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Genome Editing pp 125–137Cite as

Stimulation of AAV Gene Editing via DSB Repair

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB))

Abstract

Recent advancements in mammalian genome editing technologies have demonstrated precise genetic manipulations at the chromosomal level at efficiencies relevant for disease therapy. In fact, zinc-finger nucleases (ZFNs) that induce deletions in the HIV CCR5 receptor in patient T cells ex vivo have demonstrated promise upon treated cell infusion in the clinic. In these applications, adenoviral delivery vectors were employed however; there is growing popularity for the use of adeno-associated virus (AAV) gene delivery which has been used in over 100 clinical trials without any vector-related toxicity. This review chapter summarizes the development of AAV for clinical gene therapy, the early observations of AAV gene targeting, and the current status of AAV vectors for gene editing via site specific DNA double strand break repair. In addition, the remaining obstacles towards the combination of AAV vectorology and site-specific endonucleases for genetic engineering are discussed.

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References

  1. Atchison RW, Casto BC, Hammon WM. Adenovirus-associated defective virus particles. Science. 1965;149(3685):754–6.

    Article  CAS  PubMed  Google Scholar 

  2. Fields BN, Knipe DM, Howley PM. Ovid technologies Inc. Fields’ virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2007. Available from: http://eresources.lib.unc.edu/external_db/external_database_auth.html?A=P%7CF=N%7CID=162631%7CREL=HSL%7CSO=HSL%7CURL=http://libproxy.lib.unc.edu/login?url=http://gateway.ovid.com/ovidweb.cgi?T=JS&NEWS=N&PAGE=booktext&D=books&AN=00139921/5th_Edition/.

  3. Berns KI, Pinkerton TC, Thomas GF, Hoggan MD. Detection of adeno-associated virus (AAV)-specific nucleotide sequences in DNA isolated from latently infected Detroit 6 cells. Virology. 1975;68(2):556–60.

    Article  CAS  PubMed  Google Scholar 

  4. Xiao X, Xiao W, Li J, Samulski RJ. A novel 165-base-pair terminal repeat sequence is the sole cis requirement for the adeno-associated virus life cycle. J Virol. 1997;71(2):941–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. King JA, Dubielzig R, Grimm D, Kleinschmidt JA. DNA helicase-mediated packaging of adeno-associated virus type 2 genomes into preformed capsids. EMBO J. 2001;20(12):3282–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kyostio SR, Owens RA, Weitzman MD, Antoni BA, Chejanovsky N, Carter BJ. Analysis of adeno-associated virus (AAV) wild-type and mutant Rep proteins for their abilities to negatively regulate AAV p5 and p19 mRNA levels. J Virol. 1994;68(5):2947–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Sonntag F, Schmidt K. Kleinschmidt JrA. A viral assembly factor promotes AAV2 capsid formation in the nucleolus. Proc Natl Acad Sci. 2010;107(22):10220–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gao G, Vandenberghe LH, Alvira MR, Lu Y, Calcedo R, Zhou X, et al. Clades of adeno-associated viruses are widely disseminated in human tissues. J Virol. 2004;78(12):6381–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ellis B, Hirsch M, Barker J, Connelly J, Steininger R, Porteus M. A survey of ex vivo/in vitro transduction efficiency of mammalian primary cells and cell lines with Nine natural adeno-associated virus (AAV1-9) and one engineered adeno-associated virus serotype. Virol J. 2013;10(1):74. doi:10.1186/1743-422X-10-74.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zincarelli C, Soltys S, Rengo G, Rabinowitz JE. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther. 2008;16(6):1073–80.

    Article  CAS  PubMed  Google Scholar 

  11. Grieger JC, Choi VW, Samulski RJ. Production and characterization of adeno-associated viral vectors. Nat Protoc. 2006;1(3):1412–28. PubMed Epub 2007/04/05. eng.

    Article  CAS  PubMed  Google Scholar 

  12. Asokan A, Schaffer DV, Samulski RJ. The AAV vector toolkit: poised at the clinical crossroads. Mol Ther. 2012;20(4):699–708. PubMed Epub 2012/01/26. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bartlett JS, Wilcher R, Samulski RJ. Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors. J Virol. 2000;74(6):2777–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Xiao PJ, Samulski RJ. Cytoplasmic trafficking, endosomal escape, and perinuclear accumulation of adeno-associated virus type 2 particles are facilitated by microtubule network. J Virol. 2012;86(19):10462–73. PubMed Epub 2012/07/20. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Popa-Wagner R, Porwal M, Kann M, Reuss M, Weimer M, Florin L, et al. Impact of VP1-specific protein sequence motifs on adeno-associated virus type 2 intracellular trafficking and nuclear entry. J Virol. 2012;86(17):9163–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rabinowitz JE, Samulski RJ. Building a better vector: the manipulation of AAV virions. Virology. 2000;278(2):301–8.

    Article  CAS  PubMed  Google Scholar 

  17. Johnson JS, Samulski RJ. Enhancement of adeno-associated virus infection by mobilizing capsids into and out of the nucleolus. J Virol. 2009;83(6):2632–44. PubMed Pubmed Central PMCID: 2648275, Epub 2008/12/26. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ferrari FK, Samulski T, Shenk T, Samulski RJ. Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors. J Virol. 1996;70(5):3227–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Beaton A, Palumbo P, Berns KI. Expression from the adeno-associated virus p5 and p19 promoters is negatively regulated in trans by the rep protein. J Virol. 1989;63(10):4450–4. PubMed Epub 1989/10/01. eng.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Miao CH, Snyder RO, Schowalter DB, Patijn GA, Donahue B, Winther B, et al. The kinetics of rAAV integration in the liver. Nat Genet. 1998;19(1):13–5. PubMed Epub 1998/05/20. eng.

    Article  CAS  PubMed  Google Scholar 

  21. Cheung AK, Hoggan MD, Hauswirth WW, Berns KI. Integration of the adeno-associated virus genome into cellular DNA in latently infected human Detroit 6 cells. J Virol. 1980;33(2):739–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Hirsch ML, Storici F, Li C, Choi VW, Samulski RJ. AAV recombineering with single strand oligonucleotides. PLoS One. 2009;4(11), e7705. PubMed Pubmed Central PMCID: 2765622, Epub 2009/11/06. eng.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kotin RM, Siniscalco M, Samulski RJ, Zhu XD, Hunter L, Laughlin CA, et al. Site-specific integration by adeno-associated virus. Proc Natl Acad Sci U S A. 1990;87(6):2211–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Samulski RJ, Zhu X, Xiao X, Brook JD, Housman DE, Epstein N, et al. Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J. 1991;10(12):3941–50. PubMed Epub 1991/12/01. eng.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Deyle DR, Russell DW. Adeno-associated virus vector integration. Curr Opin Mol Ther. 2009;11(4):442–7. PubMed Epub 2009/08/04. eng.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. McCarty DM, Young Jr SM, Samulski RJ. Integration of adeno-associated virus (AAV) and recombinant AAV vectors. Annu Rev Genet. 2004;38:819–45. PubMed Epub 2004/12/01. eng.

    Article  CAS  PubMed  Google Scholar 

  27. Rosas LE, Grieves JL, Zaraspe K, La Perle KMD, Fu H, McCarty DM. Patterns of scAAV vector insertion associated with oncogenic events in a mouse model for genotoxicity. Mol Ther. 2012;20(11):2098–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 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):11434–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. McCarty DM, Monahan PE, Samulski RJ. Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis. Gene Ther. 2001;8(16):1248–54. PubMed Epub 2001/08/18. eng.

    Article  CAS  PubMed  Google Scholar 

  30. Wang Z, Ma HI, Li J, Sun L, Zhang J, Xiao X. Rapid and highly efficient transduction by double-stranded adeno-associated virus vectors in vitro and in vivo. Gene Ther. 2003;10(26):2105–11. PubMed Epub 2003/11/20. eng.

    Article  CAS  PubMed  Google Scholar 

  31. McCarty DM, Fu H, Monahan PE, Toulson CE, Naik P, Samulski RJ. Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo. Gene Ther. 2003;10(26):2112–8. PubMed Epub 2003/11/20. eng.

    Article  CAS  PubMed  Google Scholar 

  32. Hirsch ML, Green L, Porteus MH, Samulski RJ. Self-complementary AAV mediates gene targeting and enhances endonuclease delivery for double-strand break repair. Gene Ther. 2010;17(9):1175–80. PubMed Pubmed Central PMCID: 3152950, Epub 2010/05/14. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mueller C, Flotte TR. Clinical gene therapy using recombinant adeno-associated virus vectors. Gene Ther. 2008;15(11):858–63.

    Article  CAS  PubMed  Google Scholar 

  34. Podsakoff G, Wong KK, Chatterjee S. Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors. J Virol. 1994;68(9):5656–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Xiao X, Li J, Samulski RJ. Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J Virol. 1996;70(11):8098–108.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Rabinowitz JE, Bowles DE, Faust SM, Ledford JG, Cunningham SE, Samulski RJ. Cross-dressing the virion: the transcapsidation of adeno-associated virus serotypes functionally defines subgroups. J Virol. 2004;78(9):4421–32. PubMed Epub 2004/04/14. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rabinowitz JE, Rolling F, Li C, Conrath H, Xiao W, Xiao X, et al. Cross-packaging of a single adeno-associated virus (AAV) type 2 vector genome into multiple AAV serotypes enables transduction with broad specificity. J Virol. 2002;76(2):791–801. PubMed Epub 2001/12/26. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ellis BL, Hirsch ML, Barker JC, Connelly JP, Steininger 3rd RJ, Porteus MH. A survey of ex vivo/in vitro transduction efficiency of mammalian primary cells and cell lines with Nine natural adeno-associated virus (AAV1-9) and one engineered adeno-associated virus serotype. Virol J. 2013;10:74. PubMed Pubmed Central PMCID: 3607841.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Mitchell AM, Nicolson SC, Warischalk JK, Samulski RJ. AAV’s anatomy: roadmap for optimizing vectors for translational success. Curr Gene Ther. 2010;10(5):319–40. PubMed Epub 2010/08/18. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 2011;365(25):2357–65. PubMed Pubmed Central PMCID: 3265081, Epub 2011/12/14. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, 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):342–7. PubMed Epub 2006/02/14. eng.

    Article  CAS  PubMed  Google Scholar 

  42. Gray SJ. Gene therapy and neurodevelopmental disorders. Neuropharmacology. 2013;68:136–42. PubMed Epub 2012/07/04. eng.

    Article  CAS  PubMed  Google Scholar 

  43. Zouein FA, Booz GW. AAV-mediated gene therapy for heart failure: enhancing contractility and calcium handling. F1000Prime Rep. 2013;5:27. PubMed Epub 2013/08/24. eng.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Gaudet D, Methot J, Kastelein J. Gene therapy for lipoprotein lipase deficiency. Curr Opin Lipidol. 2012;23(4):310–20. PubMed Epub 2012/06/14. eng.

    Article  CAS  PubMed  Google Scholar 

  45. Carpentier AC, Frisch F, Labbe SM, Gagnon R, de Wal J, Greentree S, et al. Effect of alipogene tiparvovec (AAV1-LPL(S447X)) on postprandial chylomicron metabolism in lipoprotein lipase-deficient patients. J Clin Endocrinol Metab. 2012;97(5):1635–44. PubMed Epub 2012/03/23. eng.

    Article  CAS  PubMed  Google Scholar 

  46. Gaudet D, Methot J, Dery S, Brisson D, Essiembre C, Tremblay G, et al. Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial. Gene Ther. 2013;20(4):361–9. PubMed Epub 2012/06/22. eng.

    Article  CAS  PubMed  Google Scholar 

  47. Stroes ES, Nierman MC, Meulenberg JJ, Franssen R, Twisk J, Henny CP, et al. Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler Thromb Vasc Biol. 2008;28(12):2303–4. PubMed Epub 2008/09/20. eng.

    Article  CAS  PubMed  Google Scholar 

  48. Ali RR, Reichel MB, Thrasher AJ, Levinsky RJ, Kinnon C, Kanuga N, et al. Gene transfer into the mouse retina mediated by an adeno-associated viral vector. Hum Mol Genet. 1996;5(5):591–4. PubMed Epub 1996/05/01. eng.

    Article  CAS  PubMed  Google Scholar 

  49. Barker SE, Broderick CA, Robbie SJ, Duran Y, Natkunarajah M, Buch P, et al. Subretinal delivery of adeno-associated virus serotype 2 results in minimal immune responses that allow repeat vector administration in immunocompetent mice. J Gene Med. 2009;11(6):486–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Jacobson SG, Cideciyan AV, Ratnakaram R, Heon E, Schwartz SB, Roman AJ, et al. Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Arch Ophthalmol. 2012;130(1):9–24. PubMed Epub 2011/09/14. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. McClements ME, MacLaren RE. Gene therapy for retinal disease. Transl Res. 2013;161(4):241–54. PubMed Epub 2013/01/12. eng.

    Article  CAS  PubMed  Google Scholar 

  52. Testa F, Maguire AM, Rossi S, Pierce EA, Melillo P, Marshall K, et al. Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital Amaurosis type 2. Ophthalmology. 2013;120(6):1283–91. PubMed Pubmed Central PMCID: 3674112.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med. 2008;358(21):2231–9. PubMed Epub 2008/04/29. eng.

    Article  CAS  PubMed  Google Scholar 

  54. Hauswirth WW, Aleman TS, Kaushal S, Cideciyan AV, Schwartz SB, Wang L, et al. Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther. 2008;19(10):979–90. PubMed Epub 2008/09/09. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Maguire AM, High KA, Auricchio A, Wright JF, Pierce EA, Testa F, et al. Age-dependent effects of RPE65 gene therapy for Leber’s congenital amaurosis: a phase 1 dose-escalation trial. Lancet. 2009;374(9701):1597–605. PubMed Epub 2009/10/27. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Maguire AM, Simonelli F, Pierce EA, Pugh Jr EN, Mingozzi F, Bennicelli J, et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med. 2008;358(21):2240–8. PubMed Epub 2008/04/29. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Bennett J, Ashtari M, Wellman J, Marshall KA, Cyckowski LL, Chung DC, et al. AAV2 gene therapy readministration in three adults with congenital blindness. Sci Transl Med. 2012;4(120):120ra15.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Cai X, Conley SM, Naash MI. RPE65: role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet. 2009;30(2):57–62. PubMed Epub 2009/04/18. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Russell DW, Hirata RK. Human gene targeting by viral vectors. Nat Genet. 1998;18(4):325–30. PubMed Pubmed Central PMCID: 3010411, Epub 1998/04/16. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Russell DW, Hirata RK. Human gene targeting favors insertions over deletions. Hum Gene Ther. 2008;19(9):907–14. PubMed Pubmed Central PMCID: 2940567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hirata RK, Russell DW. Design and packaging of adeno-associated virus gene targeting vectors. J Virol. 2000;74(10):4612–20. PubMed Pubmed Central PMCID: 111981, Epub 2000/04/25. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Russell DW, Miller AD, Alexander IE. Adeno-associated virus vectors preferentially transduce cells in S phase. Proc Natl Acad Sci U S A. 1994;91(19):8915–9. PubMed Pubmed Central PMCID: 44717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Trobridge G, Hirata RK, Russell DW. Gene targeting by adeno-associated virus vectors is cell-cycle dependent. Hum Gene Ther. 2005;16(4):522–6. PubMed.

    Article  CAS  PubMed  Google Scholar 

  64. Liu X, Yan Z, Luo M, Zak R, Li Z, Driskell RR, et al. Targeted correction of single-base-pair mutations with adeno-associated virus vectors under nonselective conditions. J Virol. 2004;78(8):4165–75. PubMed Pubmed Central PMCID: 374254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Cervelli T, Palacios JA, Zentilin L, Mano M, Schwartz RA, Weitzman MD, et al. Processing of recombinant AAV genomes occurs in specific nuclear structures that overlap with foci of DNA-damage-response proteins. J Cell Sci. 2008;121(Pt 3):349–57. PubMed.

    Article  CAS  PubMed  Google Scholar 

  66. Inagaki K, Ma C, Storm TA, Kay MA, Nakai H. The role of DNA-PKcs and artemis in opening viral DNA hairpin termini in various tissues in mice. J Virol. 2007;81(20):11304–21. PubMed Pubmed Central PMCID: 2045570, Epub 2007/08/10. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Schwartz RA, Carson CT, Schuberth C, Weitzman MD. Adeno-associated virus replication induces a DNA damage response coordinated by DNA-dependent protein kinase. J Virol. 2009;83(12):6269–78. PubMed Pubmed Central PMCID: 2687378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Paulk NK, Loza LM, Finegold MJ, Grompe M. AAV-mediated gene targeting is significantly enhanced by transient inhibition of nonhomologous end joining or the proteasome in vivo. Hum Gene Ther. 2012;23(6):658–65. PubMed Pubmed Central PMCID: 3392621.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. 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):3550–7. PubMed Pubmed Central PMCID: 164770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Porteus MH, Baltimore D. Chimeric nucleases stimulate gene targeting in human cells. Science. 2003;300(5620):763. PubMed Epub 2003/05/06. eng.

    Article  PubMed  Google Scholar 

  71. Li H, Haurigot V, Doyon Y, Li T, Wong SY, Bhagwat AS, et al. In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature. 2011;475(7355):217–21. PubMed Pubmed Central PMCID: 3152293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Asuri P, Bartel MA, Vazin T, Jang JH, Wong TB, Schaffer DV. Directed evolution of adeno-associated virus for enhanced gene delivery and gene targeting in human pluripotent stem cells. Mol Ther. 2012;20(2):329–38. PubMed Pubmed Central PMCID: 3277219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Handel EM, Gellhaus K, Khan K, Bednarski C, Cornu TI, Muller-Lerch F, et al. Versatile and efficient genome editing in human cells by combining zinc-finger nucleases with adeno-associated viral vectors. Hum Gene Ther. 2012;23(3):321–9. PubMed Pubmed Central PMCID: 3300077.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Ellis BL, Hirsch ML, Porter SN, Samulski RJ, Porteus MH. Zinc-finger nuclease-mediated gene correction using single AAV vector transduction and enhancement by Food and Drug Administration-approved drugs. Gene Ther. 2013;20(1):35–42. PubMed Epub 2012/01/20. Eng.

    Article  CAS  PubMed  Google Scholar 

  75. Rahman SH, Bobis-Wozowicz S, Chatterjee D, Gellhaus K, Pars K, Heilbronn R, et al. The nontoxic cell cycle modulator indirubin augments transduction of adeno-associated viral vectors and zinc-finger nuclease-mediated gene targeting. Hum Gene Ther. 2013;24(1):67–77. PubMed Pubmed Central PMCID: 3555098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Anguela XM, Sharma R, Doyon Y, Miller JC, Li H, Haurigot V, et al. Robust ZFN-mediated genome editing in adult hemophilic mice. Blood. 2013;122(19):3283–7. PubMed Pubmed Central PMCID: 3821724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Beurdeley M, Bietz F, Li J, Thomas S, Stoddard T, Juillerat A, et al. Compact designer TALENs for efficient genome engineering. Nat Commun. 2013;4:1762. PubMed Pubmed Central PMCID: 3644105.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Esvelt KM, Mali P, Braff JL, Moosburner M, Yaung SJ, Church GM. Orthogonal Cas9 proteins for RNA-guided gene regulation and editing. Nat Methods. 2013;10(11):1116–21. PubMed Pubmed Central PMCID: 3844869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hirsch ML, Fagan BM, Dumitru R, Bower JJ, Yadav S, Porteus MH, et al. Viral single-strand DNA induces p53-dependent apoptosis in human embryonic stem cells. PLoS One. 2011;6(11), e27520. PubMed Pubmed Central PMCID: 3219675, Epub 2011/11/25. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Song L, Li X, Jayandharan GR, Wang Y, Aslanidi GV, Ling C, et al. High-efficiency transduction of primary human hematopoietic stem cells and erythroid lineage-restricted expression by optimized AAV6 serotype vectors in vitro and in a murine xenograft model in vivo. PLoS One. 2013;8(3), e58757. PubMed Pubmed Central PMCID: 3597592.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Maina N, Han Z, Li X, Hu Z, Zhong L, Bischof D, et al. Recombinant self-complementary adeno-associated virus serotype vector-mediated hematopoietic stem cell transduction and lineage-restricted, long-term transgene expression in a murine serial bone marrow transplantation model. Hum Gene Ther. 2008;19(4):376–83. PubMed.

    Article  CAS  PubMed  Google Scholar 

  82. Srivastava A. Hematopoietic stem cell transduction by recombinant adeno-associated virus vectors: problems and solutions. Hum Gene Ther. 2005;16(7):792–8. PubMed.

    Article  CAS  PubMed  Google Scholar 

  83. Duan D, Yue Y, Engelhardt JF. Expanding AAV packaging capacity with trans-splicing or overlapping vectors: a quantitative comparison. Mol Ther. 2001;4(4):383–91. PubMed Epub 2001/10/11. eng.

    Article  CAS  PubMed  Google Scholar 

  84. Hirsch ML, Agbandje-McKenna M, Samulski RJ. Little vector, big gene transduction: fragmented genome reassembly of adeno-associated virus. Mol Ther. 2010;18(1):6–8. PubMed Pubmed Central PMCID: 2839225, Epub 2010/01/06. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Hirsch ML, Li C, Bellon I, Yin C, Chavala S, Pryadkina M, et al. Oversized AAV transduction is mediated via a DNA-PKcs independent, Rad51C-dependent repair pathway. Mol Ther. 2013;13. PubMed.

    Google Scholar 

  86. Lai Y, Yue Y, Duan D. Evidence for the failure of adeno-associated virus serotype 5 to package a viral genome > or = 8.2 kb. Mol Ther. 2010;18(1):75–9. PubMed Pubmed Central PMCID: 2839223, Epub 2009/11/12. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Wu Z, Yang H, Colosi P. Effect of genome size on AAV vector packaging. Mol Ther. 2010;18(1):80–6. PubMed Pubmed Central PMCID: 2839202, Epub 2009/11/12. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Halbert CL, Allen JM, Miller AD. Efficient mouse airway transduction following recombination between AAV vectors carrying parts of a larger gene. Nat Biotechnol. 2002;20(7):697–701. PubMed Epub 2002/06/29. eng.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Angela M. Mitchell Ph.D. & Matthew Louis Hirsch Ph.D.

  2. Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Rachel Moser B.A. & Matthew Louis Hirsch Ph.D.

  3. Department of Pharmacology, Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Richard Jude Samulski Ph.D.

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  1. Angela M. Mitchell Ph.D.
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  3. Richard Jude Samulski Ph.D.
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  4. Matthew Louis Hirsch Ph.D.
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Corresponding author

Correspondence to Matthew Louis Hirsch Ph.D. .

Editor information

Editors and Affiliations

  1. Inst for Cell & Gene Therapy, Universitaetsklinikum Freiburg, Freiburg, Baden-Württemberg, Germany

    Toni Cathomen

  2. University of North Carolina, Chapel Hill, North Carolina, USA

    Matthew Hirsch

  3. Stanford Medical School, Palo Alto, California, USA

    Matthew Porteus

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© 2016 American Society of Gene and Cell Therapy

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Mitchell, A.M., Moser, R., Samulski, R.J., Hirsch, M.L. (2016). Stimulation of AAV Gene Editing via DSB Repair. In: Cathomen, T., Hirsch, M., Porteus, M. (eds) Genome Editing. Advances in Experimental Medicine and Biology(). Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3509-3_8

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