Adeno-associated virus vector integration (2024)

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1. McCarty DM, Young SM, Jr, Samulski RJ. Integration of adeno-associated virus (AAV) and recombinant AAV vectors. Annu Rev Genet. 2004;38:819–845. [PubMed] [Google Scholar]

2. Russell DW, Kay MA. Adeno-associated virus vectors and hematology. Blood. 1999;94(3):864–874. [PMC free article] [PubMed] [Google Scholar]

3. Schnepp BC, Jensen RL, Chen CL, Johnson PR, Clark KR. Characterization of adeno-associated virus genomes isolated from human tissues. J Virol. 2005;79(23):14793–14803. [PMC free article] [PubMed] [Google Scholar]

4. Chen CL, Jensen RL, Schnepp BC, Connell MJ, Shell R, Sferra TJ, Bartlett JS, Clark KR, Johnson PR. Molecular characterization of adeno-associated viruses infecting children. J Virol. 2005;79(23):14781–14792. [PMC free article] [PubMed] [Google Scholar]

5. Gao G, Vandenberghe LH, Alvira MR, Lu Y, Calcedo R, Zhou X, Wilson JM. Clades of adeno-associated viruses are widely disseminated in human tissues. J Virol. 2004;78(12):6381–6388. [PMC free article] [PubMed] [Google Scholar]

6. Gao G, Alvira MR, Somanathan S, Lu Y, Vandenberghe LH, Rux JJ, Calcedo R, Sanmiguel J, Abbas Z, Wilson JM. Adeno-associated viruses undergo substantial evolution in primates during natural infections. Proc Natl Acad Sci USA. 2003;100(10):6081–6086. [PMC free article] [PubMed] [Google Scholar]
AAV genomes were detected and isolated by PCR in multiple tissues from non-human primates. Southern blot analysis suggested that the AAV genome can persist in cells as both integrated and non-integrated forms. This paper provided unexpected evidence that AAV infections can spread efficiently throughout the body.

7. Gao GP, Alvira MR, Wang L, Calcedo R, Johnston J, Wilson JM. Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci USA. 2002;99(18):11854–11859. [PMC free article] [PubMed] [Google Scholar]

8. Samulski RJ, Zhu X, Xiao X, Brook JD, Housman DE, Epstein N, Hunter LA. Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J. 1991;10(12):3941–3950. [PMC free article] [PubMed] [Google Scholar]

9. Kotin RM, Siniscalco M, Samulski RJ, Zhu XD, Hunter L, Laughlin CA, McLaughlin S, Muzyczka N, Rocchi M, Berns KI. Site-specific integration by adeno-associated virus. Proc Natl Acad Sci USA. 1990;87(6):2211–2215. [PMC free article] [PubMed] [Google Scholar]

10. Kotin RM, Linden RM, Berns KI. Characterization of a preferred site on human chromosome 19q for integration of adeno-associated virus DNA by non-hom*ologous recombination. EMBO J. 1992;11(13):5071–5078. [PMC free article] [PubMed] [Google Scholar]

11. Mehrle S, Rohde V, Schlehofer JR. Evidence of chromosomal integration of AAV DNA in human testis tissue. Virus Genes. 2004;28(1):61–69. [PubMed] [Google Scholar]
Two virus:chromosome junctions were isolated from human testicular tissue by ‘genome-walking’ PCR. The isolation of these virus:chromosome junctions demonstrated that AAV can integrate in the testes after infection. These findings raise the possibility that AAV vectors can integrate in spermatogonia and perhaps be transferred by germ-line transmission.

12. Drew HR, Lockett LJ, Both GW. Increased complexity of wild-type adeno-associated virus-chromosomal junctions as determined by analysis of unselected cellular genomes. J Gen Virol. 2007;88(Pt 6):1722–1732. [PubMed] [Google Scholar]

13. Grimm D, Kern A, Rittner K, Kleinschmidt JA. Novel tools for production and purification of recombinant adenoassociated virus vectors. Hum Gene Ther. 1998;9(18):2745–2760. [PubMed] [Google Scholar]

14. Zhong L, Zhou X, Li Y, Qing K, Xiao X, Samulski RJ, Srivastava A. Single-polarity recombinant adeno-associated virus 2 vector-mediated transgene expression in vitro and in vivo: Mechanism of transduction. Mol Ther. 2008;16(2):290–295. [PubMed] [Google Scholar]

15. Thomas CE, Storm TA, Huang Z, Kay MA. Rapid uncoating of vector genomes is the key to efficient liver transduction with pseudotyped adeno-associated virus vectors. J Virol. 2004;78(6):3110–3122. [PMC free article] [PubMed] [Google Scholar]

16. Zhou X, Zeng X, Fan Z, Li C, McCown T, Samulski RJ, Xiao X. Adeno-associated virus of a single-polarity DNA genome is capable of transduction in vivo. Mol Ther. 2008;16(3):494–499. [PubMed] [Google Scholar]

17. Nakai H, Storm TA, Kay MA. Recruitment of single-stranded recombinant adeno-associated virus vector genomes and intermolecular recombination are responsible for stable transduction of liver in vivo. J Virol. 2000;74(20):9451–9463. [PMC free article] [PubMed] [Google Scholar]

18. Duan D, Yan Z, Yue Y, Engelhardt JF. Structural analysis of adeno-associated virus transduction circular intermediates. Virology. 1999;261(1):8–14. [PubMed] [Google Scholar]

19. Duan D, Sharma P, Yang J, Yue Y, Dudus L, Zhang Y, Fisher KJ, Engelhardt JF. Circular intermediates of recombinant adeno-associated virus have defined structural characteristics responsible for long-term episomal persistence in muscle tissue. J Virol. 1998;72(11):8568–8577. [PMC free article] [PubMed] [Google Scholar]

20. Nakai H, Yant SR, Storm TA, Fuess S, Meuse L, Kay MA. Extrachromosomal recombinant adeno-associated virus vector genomes are primarily responsible for stable liver transduction in vivo. J Virol. 2001;75(15):6969–6976. [PMC free article] [PubMed] [Google Scholar]

21. Gao G, Lu Y, Calcedo R, Grant RL, Bell P, Wang L, Figueredo J, Lock M, Wilson JM. Biology of AAV serotype vectors in liver-directed gene transfer to nonhuman primates. Mol Ther. 2006;13(1):77–87. [PubMed] [Google Scholar]

22. Grimm D, Pandey K, Nakai H, Storm TA, Kay MA. Liver transduction with recombinant adeno-associated virus is primarily restricted by capsid serotype not vector genotype. J Virol. 2006;80(1):426–439. [PMC free article] [PubMed] [Google Scholar]

23. Rutledge EA, Russell DW. Adeno-associated virus vector integration junctions. J Virol. 1997;71(11):8429–8436. [PMC free article] [PubMed] [Google Scholar]

24. Yang CC, Xiao X, Zhu X, Ansardi DC, Epstein ND, Frey MR, Matera AG, Samulski PJ. Cellular recombination pathways and viral terminal repeat hairpin structures are sufficient for adeno-associated virus integration in vivo and in vitro. J Virol. 1997;71(12):9231–9247. [PMC free article] [PubMed] [Google Scholar]

25. Miao CH, Snyder RO, Schowalter DB, Patijn GA, Donahue B, Winther B, Kay MA. The kinetics of rAAV integration in the liver. Nat Genet. 1998;19(1):13–15. [PubMed] [Google Scholar]

26. Russell DW, Miller AD, Alexander IE. Adeno-associated virus vectors preferentially transduce cells in S phase. Proc Natl Acad Sci USA. 1994;91(19):8915–8919. [PMC free article] [PubMed] [Google Scholar]

27. Hirata R, Chamberlain J, Dong R, Russell DW. Targeted transgene insertion into human chromosomes by adeno-associated virus vectors. Nat Biotechnol. 2002;20(7):735–738. [PubMed] [Google Scholar]

28. Ponnazhagan S, Erikson D, Kearns WG, Zhou SZ, Nahreini P, Wang XS, Srivastava A. Lack of site-specific integration of the recombinant adeno-associated virus 2 genomes in human cells. Hum Gene Ther. 1997;8(3):275–284. [PubMed] [Google Scholar]

29. Kearns WG, Afione SA, Fulmer SB, Pang MC, Erikson D, Egan M, Landrum MJ, Flotte TR, Cutting GR. Recombinant adeno-associated virus (AAV-CFTR) vectors do not integrate in a site-specific fashion in an immortalized epithelial cell line. Gene Ther. 1996;3(9):748–755. [PubMed] [Google Scholar]

30. McLaughlin SK, Collis P, Hermonat PL, Muzyczka N. Adeno-associated virus general transduction vectors: Analysis of proviral structures. J Virol. 1988;62(6):1963–1973. [PMC free article] [PubMed] [Google Scholar]

31. Lebkowski JS, McNally MM, Okarma TB, Lerch LB. Adeno-associated virus: A vector system for efficient introduction and integration of DNA into a variety of mammalian cell types. Mol Cell Biol. 1988;8(10):3988–3996. [PMC free article] [PubMed] [Google Scholar]

32. Samulski PJ, Chang LS, Shenk T. Helper-free stocks of recombinant adeno-associated viruses: Normal integration does not require viral gene expression. J Virol. 1989;63(9):3822–3828. [PMC free article] [PubMed] [Google Scholar]

33. Miller DG, Rutledge EA, Russell DW. Chromosomal effects of adeno-associated virus vector integration. Nat Genet. 2002;30(2):147–148. [PubMed] [Google Scholar]

34. Miller DG, Trobridge GD, Petek LM, Jacobs MA, Kaul R, Russell DW. Large-scale analysis of adeno-associated virus vector integration sites in normal human cells. J Virol. 2005;79(17):11434–11442. [PMC free article] [PubMed] [Google Scholar]
Reported the analysis of 977 AAV vector:chromosome junctions and integration sites in human fibroblasts. This study was the first large-scale analysis of provirus integration sites in human cells and characterization of these junctions provided a representation of insertional mutagenesis by AAV vectors and an improved knowledge of AAV integration.

35. Nakai H, Iwaki Y, Kay MA, Couto LB. Isolation of recombinant adeno-associated virus vector-cellular DNA junctions from mouse liver. J Virol. 1999;73(7):5438–5447. [PMC free article] [PubMed] [Google Scholar]

36. Nakai H, Montini E, Fuess S, Storm TA, Grompe M, Kay MA. AAV serotype 2 vectors preferentially integrate into active genes in mice. Nat Genet. 2003;34(3):297–302. [PubMed] [Google Scholar]

37. Nakai H, Wu X, Fuess S, Storm TA, Munroe D, Montini E, Burgess SM, Grompe M, Kay MA. Large-scale molecular characterization of adeno-associated virus vector integration in mouse liver. J Virol. 2005;79(6):3606–3614. [PMC free article] [PubMed] [Google Scholar]••
An analysis of 347 AAV vector:chromosome junctions from mouse livers provided definitive evidence for significant in vivo integration by AAV vectors. Integration site preferences were described and integration occurred preferentially in transcribed genes in this study.

38. Inagaki K, Lewis SM, Wu X, Ma C, Munroe DJ, Fuess S, Storm TA, Kay MA, Nakai H. DNA palindromes with a modest arm length of greater, similar 20 base pairs are a significant target for recombinant adeno-associated virus vector integration in the liver, muscles, and heart in mice. J Virol. 2007;81(20):11290–11303. [PMC free article] [PubMed] [Google Scholar]••
Reported the isolation of multiple independent vector:chromosome junctions from different mouse tissues. An analysis of the integration sites showed that AAV vectors integrate near DNA palindromes. This was the first demonstration of integration in tissues other than the liver after vector delivery.

39. Han Z, Zhong L, Maina N, Hu Z, Li X, Chouthai NS, Bischof D, Weigel-Van Aken KA, Slayton WB, Yoder MC, Srivastava A. Stable integration of recombinant adeno-associated virus vector genomes after transduction of murine hematopoietic stem cells. Hum Gene Ther. 2008;19(3):267–278. [PubMed] [Google Scholar]

40. Pachori AS, Melo LG, Zhang L, Loda M, Pratt RE, Dzau VJ. Potential for germ line transmission after intramyocardial gene delivery by adeno-associated virus. Biochem Biophys Res Commun. 2004;313(3):528–533. [PubMed] [Google Scholar]

41. Wu P, Phillips MI, Bui J, Terwilliger EF. Adeno-associated virus vector-mediated transgene integration into neurons and other nondividing cell targets. J Virol. 1998;72(7):5919–5926. [PMC free article] [PubMed] [Google Scholar]

42. Mitchell RS, Beitzel BF, Schroder AR, Shinn P, Chen H, Berry CC, Ecker JR, Bushman FD. Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol. 2004;2(8):E234. [PMC free article] [PubMed] [Google Scholar]

43. Hematti P, Hong BK, Ferguson C, Adler R, Hanawa H, Sellers S, Holt IE, Eckfeldt CE, Sharma Y, Schmidt M, von Kalle C. Distinct genomic integration of MLV and SIV vectors in primate hematopoietic stem and progenitor cells. PLoS Biol. 2004;2(12):e423. [PMC free article] [PubMed] [Google Scholar]

44. Wu X, Li Y, Crise B, Burgess SM. Transcription start regions in the human genome are favored targets for MLV integration. Science. 2003;300(5626):1749–1751. [PubMed] [Google Scholar]

45. Miller DG, Petek LM, Russell DW. Adeno-associated virus vectors integrate at chromosome breakage sites. Nat Genet. 2004;36(7):767–773. [PubMed] [Google Scholar]••
AAV vectors integrated at induced chromosome double-strand breaks. The sequences of vector proviruses in relation to the location of the double-strand breaks were consistent with integration via the non-hom*ologous end-joining repair pathway. This paper provided direct evidence that AAV vectors integrate at pre-existing chromosomal breaks.

46. O'Neill JP, Finette BA. Transition mutations at CpG dinucleotides are the most frequent in vivo spontaneous single-based substitution mutation in the human HPRT gene. Environ Mol Mutagen. 1998;32(2):188–191. [PubMed] [Google Scholar]

47. Tazi J, Bird A. Alternative chromatin structure at CpG islands. Cell. 1990;60(6):909–920. [PubMed] [Google Scholar]

48. Wolf SF, Migeon BR. Clusters of CpG dinucleotides implicated by nuclease hypersensitivity as control elements of housekeeping genes. Nature. 1985;314(6010):467–469. [PubMed] [Google Scholar]

49. Kobayashi T. Strategies to maintain the stability of the ribosomal RNA gene repeats – Collaboration of recombination, cohesion, and condensation. Genes Genet Syst. 2006;81(3):155–161. [PubMed] [Google Scholar]

50. Bailey JA, Eichler EE. Primate segmental duplications: Crucibles of evolution, diversity and disease. Nat Rev Genet. 2006;7(7):552–564. [PubMed] [Google Scholar]

51. Shaw CJ, Lupski JR. Implications of human genome architecture for rearrangement-based disorders: The genomic basis of disease. Hum Mol Genet. 2004;13(Suppl 1):R57–R64. [PubMed] [Google Scholar]

52. Aguilera A. The connection between transcription and genomic instability. EMBO J. 2002;21(3):195–201. [PMC free article] [PubMed] [Google Scholar]

53. Bell P, Wang L, Lebherz C, Flieder DB, Bove MS, Wu D, Gao GP, Wilson JM, Wivel NA. No evidence for tumorigenesis of AAV vectors in a large-scale study in mice. Mol Ther. 2005;12(2):299–306. [PubMed] [Google Scholar]

54. Schuettrumpf J, Baila S, Khazi F, Liu JH, Bunte R, Arruda V. AAV vectors do not increase the risk of tumor formation in p53 deficient models. Mol Ther. 2007;15(Suppl 1):S1. [Google Scholar]

55. Embury JE, Charron CC, Poirier AE, Zori A, Carmichael R, Flotte TR, Laipis PJ. Long term portal vein administration of AAV-WPRE vector results in increased incidence of neoplastic disease and hepatic pathology. Mol Ther. 2006;13(Suppl 1) Abs 216. [Google Scholar]

56. Grimm D, Beer S, Komatsubara K, Lee JS, Koh S, Wang L, Storm TA, Davis CR, Kay MA, Felsher D. Adverse shRNA cytotoxicity can accelerate tumorgenesis in genetically predisposed mice. Mol Ther. 2007;15(Suppl 1):S266. [Google Scholar]

57. Bell P, Moscioni AD, McCarter RJ, Wu D, Gao G, Hoang A, Sanmiguel JC, Sun X, Wivel NA, Raper SE, Furth EE, et al. Analysis of tumors arising in male B6C3F1 mice with and without AAV vector delivery to liver. Mol Ther. 2006;14(1):34–44. [PubMed] [Google Scholar]

58. Donsante A, Vogler C, Muzyczka N, Crawford JM, Barker J, Flotte T, Campbell-Thompson M, Daly T, Sands MS. Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors. Gene Ther. 2001;8(17):1343–1346. [PubMed] [Google Scholar]

59. Donsante A, Miller DG, Li Y, Vogler C, Brunt EM, Russell DW, Sands MS. AAV vector integration sites in mouse hepatocellular carcinoma. Science. 2007;317(5837):477. [PubMed] [Google Scholar]••
Newborn mice injected with an AAV vector developed hepatocellular carcinoma. The region of chromosome 12 where the four integrated proviruses were observed in tumors contains multiple maternally and paternally imprinted genes. Microarray analysis showed upregulation of nearby transcripts. These data provide compelling evidence that AAV integration can be associated with tumorigenesis.

60. Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt P, Konkle B, Dake M, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med. 2006;12(3):342–347. [PubMed] [Google Scholar]

61. Chamberlain JR, Deyle DR, Schwarze U, Wang P, Hirata RK, Li Y, Byers PH, Russell DW. Gene targeting of mutant COL1A2 alleles in mesenchymal stem cells from individuals with osteogenesis imperfecta. Mol Ther. 2008;16(1):187–193. [PMC free article] [PubMed] [Google Scholar]

62. Chamberlain JR, Schwarze U, Wang PR, Hirata RK, Hankenson KD, Pace JM, Underwood RA, Song KM, Sussman M, Byers PH, Russell DW. Gene targeting in stem cells from individuals with osteogenesis imperfecta. Science. 2004;303(5661):1198–1201. [PubMed] [Google Scholar]••
Mesenchymal stem cells from patients with osteogenesis imperfecta were infected with an AAV gene-targeting vector designed to disrupt the COL1A1 gene. After selection, Southern blot analysis demonstrated that 31 to 90% of cells were targeted at the COL1A1 gene. This was the first demonstration of gene targeting in adult human stem cells.

63. Inoue N, Dong R, Hirata RK, Russell DW. Introduction of single base substitutions at hom*ologous chromosomal sequences by adeno-associated virus vectors. Mol Ther. 2001;3(4):526–530. [PubMed] [Google Scholar]

64. Inoue N, Hirata RK, Russell DW. High-fidelity correction of mutations at multiple chromosomal positions by adeno-associated virus vectors. J Virol. 1999;73(9):7376–7380. [PMC free article] [PubMed] [Google Scholar]

65. Kohli M, Rago C, Lengauer C, Kinzler KW, Vogelstein B. Facile methods for generating human somatic cell gene knockouts using recombinant adeno-associated viruses. Nucleic Acids Res. 2004;32(1):e3. [PMC free article] [PubMed] [Google Scholar]

66. Hendrie PC, Hirata RK, Russell DW. Chromosomal integration and hom*ologous gene targeting by replication-incompetent vectors based on the autonomous parvovirus minute virus of mice. J Virol. 2003;77(24):13136–13145. [PMC free article] [PubMed] [Google Scholar]

67. Miller DG, Petek LM, Russell DW. Human gene targeting by adeno-associated virus vectors is enhanced by DNA double-strand breaks. Mol Cell Biol. 2003;23(10):3550–3557. [PMC free article] [PubMed] [Google Scholar]

68. Porteus MH, Cathomen T, Weitzman MD, Baltimore D. Efficient gene targeting mediated by adeno-associated virus and DNA double-strand breaks. Mol Cell Biol. 2003;23(10):3558–3565. [PMC free article] [PubMed] [Google Scholar]

69. Vasileva A, Linden RM, Jessberger R. hom*ologous recombination is required for AAV-mediated gene targeting. Nucleic Acids Res. 2006;34(11):3345–3360. [PMC free article] [PubMed] [Google Scholar]
The reduction of the non-hom*ologous end-joining DNA-dependent protein kinase catalytic subunit by RNAi had no effect on gene targeting, while the reduction of hom*ologous recombination proteins RAD54B, RAD54L and XRCC3 decreased or eliminated vector targeting. These results demonstrate which hom*ologous recombination proteins are involved in targeting and a strategy for determining the cellular mechanisms involved.

70. Hurley PJ, Wilsker D, Bunz F. Human cancer cells require ATR for cell cycle progression following exposure to ionizing radiation. Oncogene. 2006;26(18):2535–2542. [PubMed] [Google Scholar]

71. Wang P, Yu J, Zhang L. The nuclear function of p53 is required for PUMA-mediated apoptosis induced by DNA damage. Proc Natl Acad Sci USA. 2007;104(10):4054–4059. [PMC free article] [PubMed] [Google Scholar]

72. Arena S, Isella C, Martini M, de Marco A, Medico E, Bardelli A. Knock-in of oncogenic Kras does not transform mouse somatic cells but triggers a transcriptional response that classifies human cancers. Cancer Res. 2007;67(18):8468–8476. [PubMed] [Google Scholar]

73. Samuels Y, Diaz LA, Jr, Schmidt-Kittler O, Cummins JM, DeLong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW, Vogelstein B, et al. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell. 2005;7(6):561–573. [PubMed] [Google Scholar]

74. Cummins JM, Rago C, Kohli M, Kinzler KW, Lengauer C, Vogelstein B. Tumour suppression: Disruption of HAUSP gene stabilizes p53. Nature. 2004;428(6982) [PubMed] [Google Scholar]
AAV vectors were used to knockout both alleles of the HAUSP gene in human cells by hom*ologous recombination. This study demonstrated that AAV-mediated gene targeting can be a powerful technique for human somatic cell genetics, and that double knockouts can be produced in human cells to determine gene function.

75. Kim JS, Lee C, Bonifant CL, Ressom H, Waldman T. Activation of p53-dependent growth suppression in human cells by mutations in PTEN or PIK3CA. Mol Cell Biol. 2007;27(2):662–677. [PMC free article] [PubMed] [Google Scholar]

76. Gallmeier E, Calhoun ES, Rago C, Brody JR, Cunningham SC, Hucl T, Gorospe M, Kohli M, Lengauer C, Kern SE. Targeted disruption of FANCC and FANCG in human cancer provides a preclinical model for specific therapeutic options. Gastroenterology. 2006;130(7):2145–2154. [PubMed] [Google Scholar]

77. Dang LH, Chen F, Ying C, Chun SY, Knock SA, Appelman HD, Dang DT. CDX2 has tumorigenic potential in the human colon cancer cell lines LOVO and SW48. Oncogene. 2005;25(15):2264–2272. [PubMed] [Google Scholar]

78. Dang DT, Chen F, Gardner LB, Cummins JM, Rago C, Bunz F, Kantsevoy SV, Dang LH. Hypoxia-inducible factor-1α promotes nonhypoxia-mediated proliferation in colon cancer cells and xenografts. Cancer Res. 2006;66(3):1684–1693. [PubMed] [Google Scholar]

79. Cunningham SC, Gallmeier E, Hucl T, Dezentje DA, Calhoun ES, Falco G, Abdelmohsen K, Gorospe M, Kern SE. Targeted deletion of MKK4 in cancer cells: A detrimental phenotype manifests as decreased experimental metastasis and suggests a counterweight to the evolution of tumor-suppressor loss. Cancer Res. 2006;66(11):5560–5564. [PubMed] [Google Scholar]

80. Dang DT, Chen F, Kohli M, Rago C, Cummins JM, Dang LH. Glutathione S-transferase π1 promotes tumorigenicity in HCT116 human colon cancer cells. Cancer Res. 2005;65(20):9485–9494. [PubMed] [Google Scholar]

81. Cummins JM, Kohli M, Rago C, Kinzler KW, Vogelstein B, Bunz F. X-linked inhibitor of apoptosis protein (XIAP) is a nonredundant modulator of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human cancer cells. Cancer Res. 2004;64(9):3006–3008. [PubMed] [Google Scholar]

82. Miller DG, Wang PR, Petek LM, Hirata RK, Sands MS, Russell DW. Gene targeting in vivo by adeno-associated virus vectors. Nat Biotechnol. 2006;24(8):1022–1026. [PubMed] [Google Scholar]

83. Wursthorn K, Storm T, Kay MA, Finegold M, Grompe M. In vivo correction of a metabolic liver disease by AAV8-mediated hom*ologous recombination. Mol Ther. 2006;13(Suppl 1) Abs 804. [Google Scholar]

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