1932

Abstract

The ability to manipulate the genome with precise spatial and nucleotide resolution (genome editing) has been a powerful research tool. In the past decade, the tools and expertise for using genome editing in human somatic cells and pluripotent cells have increased to such an extent that the approach is now being developed widely as a strategy to treat human disease. The fundamental process depends on creating a site-specific DNA double-strand break (DSB) in the genome and then allowing the cell's endogenous DSB repair machinery to fix the break such that precise nucleotide changes are made to the DNA sequence. With the development and discovery of several different nuclease platforms and increasing knowledge of the parameters affecting different genome editing outcomes, genome editing frequencies now reach therapeutic relevance for a wide variety of diseases. Moreover, there is a series of complementary approaches to assessing the safety and toxicity of any genome editing process, irrespective of the underlying nuclease used. Finally, the development of genome editing has raised the issue of whether it should be used to engineer the human germline. Although such an approach could clearly prevent the birth of people with devastating and destructive genetic diseases, questions remain about whether human society is morally responsible enough to use this tool.

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2016-01-06
2024-04-13
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Literature Cited

  1. Carroll D. 1.  2014. Genome engineering with targetable nucleases. Annu. Rev. Biochem. 83:409–39 [Google Scholar]
  2. Russell DW, Hirata RK. 2.  1998. Human gene targeting by viral vectors. Nat. Genet. 18:325–30 [Google Scholar]
  3. Barzel A, Paulk NK, Shi Y, Huang Y, Chu K. 3.  et al. 2015. Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature 517:360–64 [Google Scholar]
  4. Szostak JW, Orr-Weaver TL, Rothstein RJ, Stahl FW. 4.  1983. The double-strand-break repair model for recombination. Cell 33:25–35 [Google Scholar]
  5. Orr-Weaver TL, Szostak JW, Rothstein RJ. 5.  1983. Genetic applications of yeast transformation with linear and gapped plasmids. Methods Enzymol. 101:228–45 [Google Scholar]
  6. Doetschman T, Gregg RG, Maeda N, Hooper ML, Melton DW. 6.  et al. 1987. Targetted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature 330:576–78 [Google Scholar]
  7. Doetschman T, Maeda N. 7.  , Smithies O. 1988. Targeted mutation of the Hprt gene in mouse embryonic stem cells. PNAS 85:8583–87 [Google Scholar]
  8. Thomas KR, Capecchi MR. 8.  1986. Introduction of homologous DNA sequences into mammalian cells induces mutations in the cognate gene. Nature 324:34–38 [Google Scholar]
  9. Thomas KR, Capecchi MR. 9.  1987. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:503–12 [Google Scholar]
  10. Mansour SL, Thomas KR, Capecchi MR. 10.  1988. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 336:348–52 [Google Scholar]
  11. Smithies O, Gregg RG, Boggs SS, Koralewski MA, Kucherlapati RS. 11.  1985. Insertion of DNA sequences into the human chromosomal β-globin locus by homologous recombination. Nature 317:230–34 [Google Scholar]
  12. Rouet P, Smih F, Jasin M. 12.  1994. Introduction of double-strand breaks into the genome of mouse cells by expression of rare-cutting endonuclease. Mol. Cell. Biol. 14:8096–106 [Google Scholar]
  13. Rouet P, Smih F, Jasin M. 13.  1994. Expression of a site-specific endonuclease stimulates homologous recombination in mammalian cells. PNAS 91:6064–68 [Google Scholar]
  14. Smih F, Rouet P, Romanienko PJ, Jasin M. 14.  1995. Double-strand breaks at the target locus stimulate gene targeting in embryonic stem cells. Nucleic Acids Res. 23:5012–19 [Google Scholar]
  15. Sargent RG, Brenneman MA, Wilson JH. 15.  1997. Repair of site-specific double-strand breaks in a mammalian chromosome by homologous and illegitimate recombination. Mol. Cell. Biol. 17:267–77 [Google Scholar]
  16. Taghian DG, Nickoloff JA. 16.  1997. Chromosomal double-strand breaks induce gene conversion at high frequency in mammalian cells. Mol. Cell. Biol. 17:6386–93 [Google Scholar]
  17. Choulika A, Perrin A, Dujon B, Nicolas J-F. 17.  1995. Induction of homologous recombination in mammalian chromosomes by using the I-SceI system of Saccharomyces cerevisiae. Mol. Cell. Biol. 15:1968–73 [Google Scholar]
  18. Porteus MH, Baltimore D. 18.  2003. Chimeric nucleases stimulate gene targeting in human cells. Science 300:763 [Google Scholar]
  19. Rudin N, Haber JE. 19.  1988. Efficient repair of HO-induced chromosomal breaks in Saccharomyces cerevisiae by recombination between flanking homologous sequences. Mol. Cell. Biol. 8:3918–28 [Google Scholar]
  20. Jasin M, Berg P. 20.  1988. Homologous integration in mammalian cells without target gene selection. Genes Dev. 2:1353–63 [Google Scholar]
  21. Kim YG, Chandrasegaran S. 21.  1994. Chimeric restriction endonuclease. PNAS 91:883–87 [Google Scholar]
  22. Kim YG, Cha J, Chandrasegaran S. 22.  1996. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. PNAS 93:1156–60 [Google Scholar]
  23. Smith J, Berg JM, Chandrasegaran S. 23.  1999. A detailed study of the substrate specificity of a chimeric restriction enzyme. Nucleic Acids Res. 27:674–81 [Google Scholar]
  24. Smith J, Bibikova M, Whitby FG, Reddy AR, Chandrasegaran S, Carroll D. 24.  2000. Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains. Nucleic Acids Res. 28:3361–69 [Google Scholar]
  25. Bibikova M, Carroll D, Segal DJ, Trautman JK, Smith J. 25.  et al. 2001. Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. Mol. Cell. Biol. 21:289–97 [Google Scholar]
  26. Bibikova M, Golic M, Golic KG, Carroll D. 26.  2002. Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-finger nucleases. Genetics 161:1169–75 [Google Scholar]
  27. Bibikova M, Beumer K, Trautman JK, Carroll D. 27.  2003. Enhancing gene targeting with designed zinc finger nucleases. Science 300:764 [Google Scholar]
  28. Porteus MH. 28.  2006. Mammalian gene targeting with designed zinc finger nucleases. Mol. Ther. 13:438–46 [Google Scholar]
  29. Porteus MH, Carroll D. 29.  2005. Gene targeting using zinc finger nucleases. Nat. Biotechnol. 23:967–73 [Google Scholar]
  30. Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM. 30.  et al. 2005. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435:646–51 [Google Scholar]
  31. Kanaar R, Hoeijmakers JH, van Gent DC. 31.  1998. Molecular mechanisms of DNA double strand break repair. Trends Cell Biol. 8:483–89 [Google Scholar]
  32. Paques F, Haber JE. 32.  1999. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 63:349–404 [Google Scholar]
  33. Khanna KK, Jackson SP. 33.  2001. DNA double-strand breaks: signaling, repair and the cancer connection. Nat. Genet. 27:247–54 [Google Scholar]
  34. West SC. 34.  2003. Molecular views of recombination proteins and their control. Nat. Rev. Mol. Cell Biol. 4:435–45 [Google Scholar]
  35. Porteus M. 35.  2011. Seeing the light: integrating genome engineering with double-strand break repair. Nat. Methods 8:628–30 [Google Scholar]
  36. Guirouilh-Barbat J, Huck S, Bertrand P, Pirzio L, Desmaze C. 36.  et al. 2004. Impact of the KU80 pathway on NHEJ-induced genome rearrangements in mammalian cells. Mol. Cell 14:611–23 [Google Scholar]
  37. Certo MT, Gwiazda KS, Kuhar R, Sather B, Curinga G. 37.  et al. 2012. Coupling endonucleases with DNA end-processing enzymes to drive gene disruption. Nat. Methods 9:973–75 [Google Scholar]
  38. Richardson C, Jasin M. 38.  2000. Frequent chromosomal translocations induced by DNA double-strand breaks. Nature 405:697–700 [Google Scholar]
  39. Lee HJ, Kim E, Kim JS. 39.  2010. Targeted chromosomal deletions in human cells using zinc finger nucleases. Genome Res. 20:81–89 [Google Scholar]
  40. Hendel A, Kildebeck EJ, Fine EJ, Clark JT, Punjya N. 40.  et al. 2014. Quantifying genome-editing outcomes at endogenous loci with SMRT sequencing. Cell Rep. 7:293–305 [Google Scholar]
  41. Voit RA, McMahon MA, Sawyer SL, Porteus MH. 41.  2013. Generation of an HIV resistant T-cell line by targeted “stacking” of restriction factors. Mol. Ther. 21:786–95 [Google Scholar]
  42. Moehle EA, Rock JM, Lee YL, Jouvenot Y, DeKelver RC. 42.  et al. 2007. Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases. PNAS 104:3055–60 [Google Scholar]
  43. Potts PR, Porteus MH, Yu H. 43.  2006. Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. EMBO J. 25:3377–88 [Google Scholar]
  44. Yu C, Liu Y, Ma T, Liu K, Xu S. 44.  et al. 2015. Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell Stem Cell 16:142–47 [Google Scholar]
  45. Maruyama T, Dougan SK, Truttmann MC, Bilate AM, Ingram JR, Ploegh HL. 45.  2015. Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nat. Biotechnol. 33:538–42 [Google Scholar]
  46. Certo MT, Ryu BY, Annis JE, Garibov M, Jarjour J. 46.  et al. 2011. Tracking genome engineering outcome at individual DNA breakpoints. Nat. Methods 8:671–76 [Google Scholar]
  47. Chu VT, Weber T, Wefers B, Wurst W, Sander S. 47.  et al. 2015. Increasing the efficiency of homology-directed repair for CRISPR-Cas9-induced precise gene editing in mammalian cells. Nat. Biotechnol. 33:543–48 [Google Scholar]
  48. Lim DS, Hasty P. 48.  1996. A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53. Mol. Cell. Biol. 16:7133–43 [Google Scholar]
  49. Fattah FJ, Lichter NF, Fattah KR, Oh S, Hendrickson EA. 49.  2008. Ku70, an essential gene, modulates the frequency of rAAV-mediated gene targeting in human somatic cells. PNAS 105:8703–8 [Google Scholar]
  50. Silva G, Poirot L, Galetto R, Smith J, Montoya G. 50.  et al. 2011. Meganucleases and other tools for targeted genome engineering: perspectives and challenges for gene therapy. Curr. Gene Ther. 11:11–27 [Google Scholar]
  51. Jurica MS, Stoddard BL. 51.  1999. Homing endonucleases: structure, function and evolution. Cell. Mol. Life Sci. 55:1304–26 [Google Scholar]
  52. Chevalier BS, Kortemme T, Chadsey MS, Baker D, Monnat RJ, Stoddard BL. 52.  2002. Design, activity, and structure of a highly specific artificial endonuclease. Mol. Cell 10:895–905 [Google Scholar]
  53. Volná P, Jarjour J, Baxter S, Roffler SR, Monnat RJ Jr. 53.  2007. Flow cytometric analysis of DNA binding and cleavage by cell surface-displayed homing endonucleases. Nucleic Acids Res. 35:2748–58 [Google Scholar]
  54. Jarjour J, West-Foyle H, Certo MT, Hubert CG, Doyle L. 54.  et al. 2009. High-resolution profiling of homing endonuclease binding and catalytic specificity using yeast surface display. Nucleic Acids Res. 37:6871–80 [Google Scholar]
  55. Thyme SB, Jarjour J, Takeuchi R, Havranek JJ, Ashworth J. 55.  et al. 2009. Exploitation of binding energy for catalysis and design. Nature 461:1300–4 [Google Scholar]
  56. Epinat JC, Arnould S, Chames P, Rochaix P, Desfontaines D. 56.  et al. 2003. A novel engineered meganuclease induces homologous recombination in yeast and mammalian cells. Nucleic Acids Res. 31:2952–62 [Google Scholar]
  57. Segal DJ, Barbas CF III. 57.  2001. Custom DNA-binding proteins come of age: polydactyl zinc-finger proteins. Curr. Opin. Biotechnol. 12:632–37 [Google Scholar]
  58. Beerli RR, Barbas CF III. 58.  2002. Engineering polydactyl zinc-finger transcription factors. Nat. Biotechnol. 20:135–41 [Google Scholar]
  59. Liu Q, Xia Z, Zhong X, Case CC. 59.  2002. Validated zinc finger protein designs for all 16 GNN DNA triplet targets. J. Biol. Chem. 277:3850–56 [Google Scholar]
  60. Greisman HA, Pabo CO. 60.  1997. A general strategy for selecting high-affinity zinc finger proteins for diverse DNA target sites. Science 275:657–61 [Google Scholar]
  61. Rebar EJ, Pabo CO. 61.  1994. Zinc finger phage: affinity selection of fingers with new DNA-binding specificities. Science 263:671–73 [Google Scholar]
  62. Pruett-Miller SM, Connelly JP, Maeder ML, Joung JK, Porteus MH. 62.  2008. Comparison of zinc finger nucleases for use in gene targeting in mammalian cells. Mol. Ther. 16:707–17 [Google Scholar]
  63. Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM. 63.  et al. 2008. Rapid “open-source” engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol. Cell 31:294–301 [Google Scholar]
  64. Meng X, Brodsky MH, Wolfe SA. 64.  2005. A bacterial one-hybrid system for determining the DNA-binding specificity of transcription factors. Nat. Biotechnol. 23:988–94 [Google Scholar]
  65. Persikov AV, Wetzel JL, Rowland EF, Oakes BL, Xu DJ. 65.  et al. 2015. A systematic survey of the Cys2His2 zinc finger DNA-binding landscape. Nucleic Acids Res. 43:1965–84 [Google Scholar]
  66. Persikov AV, Rowland EF, Oakes BL, Singh M, Noyes MB. 66.  2014. Deep sequencing of large library selections allows computational discovery of diverse sets of zinc fingers that bind common targets. Nucleic Acids Res. 42:1497–508 [Google Scholar]
  67. Isalan M, Klug A, Choo Y. 67.  2001. A rapid, generally applicable method to engineer zinc fingers illustrated by targeting the HIV-1 promoter. Nat. Biotechnol. 19:656–60 [Google Scholar]
  68. Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA. 68.  et al. 2008. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat. Biotechnol. 26:808–16 [Google Scholar]
  69. Christian M, Cermak T, Doyle EL, Schmidt C, Zhang F. 69.  et al. 2010. Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 186:757–61 [Google Scholar]
  70. Cermak T, Doyle EL, Christian M, Wang L, Zhang Y. 70.  et al. 2011. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res. 39:e82 [Google Scholar]
  71. Bogdanove AJ, Voytas DF. 71.  2011. TAL effectors: customizable proteins for DNA targeting. Science 333:1843–46 [Google Scholar]
  72. Miller JC, Tan S, Qiao G, Barlow KA, Wang J. 72.  et al. 2011. A TALE nuclease architecture for efficient genome editing. Nat. Biotechnol. 29:143–48 [Google Scholar]
  73. Joung JK, Sander JD. 73.  2013. TALENs: a widely applicable technology for targeted genome editing. Nat. Rev. Mol. Cell Biol. 14:49–55 [Google Scholar]
  74. Boch J, Scholze H, Schornack S, Landgraf A, Hahn S. 74.  et al. 2009. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326:1509–12 [Google Scholar]
  75. Moscou MJ, Bogdanove AJ. 75.  2009. A simple cipher governs DNA recognition by TAL effectors. Science 326:1501 [Google Scholar]
  76. Miller JC, Zhang L, Xia DF, Campo JJ, Ankoudinova IV. 76.  et al. 2015. Improved specificity of TALE-based genome editing using an expanded RVD repertoire. Nat. Methods 12:465–71 [Google Scholar]
  77. Reyon D, Tsai SQ, Khayter C, Foden JA, Sander JD, Joung JK. 77.  2012. FLASH assembly of TALENs for high-throughput genome editing. Nat. Biotechnol. 30:460–65 [Google Scholar]
  78. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 78.  2012. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–21 [Google Scholar]
  79. Doudna JA, Charpentier E. 79.  2014. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346:1258096 [Google Scholar]
  80. Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y. 80.  et al. 2011. CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 471:602–7 [Google Scholar]
  81. Charpentier E. 81.  2015. CRISPR-Cas9: how research on a bacterial RNA-guided mechanism opened new perspectives in biotechnology and biomedicine. EMBO Mol. Med. 7:363–65 [Google Scholar]
  82. Mali P, Yang L, Esvelt KM, Aach J, Guell M. 82.  et al. 2013. RNA-guided human genome engineering via Cas9. Science 339:823–26 [Google Scholar]
  83. Cong L, Ran FA, Cox D, Lin S, Barretto R. 83.  et al. 2013. Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–23 [Google Scholar]
  84. Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS. 84.  et al. 2015. In vivo genome editing using Staphylococcus aureus Cas9. Nature 520:186–91 [Google Scholar]
  85. Esvelt KM, Mali P, Braff JL, Moosburner M, Yaung SJ, Church GM. 85.  2013. Orthogonal Cas9 proteins for RNA-guided gene regulation and editing. Nat. Methods 10:1116–21 [Google Scholar]
  86. Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT. 86.  et al. 2015. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523:481–85 [Google Scholar]
  87. Ramirez CL, Certo MT, Mussolino C, Goodwin MJ, Cradick TJ. 87.  et al. 2012. Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects. Nucleic Acids Res. 40:5560–68 [Google Scholar]
  88. Davis L, Maizels N. 88.  2014. Homology-directed repair of DNA nicks via pathways distinct from canonical double-strand break repair. PNAS 111:E924–32 [Google Scholar]
  89. Mali P, Aach J, Stranges PB, Esvelt KM, Moosburner M. 89.  et al. 2013. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat. Biotechnol. 31:833–38 [Google Scholar]
  90. Ran FA, Hsu PD, Lin CY, Gootenberg JS, Konermann S. 90.  et al. 2013. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154:1380–89 [Google Scholar]
  91. Boissel S, Jarjour J, Astrakhan A, Adey A, Gouble A. 91.  et al. 2014. MegaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering. Nucleic Acids Res. 42:2591–601 [Google Scholar]
  92. Tsai SQ, Wyvekens N, Khayter C, Foden JA, Thapar V. 92.  et al. 2014. Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat. Biotechnol. 32:569–76 [Google Scholar]
  93. Guilinger JP, Thompson DB, Liu DR. 93.  2014. Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat. Biotechnol. 32:577–82 [Google Scholar]
  94. Hendel A, Bak RO, Clark JT, Kennedy AB, Ryan DE. 94.  et al. 2015. Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells. Nat. Biotechnol. 33:985–89 [Google Scholar]
  95. Genovese P, Schiroli G, Escobar G, Di Tomaso T, Firrito C. 95.  et al. 2014. Targeted genome editing in human repopulating haematopoietic stem cells. Nature 510:235–40 [Google Scholar]
  96. Mock U, Machowicz R, Hauber I, Horn S, Abramowski P. 96.  et al. 2015. mRNA transfection of a novel TAL effector nuclease (TALEN) facilitates efficient knockout of HIV co-receptor CCR5. Nucleic Acids Res. 43:5560–71 [Google Scholar]
  97. Doyon Y, Choi VM, Xia DF, Vo TD, Gregory PD, Holmes MC. 97.  2010. Transient cold shock enhances zinc-finger nuclease-mediated gene disruption. Nat. Methods 7:459–60 [Google Scholar]
  98. Voit RA, Hendel A, Pruett-Miller SM, Porteus MH. 98.  2014. Nuclease-mediated gene editing by homologous recombination of the human globin locus. Nucleic Acids Res. 42:1365–78 [Google Scholar]
  99. Sargent RG, Suzuki S, Gruenert DC. 99.  2014. Nuclease-mediated double-strand break (DSB) enhancement of small fragment homologous recombination (SFHR) gene modification in human-induced pluripotent stem cells (hiPSCs). Methods Mol. Biol. 1114:279–90 [Google Scholar]
  100. Lombardo A, Genovese P, Beausejour CM, Colleoni S, Lee YL. 100.  et al. 2007. Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat. Biotechnol. 25:1298–306 [Google Scholar]
  101. Porteus MH, Cathomen T, Weitzman MD, Baltimore D. 101.  2003. Efficient gene targeting mediated by adeno-associated virus and DNA double-strand breaks. Mol. Cell. Biol. 23:3558–65 [Google Scholar]
  102. Miller DG, Petek LM, Russell DW. 102.  2003. Human gene targeting by adeno-associated virus vectors is enhanced by DNA double-strand breaks. Mol. Cell. Biol. 23:3550–57 [Google Scholar]
  103. Ellis BL, Hirsch ML, Porter SN, Samulski RJ, Porteus MH. 103.  2013. Zinc-finger nuclease-mediated gene correction using single AAV vector transduction and enhancement by Food and Drug Administration-approved drugs. Gene Ther. 20:35–42 [Google Scholar]
  104. Hirsch ML, Green L, Porteus MH, Samulski RJ. 104.  2010. Self-complementary AAV mediates gene targeting and enhances endonuclease delivery for double-strand break repair. Gene Ther. 17:1175–80 [Google Scholar]
  105. Yin H, Xue W, Chen S, Bogorad RL, Benedetti E. 105.  et al. 2014. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat. Biotechnol. 32:551–53 [Google Scholar]
  106. Chen F, Pruett-Miller SM, Huang Y, Gjoka M, Duda K. 106.  et al. 2011. High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases. Nat. Methods 8:753–55 [Google Scholar]
  107. Papaioannou I, Simons JP, Owen JS. 107.  2012. Oligonucleotide-directed gene-editing technology: mechanisms and future prospects. Expert Opin. Biol. Ther. 12:329–42 [Google Scholar]
  108. Maggio I, Gonçalves MA. 108.  2015. Genome editing at the crossroads of delivery, specificity, and fidelity. Trends Biotechnol. 33:280–91 [Google Scholar]
  109. Holt N, Wang J, Kim K, Friedman G, Wang X. 109.  et al. 2010. Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat. Biotechnol. 28:839–47 [Google Scholar]
  110. Tebas P, Stein D, Tang WW, Frank I, Wang SQ. 110.  et al. 2014. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J. Med. 370:901–10 [Google Scholar]
  111. Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A. 111.  et al. 2009. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N. Engl. J. Med. 360:692–98 [Google Scholar]
  112. Cradick TJ, Fine EJ, Antico CJ, Bao G. 112.  2013. CRISPR/Cas9 systems targeting β-globin and CCR5 genes have substantial off-target activity. Nucleic Acids Res. 41:9584–92 [Google Scholar]
  113. Mandal PK, Ferreira LM, Collins R, Meissner TB, Boutwell CL. 113.  et al. 2014. Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9. Cell Stem Cell 15:643–52 [Google Scholar]
  114. Mussolino C, Morbitzer R, Lütge F, Dannemann N, Lahaye T, Cathomen T. 114.  2011. A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res. 39:9283–93 [Google Scholar]
  115. Berdien B, Mock U, Atanackovic D, Fehse B. 115.  2014. TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer. Gene Ther. 21:539–48 [Google Scholar]
  116. Provasi E, Genovese P, Lombardo A, Magnani Z, Liu PQ. 116.  et al. 2012. Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat. Med. 18:807–15 [Google Scholar]
  117. Torikai H, Reik A, Liu PQ, Zhou Y, Zhang L. 117.  et al. 2012. A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR. Blood 119:5697–705 [Google Scholar]
  118. Ding Q, Strong A, Patel KM, Ng SL, Gosis BS. 118.  et al. 2014. Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ. Res. 115:488–92 [Google Scholar]
  119. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. 119.  2005. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat. Genet. 37:161–65 [Google Scholar]
  120. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. 120.  2006. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354:1264–72 [Google Scholar]
  121. Zhao Z, Tuakli-Wosornu Y, Lagace TA, Kinch L, Grishin NV. 121.  et al. 2006. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am. J. Hum. Genet. 79:514–23 [Google Scholar]
  122. Cradick TJ, Keck K, Bradshaw S, Jamieson AC, McCaffrey AP. 122.  2010. Zinc-finger nucleases as a novel therapeutic strategy for targeting hepatitis B virus DNAs. Mol. Ther. 18:947–54 [Google Scholar]
  123. Schiffer JT, Aubert M, Weber ND, Mintzer E, Stone D, Jerome KR. 123.  2012. Targeted DNA mutagenesis for the cure of chronic viral infections. J. Virol. 86:8920–36 [Google Scholar]
  124. Saayman S, Ali SA, Morris KV, Weinberg MS. 124.  2015. The therapeutic application of CRISPR/Cas9 technologies for HIV. Expert Opin. Biol. Ther. 15:819–30 [Google Scholar]
  125. Liao HK, Gu Y, Diaz A, Marlett J, Takahashi Y. 125.  et al. 2015. Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells. Nat. Commun. 6:6413 [Google Scholar]
  126. Ousterout DG, Perez-Pinera P, Thakore PI, Kabadi AM, Brown MT. 126.  et al. 2013. Reading frame correction by targeted genome editing restores dystrophin expression in cells from Duchenne muscular dystrophy patients. Mol. Ther. 21:1718–26 [Google Scholar]
  127. Ousterout DG, Kabadi AM, Thakore PI, Majoros WH, Reddy TE, Gersbach CA. 127.  2015. Multiplex CRISPR/Cas9-based genome editing for correction of dystrophin mutations that cause Duchenne muscular dystrophy. Nat. Commun. 6:6244 [Google Scholar]
  128. Ousterout DG, Kabadi AM, Thakore PI, Perez-Pinera P, Brown MT. 128.  et al. 2015. Correction of dystrophin expression in cells from Duchenne muscular dystrophy patients through genomic excision of exon 51 by zinc finger nucleases. Mol. Ther. 23:523–32 [Google Scholar]
  129. Li Y, Polak U, Bhalla AD, Rozwadowska N, Butler JS. 129.  et al. 2015. Excision of expanded GAA repeats alleviates the molecular phenotype of Friedreich's ataxia. Mol. Ther. 23:1055–65 [Google Scholar]
  130. Bauer DE, Kamran SC, Lessard S, Xu J, Fujiwara Y. 130.  et al. 2013. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 342:253–57 [Google Scholar]
  131. Lee HJ, Kweon J, Kim E, Kim S, Kim JS. 131.  2012. Targeted chromosomal duplications and inversions in the human genome using zinc finger nucleases. Genome Res. 22:539–48 [Google Scholar]
  132. Park CY, Kim J, Kweon J, Son JS, Lee JS. 132.  et al. 2014. Targeted inversion and reversion of the blood coagulation factor 8 gene in human iPS cells using TALENs. PNAS 111:9253–58 [Google Scholar]
  133. Johnston JJ, Lewis KL, Ng D, Singh LN, Wynter J. 133.  et al. 2015. Individualized iterative phenotyping for genome-wide analysis of loss-of-function mutations. Am. J. Hum. Genet. 96:913–25 [Google Scholar]
  134. Sulem P, Helgason H, Oddson A, Stefansson H, Gudjonsson SA. 134.  et al. 2015. Identification of a large set of rare complete human knockouts. Nat. Genet. 47:448–52 [Google Scholar]
  135. Kildebeck E, Checketts J, Porteus M. 135.  2012. Gene therapy for primary immunodeficiencies. Curr. Opin. Pediatr. 24:731–38 [Google Scholar]
  136. Gaziev J, Lucarelli G. 136.  2010. Allogeneic cellular gene therapy for hemoglobinopathies. Hematol./Oncol. Clin. North Am. 24:1145–63 [Google Scholar]
  137. Zou J, Mali P, Huang X, Dowey SN, Cheng L. 137.  2011. Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease. Blood 118:4599–608 [Google Scholar]
  138. Sebastiano V, Maeder ML, Angstman JF, Haddad B, Khayter C. 138.  et al. 2011. In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases. Stem Cells 29:1717–26 [Google Scholar]
  139. Osborn MJ, Gabriel R, Webber BR, DeFeo AP, McElroy AN. 139.  et al. 2015. Fanconi anemia gene editing by the CRISPR/Cas9 system. Hum. Gene Ther. 26:114–26 [Google Scholar]
  140. Osborn MJ, Starker CG, McElroy AN, Webber BR, Riddle MJ. 140.  et al. 2013. TALEN-based gene correction for epidermolysis bullosa. Mol. Ther. 21:1151–59 [Google Scholar]
  141. Flynn R, Grundmann A, Renz P, Haenseler W, James WS. 141.  et al. 2015. CRISPR-mediated genotypic and phenotypic correction of a chronic granulomatous disease mutation in human iPS cells. Exp. Hematol. 43:10838–48 [Google Scholar]
  142. Dupuy A, Valton J, Leduc S, Armier J, Galetto R. 142.  et al. 2013. Targeted gene therapy of xeroderma pigmentosum cells using meganuclease and TALEN. PLOS ONE 8:e78678 [Google Scholar]
  143. Ma N, Liao B, Zhang H, Wang L, Shan Y. 143.  et al. 2013. Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free β-thalassemia induced pluripotent stem cells. J. Biol. Chem. 288:34671–79 [Google Scholar]
  144. Popplewell L, Koo T, Leclerc X, Duclert A, Mamchaoui K. 144.  et al. 2013. Gene correction of a Duchenne muscular dystrophy mutation by meganuclease-enhanced exon knock-in. Hum. Gene Ther. 24:692–701 [Google Scholar]
  145. Papapetrou EP, Lee G, Malani N, Setty M, Riviere I. 145.  et al. 2011. Genomic safe harbors permit high β-globin transgene expression in thalassemia induced pluripotent stem cells. Nat. Biotechnol. 29:73–78 [Google Scholar]
  146. DeKelver RC, Choi VM, Moehle EA, Paschon DE, Hockemeyer D. 146.  et al. 2010. Functional genomics, proteomics, and regulatory DNA analysis in isogenic settings using zinc finger nuclease-driven transgenesis into a safe harbor locus in the human genome. Genome Res. 20:1133–42 [Google Scholar]
  147. Lombardo A, Cesana D, Genovese P, Di Stefano B, Provasi E. 147.  et al. 2011. Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat. Methods 8:861–69 [Google Scholar]
  148. Sadelain M, Papapetrou EP, Bushman FD. 148.  2012. Safe harbours for the integration of new DNA in the human genome. Nat. Rev. Cancer 12:51–58 [Google Scholar]
  149. Coluccio A, Miselli F, Lombardo A, Marconi A, Malagoli Tagliazucchi G. 149.  et al. 2013. Targeted gene addition in human epithelial stem cells by zinc-finger nuclease-mediated homologous recombination. Mol. Ther. 21:1695–704 [Google Scholar]
  150. Chang CJ, Bouhassira EE. 150.  2012. Zinc-finger nuclease-mediated correction of α-thalassemia in iPS cells. Blood 120:3906–14 [Google Scholar]
  151. Zou J, Sweeney CL, Chou BK, Choi U, Pan J. 151.  et al. 2011. Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease–mediated safe harbor targeting. Blood 117:5561–72 [Google Scholar]
  152. Merling RK, Sweeney CL, Chu J, Bodansky A, Choi U. 152.  et al. 2015. An AAVS1-targeted minigene platform for correction of iPSCs from all five types of chronic granulomatous disease. Mol. Ther. 23:147–57 [Google Scholar]
  153. Benabdallah BF, Allard E, Yao S, Friedman G, Gregory PD. 153.  et al. 2010. Targeted gene addition to human mesenchymal stromal cells as a cell-based plasma-soluble protein delivery platform. Cytotherapy 12:394–99 [Google Scholar]
  154. Barker JC, Barker AD, Bills J, Huang J, Wight-Carter M. 154.  et al. 2014. Genome editing of mouse fibroblasts by homologous recombination for sustained secretion of PDGF-B and augmentation of wound healing. Plast. Reconstr. Surg. 134:389e–401e [Google Scholar]
  155. Beard BC, Trobridge GD, Ironside C, McCune JS, Adair JE, Kiem HP. 155.  2010. Efficient and stable MGMT-mediated selection of long-term repopulating stem cells in nonhuman primates. J. Clin. Investig. 120:2345–54 [Google Scholar]
  156. Bonini C, Grez M, Traversari C, Ciceri F, Marktel S. 156.  et al. 2003. Safety of retroviral gene marking with a truncated NGF receptor. Nat. Med. 9:367–69 [Google Scholar]
  157. Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A. 157.  et al. 2011. Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl. J. Med. 365:1673–83 [Google Scholar]
  158. Zhou X, Dotti G, Krance RA, Martinez CA, Naik S. 158.  et al. 2015. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood 125:4103–13 [Google Scholar]
  159. Vogler I, Newrzela S, Hartmann S, Schneider N, von Laer D. 159.  et al. 2010. An improved bicistronic CD20/tCD34 vector for efficient purification and in vivo depletion of gene-modified T cells for adoptive immunotherapy. Mol. Ther. 18:1330–38 [Google Scholar]
  160. Wang X, Chang WC, Wong CW, Colcher D, Sherman M. 160.  et al. 2011. A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood 118:1255–63 [Google Scholar]
  161. Anguela XM, Sharma R, Doyon Y, Miller JC, Li H. 161.  et al. 2013. Robust ZFN-mediated genome editing in adult hemophilic mice. Blood 122:3283–87 [Google Scholar]
  162. Li H, Haurigot V, Doyon Y, Li T, Wong SY. 162.  et al. 2011. In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature 475:217–21 [Google Scholar]
  163. Cheng LT, Sun LT, Tada T. 163.  2012. Genome editing in induced pluripotent stem cells. Genes Cells 17:431–38 [Google Scholar]
  164. Sebastiano V, Zhen HH, Haddad B, Bashkirova E, Melo SP. 164.  et al. 2014. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Sci. Transl. Med. 6:264ra163 [Google Scholar]
  165. Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A. 165.  et al. 2007. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318:1920–23 [Google Scholar]
  166. Bousso P, Wahn V, Douagi I, Horneff G, Pannetier C. 166.  et al. 2000. Diversity, functionality, and stability of the T cell repertoire derived in vivo from a single human T cell precursor. PNAS 97:274–78 [Google Scholar]
  167. Weinstock DM, Richardson CA, Elliott B, Jasin M. 167.  2006. Modeling oncogenic translocations: distinct roles for double-strand break repair pathways in translocation formation in mammalian cells. DNA Repair. 5:1065–74 [Google Scholar]
  168. Pierce AJ, Stark JM, Araujo FD, Moynahan ME, Berwick M, Jasin M. 168.  2001. Double-strand breaks and tumorigenesis. Trends Cell Biol. 11:S52–59 [Google Scholar]
  169. Corrigan-Curay J, O'Reilly M, Kohn DB, Cannon PM, Bao G. 169.  et al. 2015. Genome editing technologies: defining a path to clinic. Mol. Ther. 23:796–806 [Google Scholar]
  170. Hendel A, Fine EJ, Bao G, Porteus MH. 170.  2015. Quantifying on- and off-target genome editing. Trends Biotechnol. 33:132–40 [Google Scholar]
  171. Cradick TJ, Qiu P, Lee CM, Fine EJ, Bao G. 171.  2014. COSMID: a web-based tool for identifying and validating CRISPR/Cas off-target sites. Mol. Ther. Nucleic Acids 3:e214 [Google Scholar]
  172. Fine EJ, Cradick TJ, Zhao CL, Lin Y, Bao G. 172.  2014. An online bioinformatics tool predicts zinc finger and TALE nuclease off-target cleavage. Nucleic Acids Res. 42:e42 [Google Scholar]
  173. Pattanayak V, Guilinger JP, Liu DR. 173.  2014. Determining the specificities of TALENs, Cas9, and other genome-editing enzymes. Methods Enzymol. 546:47–78 [Google Scholar]
  174. Pattanayak V, Ramirez CL, Joung JK, Liu DR. 174.  2011. Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection. Nat. Methods 8:765–70 [Google Scholar]
  175. Guilinger JP, Pattanayak V, Reyon D, Tsai SQ, Sander JD. 175.  et al. 2014. Broad specificity profiling of TALENs results in engineered nucleases with improved DNA-cleavage specificity. Nat. Methods 11:429–35 [Google Scholar]
  176. Pattanayak V, Lin S, Guilinger JP, Ma E, Doudna JA, Liu DR. 176.  2013. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat. Biotechnol. 31:839–43 [Google Scholar]
  177. Lin Y, Waldman AS. 177.  2001. Capture of DNA sequences at double-strand breaks in mammalian chromosomes. Genetics 158:1665–74 [Google Scholar]
  178. Lin Y, Waldman AS. 178.  2001. Promiscuous patching of broken chromosomes in mammalian cells with extrachromosomal DNA. Nucleic Acids Res. 29:3975–81 [Google Scholar]
  179. Miller DG, Petek LM, Russell DW. 179.  2004. Adeno-associated virus vectors integrate at chromosome breakage sites. Nat. Genet. 36:767–73 [Google Scholar]
  180. Gabriel R, Lombardo A, Arens A, Miller JC, Genovese P. 180.  et al. 2011. An unbiased genome-wide analysis of zinc-finger nuclease specificity. Nat. Biotechnol. 29:816–23 [Google Scholar]
  181. Tsai SQ, Zheng Z, Nguyen NT, Liebers M, Topkar VV. 181.  et al. 2014. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat. Biotechnol. 33:187–97 [Google Scholar]
  182. Chiarle R, Zhang Y, Frock RL, Lewis SM, Molinie B. 182.  et al. 2011. Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 147:107–19 [Google Scholar]
  183. Frock RL, Hu J, Meyers RM, Ho YJ, Kii E, Alt FW. 183.  2015. Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases. Nat. Biotechnol. 33:179–86 [Google Scholar]
  184. Miller JC, Holmes MC, Wang J, Guschin DY, Lee YL. 184.  et al. 2007. An improved zinc-finger nuclease architecture for highly specific genome editing. Nat. Biotechnol. 25:778–85 [Google Scholar]
  185. Pruett-Miller SM, Reading DW, Porter SN, Porteus MH. 185.  2009. Attenuation of zinc finger nuclease toxicity by small-molecule regulation of protein levels. PLOS Genet. 5:e1000376 [Google Scholar]
  186. Doyon Y, Vo TD, Mendel MC, Greenberg SG, Wang J. 186.  et al. 2011. Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nat. Methods 8:74–79 [Google Scholar]
  187. Szczepek M, Brondani V, Buchel J, Serrano L, Segal DJ, Cathomen T. 187.  2007. Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases. Nat. Biotechnol. 25:786–93 [Google Scholar]
  188. Dewey FE, Grove ME, Pan C, Goldstein BA, Bernstein JA. 188.  et al. 2014. Clinical interpretation and implications of whole-genome sequencing. JAMA 311:1035–45 [Google Scholar]
  189. Tomasetti C, Vogelstein B. 189.  2015. Cancer risk: role of environment—response. Science 347:729–31 [Google Scholar]
  190. Tomasetti C, Vogelstein B. 190.  2015. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347:78–81 [Google Scholar]
  191. Mussolino C, Alzubi J, Fine EJ, Morbitzer R, Cradick TJ. 191.  et al. 2014. TALENs facilitate targeted genome editing in human cells with high specificity and low cytotoxicity. Nucleic Acids Res. 42:6762–73 [Google Scholar]
  192. Porter SN, Baker LC, Mittelman D, Porteus MH. 192.  2014. Lentiviral and targeted cellular barcoding reveals ongoing clonal dynamics of cell lines in vitro and in vivo. Genome Biol. 15:R75 [Google Scholar]
  193. Li L, Krymskaya L, Wang J, Henley J, Rao A. 193.  et al. 2013. Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases. Mol. Ther. 21:1259–69 [Google Scholar]
  194. Liang P, Xu Y, Zhang X, Ding C, Huang R. 194.  et al. 2015. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 6:363–72 [Google Scholar]
  195. Reddy P, Ocampo A, Suzuki K, Luo J, Bacman SR. 195.  et al. 2015. Selective elimination of mitochondrial mutations in the germline by genome editing. Cell 161:459–69 [Google Scholar]
  196. Lanphier E, Urnov F, Haecker SE, Werner M, Smolenski J. 196.  2015. Don't edit the human germ line. Nature 519:410–11 [Google Scholar]
  197. Baltimore D, Berg P, Botchan M, Carroll D, Charo RA. 197.  et al. 2015. A prudent path forward for genomic engineering and germline gene modification. Science 348:36–38 [Google Scholar]
  198. Porteus MH, Dann CT. 198.  2015. Genome editing of the germline: broadening the discussion. Mol. Ther. 23:980–82 [Google Scholar]
  199. Miller HI. 199.  2015. Germline gene therapy: We're ready. Science 348:1325 [Google Scholar]
  200. Fanslow DA, Wirt SE, Barker JC, Connelly JP, Porteus MH, Dann CT. 200.  2014. Genome editing in mouse spermatogonial stem/progenitor cells using engineered nucleases. PLOS ONE 9:e112652 [Google Scholar]
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