegari,, G. Heller,, K. M. Gaensler,, L. Luzzatto, and, M. Sadelain. 2000. Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. Nature 406: 8286.
79. McConnell, M. J.,, and M. J. Imperiale. 2004. Biology of adenovirus and its use as a vector for gene therapy. Hum. Gene Ther. 15: 10221033.
80. Meunier, A.,, A. Latremoliere,, A. Mauborgne,, S. Bourgoin,, V. Kayser,, F. Cesselin,, M. Hamon, and, M. Pohl. 2005. Attenuation of pain-related behavior in a rat model of trigeminal neuropathic pain by viral-driven enkephalin overproduction in trigeminal ganglion neurons. Mol. Ther. 11: 608616.
81. Miller, A. D. 1990. Retrovirus packaging cells. Hum. Gene Ther. 1: 514.
82. Mingozzi, F.,, M. V. Maus,, D. J. Hiu,, D. E. Sabatino,, S. L. Murphy,, J. E. Rasko,, M. V. Ragni,, C. S. Manno,, J. Sommer,, H. Jiang,, G. F. Pierce,, H. C. J. Ertl, and, K. A. High. 2007. CD8+ T-cell responses to adeno-associated virus capsid in humans. Nat. Med. 13: 419422.
83. Mitchell, R. S.,, B. F. Beitzel,, A. R. Schroder,, P. Shinn,, H. Chen,, C. C. Berry,, J. R. Ecker, and, F. D. Bushman. 2004. Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol. 2: E234.
84. Miyoshi, H.,, K. A. Smith,, D. E. Mosier,, I. M. Verma, and, B. E. Torbett. 1999. Transduction of human CE34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors. Science 283: 682686.
85. Moss, R. B.,, D. Rodman,, L. T. Spencer,, M. L. Aitken,, P. L. Zeitlen,, D. Waltz,, C. Milla,, A. S. Brody,, J. P. Clancy,, B. Ramsey,, N. Hamblett, and, A. E. Heald. 2004. Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis. Chest 125: 509521.
86. Moss, R. B.,, C. Milla,, J. Colombo,, F. Accurso,, P. L. Zeitlin,, J. P. Clancy,, L. T. Spencer,, J. Pilewski,, D. A. Waltz,, H. Dorkin,, T. Ferkol,, M. Pian,, B. Ramsey,, B. J. Carter,, D. Martin, and, A. E. Heald. 2007. Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis. A randomized placebo-controlled phase 2B trial. Hum. Gene Ther. 18: 726732.
87. Muruve, D. 2004. The innate immune response to adenovirus vectors. Hum. Gene Ther. 15: 11571166.
88. Muzyczka, N.,, and K. H. Warrington. 2005. Custom adeno-associated virus capsids: the next generation of recombinant vectors with novel tropism. Hum. Gene Ther. 16: 408416.
89. Nakai, H.,, R. W. Herzog,, J. Hagstrom,, J. Walter,, S. H. Kung,, E. Y. Yang,, S. J. Tsai,, Y. Iwaki,, G. Kurtzman,, K. J. Fisher,, P. Colosi,, L. B. Couto, and, K. A. High. 1998. Adeno-associated viral vector-mediated gene transfer of human blood coagulation factor IX into mouse liver. Blood 91: 46004607.
90. Naldini, L.,, U. Blömer,, F. H. Gage,, D. Trono, and, I. M. Verma. 1996. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc. Natl. Acad. Sci. USA 93: 1138211388.
91. Naldini, L.,, U. Blömer,, P. Gallay,, D. Ory,, R. Mulligan,, F. H. Gage,, I. M. Verma, and, D. Trono. 1996. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272: 263267.
92. Naviaux, R. K.,, E. Costanzi,, M. Haas, and, I. M. Verma. 1996. The pCL vector system: rapid production of helper-free, high-titer, recombinant retroviruses. J. Virol. 70: 57015705.
93. Oehmig, A.,, C. Fraefel,, X. O. Breakefield, and, M. Ackermann. 2004. Herpes simplex virus type 1 amplicons and their hybrid virus partners, EBV, AAV, and retrovirus. Curr. Gene Ther. 4: 385408.
94. Olsen, J. C. 1998. Gene transfer vectors derived from equine infectious anemia virus. Gene Ther. 5: 14811487.
95. Ott, M. G.,, M. Schmidt,, K. Schwarzwaelder,, S. Stein,, U. Siler,, U. Koehl,, H. Glimm,, K. Kuhlcke,, A. Schilz,, H. Kunkel,, S. Naundorf,, A. Brinkmann,, A. Deichmann,, M. Fischer,, C. Ball,, I. Pilz,, C. Dunbar,, Y. Du,, N. A. Jenkins,, N. G. Copeland,, U. Luthi,, M. Hassan,, A. J. Thrasher,, D. Hoelzer,, C. von Kalle,, R. Seger, and, M. Grez. 2006. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat. Med. 12: 401409.
96. Papanastassiou, V.,, R. Rampling,, M. Fraser,, R. Petty,, D. Hadley,, J. Nicoll,, J. Harland,, R. Mabbs, and, M. Brown. 2002. The potential for efficacy of the modified (ICP 34.5(–)) herpes simplex virus HSV1716 following intratumoural injection into human malignant glioma: a proof of principle study. Gene Ther. 9: 398406.
97. Pear, W. S.,, G. P. Nolan,, M. L. Scott, and, D. Baltimore. 1993. Production of high-titer helper-free retroviruses by transient transfection. Proc. Natl. Acad. Sci. USA 90: 83928396.
98. Peluso, R. W. 2008. The manufacture of adeno-associated viral vectors, p. 245–252. In B. Dropulic and, B. J. Carter (ed.), Current Concepts in Genetic Medicine. John Wiley & Sons, New York, NY.
99. Peng, Z. 2005. Current status of gendicine in China: recombinant human Ad-p53 for treatment of cancers. Hum. Gene Ther. 16: 10161027.
100. Poeschla, E. M.,, F. Wong-Staal, and, D. J. Looney. 1998. Efficient transduction of nondividing human cells by feline immunodeficiency virus lentiviral vectors. Nat. Med. 4: 354357.
101. Porter, C. D.,, M. K. Collins,, C. S. Tailor,, M. H. Parkar,, F. L. Cosset,, R. A. Weiss, and, Y. Takeuchi. 1996. Comparison of efficiency of infection of human gene therapy target cells via four different retroviral receptors. Hum. Gene Ther. 7: 913919.
102. Poznansky, M.,, A. Lever,, L. Bergeron,, W. Haseltine, and, J. Sodroski. 1991. Gene transfer into human lymphocytes by a defective human immunodeficiency virus type 1 vector. J. Virol. 65: 532536.
103. Puskovic, V.,, D. Wolfe,, J. Goss,, S. Huang,, M. Mata,, J. C. Glorioso, and, D. J. Fink. 2004. Prolonged biologically active transgene expression driven by HSV LAP2 in brain in vivo. Mol. Ther. 10: 6775.
104. Rampling, R.,, G. Cruickshank,, V. Papanastassiou,, J. Nicoll,, D. Hadley,, D. Brennan,, R. Petty,, A. MacLean,, J. Harland,, E. McKie,, R. Mabbs, and, M. Brown. 2000. Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther. 7: 859866.
105. Raper, S. E.,, N. Chirmule,, F. S. Lee,, N. A. Wivel,, A. Bagg,, G. P. Gao,, J. M. Wilson, and, M. L. Batshaw. 2003. Fatal systemic inflammatory response syndrome in a [sic] ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol. Genet. Metab. 80: 148158.
106. Rasheed, S.,, M. B. Gardner, and, E. Chan. 1976. Amphotropic host range of naturally occurring wild mouse leukemia viruses. J. Virol. 19: 1318.
107. Rissanen, T. T.,, and S. Yla-Herttuala. 2007. Current status of cardiovascular gene therapy. Mol. Ther. 15: 12331247.
108. Rock, D. L.,, A. B. Nesburn,, H. Ghiasi,, J. Ong,, T. L. Lewis,, J. R. Lokensgard, and, S. L. Wechsler. 1987. Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1. J. Virol. 61: 38203826.
109. Samaniego, L. A.,, L. Neiderhiser, and, N. A. DeLuca. 1998. Persistence and expression of the herpes simplex virus genome in the absence of immediate-early proteins. J. Virol. 72: 33073320.
110. Sandalon, Z.,, E. M. Bruckheimer,, K. H. Lustig, and, H. Burstein. 2007. Long-term suppression of experimental arthritis following intramuscular administration of a pseudotyped AAV2/TNFR:Fc vector. Mol. Ther. 15: 264269.
111. Schauber-Plewa, C.,, A. Simmons,, M. J. Tuerk,, C. D. Pacheco, and, G. Veres. 2005. Complement regulatory proteins are incorporated into lentiviral vectors and protect particles against complement inactivation. Gene Ther. 12: 238245.
112. Schnepp, B. C.,, K. R. Clark,, D. L. Klemanski,, C. A. Pacak, and, P. R. Johnson. 2003. Genetic fate of recombinant adeno-associated virus vector genomes in muscle. J. Virol. 77: 34953504.
113. Schnepp, B. C.,, R. L. Jensen,, C. L. Chen,, P. R. Johnson, and, K. R. Clark. 2005. Characterization of adeno-associated genomes isolated from human tissues. J. Virol. 79: 1479314803.
114. Schroder, A. R.,, P. Shinn,, H. Chen,, C. Berry,, J. R. Ecker, and, F. Bushman. 2002. HIV-1 integration in the human genome favors active genes and local hotspots. Cell 110: 521529.
115. Schuettrumpf, J.,, J. H. Liu,, L. B. Couto,, K. Addya,, D. G. B. Leonard,, Z. Zhen,, J. Sommer, and, V. R. Arruda. 2006. Inadvertent germline transmission of AAV2 vector: findings in a rabbit model correlate with those in a human clinical trial. Mol. Ther. 13: 10641073.
116. Shen, Y.,, and J. Nemunaitis. 2006. Herpes simplex virus 1 (HSV-1) for cancer treatment. Cancer Gene Ther. 13: 975992.
117. Shimada, T.,, H. Fujii,, H. Mitsuya, and, A. W. Nienhuis. 1991. Targeted and highly efficient gene transfer into CD34+ cells by a recombinant human immunodeficiency virus retroviral vector. J. Clin. Invest. 88: 10431047.
118. Smith, J. S.,, J. Tian,, J. N. Lozier, and, A. P. Byrnes. 2004. Severe pulmonary pathology after intravenous administration of adenovirus vectors in cirrhotic rats. Mol. Ther. 9: 932941.
119. Soignier, R. D.,, A. L. Vaccarino,, A. M. Brennan,, A. J. Kastin, and, J. E. Zadina. 2000. Analgesic effects of endomorphin-1 and endomorphin-2 in the formalin test in mice. Life Sci. 67: 907912.
120. Soneoka, Y.,, P. M. Cannon,, E. E. Ramsdale,, J. C. Griffiths,, G. Romano,, S. M. Kingsman, and, A. J. Kingsman. 1995. A transient three-plasmid expression system for the production of high titer retroviral vectors. Nucleic Acids Res. 23: 628633.
121. Spaete, R.,, and N. Frenkel. 1982. The herpes simplex virus amplicon: a new eucaryotic defective-virus cloning amplifying vector. Cell 30: 295304.
122. Spivack, J. G.,, and N. W. Fraser. 1987. Detection of herpes simplex virus type 1 transcripts during latent infection in mice. J. Virol. 61: 38413847.
123. Stevens, J. G.,, E. K. Wagner,, G. B. Devi-Rao,, M. L. Cook, and, L. T. Feldman. 1987. RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science 235: 10561059.
124. Sutton, R. E.,, H. T. Wu,, R. Rigg,, E. Bohnlein, and, P. O. Brown. 1998. Human immunodeficiency virus type 1 vectors efficiently transduce human hematopoietic stem cells. J. Virol. 72: 57815788.
125. Thyagarajan, B.,, E. C. Olivares,, R. P. Hollis,, D. S. Ginsburg, and, M. P. Calos. 2001. Site-specific genomic integration in mammalian cells mediated by phage phiC31 integrase. Mol. Cell. Biol. 21: 39263934.
126. Trobridge, G. D.,, D. G. Miller,, M. A. Jacobs,, J. M. Allen,, H. P. Kiem,, R. Kaul, and, D. W. Russell. 2006. Foamy virus vector integration sites in normal human cells. Proc. Natl. Acad. Sci. USA 103: 14981503.
127. Trobridge, G. D.,, and D. W. Russell. 1998. Helper-free foamy virus vectors. Hum. Gene Ther. 9: 25172525.
128. Wade-Martins, R.,, Y. Saeki, and, E. A. Chiocca. 2003. Infectious delivery of a 135-kb LDLR genomic locus leads to regulated complementation of low-density lipoprotein receptor deficiency in human cells. Mol. Ther. 7: 604612.
129. Willis, R. C.,, D. J. Jolly,, A. D. Miller,, M. M. Plent,, A. C. Esty,, P. J. Anderson,, H. C. Chang,, O. W. Jones,, J. E. Seegmiller, and, T. Friedmann. 1984. Partial phenotypic correction of human Lesch-Nyhan (hypoxanthine-guanine phosphoribosyltransferasedeficient) lymphoblasts with a transmissible retroviral vector. J. Biol. Chem. 259: 78427849.
130. Wolfe, D.,, W. F. Goins,, T. J. Kaplan,, S. V. Capuano,, J. Fradette,, M. Murphey-Corb,, J. B. Cohen,, P. D. Robbins, and, J. C. Glorioso. 2001. Systemic delivery of nerve growth factor following herpesvirus gene transfer. Mol. Ther. 3: 6169.
131. Wu, X.,, Y. Li,, B. Crise, and, S. M. Burgess. 2003. Transcription start regions in the human genome are favored targets for MLV integration. Science 300: 17491751.
132. Wu, X.,, J. K. Wakefield,, H. Liu,, H. Xiao,, R. Kralovics,, J. T. Prchal, and, J. C. Kappes. 2000. Development of a novel trans-lentiviral vector that affords predictable safety. Mol. Ther. 2: 4755.
133. Xiao, W.,, N. Chirmule,, M. A. Schnell,, J. Tazelaar,, J. V. Hughes, and, J. M. Wilson. 2000. Route of administration determines induction of T-cell independent humoral responses to adeno-associated virus vectors. Mol. Ther. 1: 323329.
134. Yang, L.,, L. Bailey,, D. Baltimore, and, P. Wang. 2006. Targeting lentiviral vectors to specific cell types in vivo. Proc. Natl. Acad. Sci. USA 103: 1147911484.
135. Yant, S. R.,, L. Meuse,, W. Chiu,, Z. Ivics,, Z. Izsvak, and, M. A. Kay. 2000. Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system. Nat. Genet. 25: 3541.
136. Yei, S.,, N. Mittereder,, K. Tang,, C. O. Sullivan, and, B. C. Trapnell. 1994. Adenovirus-mediated gene transfer for cystic fibrosis: quantitative evaluation of repeated in vivo vector administration to the lung. Gene Ther. 1: 192200.
137. Yeomans, D. C.,, S. R. Levinson,, M. C. Peters,, A. G. Koszowski,, A. Z. Tzabazis,, W. F. Gilly, and, S. P. Wilson. 2005. Decrease in inflammatory hyperalgesia by herpes vector-mediated knockdown of Nav1.7 sodium channels in primary afferents. Hum. Gene Ther. 16: 271277.
138. Yoshimura, N.,, M. E. Franks,, K. Sasaki,, W. F. Goins,, J. Goss,, T. Yokoyama,, M. O. Fraser,, S. Seki,, J. Fink,, J. Glorioso,, W. C. de Groat, and, M. B. Chancellor. 2001. Gene therapy of bladder pain with herpes simplex virus (HSV) vectors expressing preproenkephalin (PPE). Urology 57: 116.
139. Zabner, J.,, D. M. Petersen,, A. P. Puga,, S. M. Graham,, L. A. Couture,, L. D. Keyes,, M. J. Lukason,, J. A. St. George,, R. J. Gregory, and, A. E. Smith. 1994. Safety and efficacy of repetitive adenovirus-mediated gene transfer of CFTR cDNA to airway epithelia of primates and cotton rats. Nat. Genet. 6: 7583.
140. Zadina, J. E. 2002. Isolation and distribution of endomorphins in the central nervous system. Jpn. J. Pharmacol. 89: 203208.
141. Zufferey, R.,, T. Dull,, R. J. Mandel,, A. Bukovsky,, D. Quiroz,, L. Naldini, and, D. Trono. 1998. Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J. Virol. 72: 98739880.
142. Zufferey, R.,, D. Nagy,, R. J. Mandel,, L. Naldini, and, D. Trono. 1997. Multiple attenuated lentiviral vectors achieve efficient gene delivery in vivo. Nat. Biotechnol. 15: 871875.


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Clinical applications of gene therapy

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16
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Comparison of genetic vectors

Citation: Kohn D, Carter B, Grandi P, Glorioso J. 2009. Gene Therapy and Viruses, p 351-370. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch16

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