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Cellular and Molecular Life Sciences

, Volume 72, Issue 20, pp 3819–3830 | Cite as

Recent developments and clinical studies utilizing engineered zinc finger nuclease technology

  • Young-Il Jo
  • Hyongbum Kim
  • Suresh RamakrishnaEmail author
Review

Abstract

Efficient methods for creating targeted genetic modifications have long been sought for the investigation of gene function and the development of therapeutic modalities for various diseases, including genetic disorders. Although such modifications are possible using homologous recombination, the efficiency is extremely low. Zinc finger nucleases (ZFNs) are custom-designed artificial nucleases that make double-strand breaks at specific sequences, enabling efficient targeted genetic modifications such as corrections, additions, gene knockouts and structural variations. ZFNs are composed of two domains: (i) a DNA-binding domain comprised of zinc finger modules and (ii) the FokI nuclease domain that cleaves the DNA strand. Over 17 years after ZFNs were initially developed, a number of improvements have been made. Here, we will review the developments and future perspectives of ZFN technology. For example, ZFN activity and specificity have been significantly enhanced by modifying the DNA-binding domain and FokI cleavage domain. Advances in culture methods, such as the application of a cold shock and the use of small molecules that affect ZFN stability, have also increased ZFN activity. Furthermore, ZFN-induced mutant cells can be enriched using episomal surrogate reporters. Additionally, we discuss several ongoing clinical studies that are based on ZFN-mediated genome editing in humans. These breakthroughs have substantially facilitated the use of ZFNs in research, medicine and biotechnology.

Keywords

Farm animals Pre-clinical trials Programmable nucleases Targeted genetic modifications Therapeutic applications ZFN architecture ZFN delivery ZFN modification 

Notes

Acknowledgments

We sincerely thank Dr. Eric Richardson (Hanyang University, Seoul, South Korea) for his critical comments on the manuscript. We would like to thank all the Suri’s Lab members for their helpful discussions. This study was supported by a grant of the Hanyang University (201500000000436), The Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI14C2019 (Medistar program)) and the National Research Foundation of Korea (2014R1A1A1A05006189, 2011-0019357, and 2013M3A9B4076544).

References

  1. 1.
    Carbery ID, Ji D, Harrington A, Brown V, Weinstein EJ, Liaw L, Cui X (2010) Targeted genome modification in mice using zinc-finger nucleases. Genetics 186(2):451–459. doi: 10.1534/genetics.110.117002 PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Cui X, Ji D, Fisher DA, Wu Y, Briner DM, Weinstein EJ (2011) Targeted integration in rat and mouse embryos with zinc-finger nucleases. Nat Biotechnol 29(1):64–67. doi: 10.1038/nbt.1731 PubMedCrossRefGoogle Scholar
  3. 3.
    Soldner F, Laganiere J, Cheng AW, Hockemeyer D, Gao Q, Alagappan R, Khurana V, Golbe LI, Myers RH, Lindquist S, Zhang L, Guschin D, Fong LK, Vu BJ, Meng X, Urnov FD, Rebar EJ, Gregory PD, Zhang HS, Jaenisch R (2011) Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell 146(2):318–331. doi: 10.1016/j.cell.2011.06.019 PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Shukla VK, Doyon Y, Miller JC, DeKelver RC, Moehle EA, Worden SE, Mitchell JC, Arnold NL, Gopalan S, Meng X, Choi VM, Rock JM, Wu YY, Katibah GE, Zhifang G, McCaskill D, Simpson MA, Blakeslee B, Greenwalt SA, Butler HJ, Hinkley SJ, Zhang L, Rebar EJ, Gregory PD, Urnov FD (2009) Precise genome modification in the crop species Zea mays using zinc-finger nucleases. Nature 459(7245):437–441. doi: 10.1038/nature07992 PubMedCrossRefGoogle Scholar
  5. 5.
    Townsend JA, Wright DA, Winfrey RJ, Fu F, Maeder ML, Joung JK, Voytas DF (2009) High-frequency modification of plant genes using engineered zinc-finger nucleases. Nature 459(7245):442–445. doi: 10.1038/nature07845 PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Li T, Liu B, Spalding MH, Weeks DP, Yang B (2012) High-efficiency TALEN-based gene editing produces disease-resistant rice. Nat Biotechnol 30(5):390–392. doi: 10.1038/nbt.2199 PubMedCrossRefGoogle Scholar
  7. 7.
    Rouet P, Smih F, Jasin M (1994) Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol Cell Biol 14(12):8096–8106PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Jasin M (1996) Genetic manipulation of genomes with rare-cutting endonucleases. Trends Genet TIG 12(6):224–228PubMedCrossRefGoogle Scholar
  9. 9.
    Bibikova M, Carroll D, Segal DJ, Trautman JK, Smith J, Kim YG, Chandrasegaran S (2001) Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. Mol Cell Biol 21(1):289–297. doi: 10.1128/MCB.21.1.289-297.2001 PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Bibikova M, Beumer K, Trautman JK, Carroll D (2003) Enhancing gene targeting with designed zinc finger nucleases. Science 300(5620):764. doi: 10.1126/science.1079512 PubMedCrossRefGoogle Scholar
  11. 11.
    Porteus MH, Baltimore D (2003) Chimeric nucleases stimulate gene targeting in human cells. Science 300(5620):763. doi: 10.1126/science.1078395 PubMedCrossRefGoogle Scholar
  12. 12.
    Bibikova M, Golic M, Golic KG, Carroll D (2002) Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-finger nucleases. Genetics 161(3):1169–1175PubMedCentralPubMedGoogle Scholar
  13. 13.
    Kim YG, Cha J, Chandrasegaran S (1996) Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci USA 93(3):1156–1160PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Porteus MH, Carroll D (2005) Gene targeting using zinc finger nucleases. Nat Biotechnol 23(8):967–973. doi: 10.1038/nbt1125 PubMedCrossRefGoogle Scholar
  15. 15.
    Lieber MR (2010) The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79:181–211. doi: 10.1146/annurev.biochem.052308.093131 PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Moynahan ME, Jasin M (2010) Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol 11(3):196–207. doi: 10.1038/nrm2851 PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S, Jamieson AC, Porteus MH, Gregory PD, Holmes MC (2005) Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435(7042):646–651. doi: 10.1038/nature03556 PubMedCrossRefGoogle Scholar
  18. 18.
    Morton J, Davis MW, Jorgensen EM, Carroll D (2006) Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells. Proc Natl Acad Sci USA 103(44):16370–16375. doi: 10.1073/pnas.0605633103 PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA (2008) Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol 26(6):695–701. doi: 10.1038/nbt1398 PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Doyon Y, McCammon JM, Miller JC, Faraji F, Ngo C, Katibah GE, Amora R, Hocking TD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Amacher SL (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26(6):702–708. doi: 10.1038/nbt1409 PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Geurts AM, Cost GJ, Freyvert Y, Zeitler B, Miller JC, Choi VM, Jenkins SS, Wood A, Cui X, Meng X, Vincent A, Lam S, Michalkiewicz M, Schilling R, Foeckler J, Kalloway S, Weiler H, Menoret S, Anegon I, Davis GD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jacob HJ, Buelow R (2009) Knockout rats via embryo microinjection of zinc-finger nucleases. Science 325(5939):433. doi: 10.1126/science.1172447 PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Lloyd A, Plaisier CL, Carroll D, Drews GN (2005) Targeted mutagenesis using zinc-finger nucleases in Arabidopsis. Proc Natl Acad Sci USA 102(6):2232–2237. doi: 10.1073/pnas.0409339102 PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Wright DA, Townsend JA, Winfrey RJ Jr, Irwin PA, Rajagopal J, Lonosky PM, Hall BD, Jondle MD, Voytas DF (2005) High-frequency homologous recombination in plants mediated by zinc-finger nucleases. Plant J Cell Mol Biol 44(4):693–705. doi: 10.1111/j.1365-313X.2005.02551.x CrossRefGoogle Scholar
  24. 24.
    Lombardo A, Genovese P, Beausejour CM, Colleoni S, Lee YL, Kim KA, Ando D, Urnov FD, Galli C, Gregory PD, Holmes MC, Naldini L (2007) Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat Biotechnol 25(11):1298–1306. doi: 10.1038/nbt1353 PubMedCrossRefGoogle Scholar
  25. 25.
    Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA, Liu O, Wang N, Lee G, Bartsevich VV, Lee YL, Guschin DY, Rupniewski I, Waite AJ, Carpenito C, Carroll RG, Orange JS, Urnov FD, Rebar EJ, Ando D, Gregory PD, Riley JL, Holmes MC, June CH (2008) Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol 26(7):808–816. doi: 10.1038/nbt1410 PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Palpant NJ, Dudzinski D (2013) Zinc finger nucleases: looking toward translation. Gene Ther 20(2):121–127. doi: 10.1038/gt.2012.2 PubMedCrossRefGoogle Scholar
  27. 27.
    Wijshake T, Baker DJ, van de Sluis B (2014) Endonucleases: new tools to edit the mouse genome. Biochim Biophys Acta 1842(10):1942–1950. doi: 10.1016/j.bbadis.2014.04.020 PubMedCrossRefGoogle Scholar
  28. 28.
    Petersen B, Niemann H (2015) Advances in genetic modification of farm animals using zinc-finger nucleases (ZFN). Chromosome Res Int J Mol Supramol Evolut Asp Chromosome Biol 23(1):7–15. doi: 10.1007/s10577-014-9451-7 CrossRefGoogle Scholar
  29. 29.
    Miller JC, Holmes MC, Wang J, Guschin DY, Lee YL, Rupniewski I, Beausejour CM, Waite AJ, Wang NS, Kim KA, Gregory PD, Pabo CO, Rebar EJ (2007) An improved zinc-finger nuclease architecture for highly specific genome editing. Nat Biotechnol 25(7):778–785. doi: 10.1038/nbt1319 PubMedCrossRefGoogle Scholar
  30. 30.
    Szczepek M, Brondani V, Buchel J, Serrano L, Segal DJ, Cathomen T (2007) Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases. Nat Biotechnol 25(7):786–793. doi: 10.1038/nbt1317 PubMedCrossRefGoogle Scholar
  31. 31.
    Guo J, Gaj T, Barbas CF 3rd (2010) Directed evolution of an enhanced and highly efficient FokI cleavage domain for zinc finger nucleases. J Mol Biol 400(1):96–107. doi: 10.1016/j.jmb.2010.04.060 PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Ramakrishna S, Kim YH, Kim H (2013) Stability of zinc finger nuclease protein is enhanced by the proteasome inhibitor MG132. PLoS One 8(1):e54282. doi: 10.1371/journal.pone.0054282 PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Li H, Haurigot V, Doyon Y, Li T, Wong SY, Bhagwat AS, Malani N, Anguela XM, Sharma R, Ivanciu L, Murphy SL, Finn JD, Khazi FR, Zhou S, Paschon DE, Rebar EJ, Bushman FD, Gregory PD, Holmes MC, High KA (2011) In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature 475(7355):217–221. doi: 10.1038/nature10177 PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Gaj T, Guo J, Kato Y, Sirk SJ, Barbas CF 3rd (2012) Targeted gene knockout by direct delivery of zinc-finger nuclease proteins. Nat Methods 9(8):805–807. doi: 10.1038/nmeth.2030 PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Handel EM, Gellhaus K, Khan K, Bednarski C, Cornu TI, Muller-Lerch F, Kotin RM, Heilbronn R, Cathomen T (2012) Versatile and efficient genome editing in human cells by combining zinc-finger nucleases with adeno-associated viral vectors. Hum Gene Ther 23(3):321–329. doi: 10.1089/hum.2011.140 PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Kim H, Um E, Cho SR, Jung C, Kim JS (2011) Surrogate reporters for enrichment of cells with nuclease-induced mutations. Nat Methods 8(11):941–943. doi: 10.1038/nmeth.1733 PubMedCrossRefGoogle Scholar
  37. 37.
    Kim H, Kim MS, Wee G, Lee CI, Kim JS (2013) Magnetic separation and antibiotics selection enable enrichment of cells with ZFN/TALEN-induced mutations. PLoS One 8(2):e56476. doi: 10.1371/journal.pone.0056476 PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Wolfe SA, Nekludova L, Pabo CO (2000) DNA recognition by Cys2His2 zinc finger proteins. Annu Rev Biophys Biomol Struct 29:183–212. doi: 10.1146/annurev.biophys.29.1.183 PubMedCrossRefGoogle Scholar
  39. 39.
    Mani M, Smith J, Kandavelou K, Berg JM, Chandrasegaran S (2005) Binding of two zinc finger nuclease monomers to two specific sites is required for effective double-strand DNA cleavage. Biochem Biophys Res Commun 334(4):1191–1197. doi: 10.1016/j.bbrc.2005.07.021 PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Smith J, Bibikova M, Whitby FG, Reddy AR, Chandrasegaran S, Carroll D (2000) Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains. Nucleic Acids Res 28(17):3361–3369PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Mani M, Kandavelou K, Dy FJ, Durai S, Chandrasegaran S (2005) Design, engineering, and characterization of zinc finger nucleases. Biochem Biophys Res Commun 335(2):447–457. doi: 10.1016/j.bbrc.2005.07.089 PubMedCrossRefGoogle Scholar
  42. 42.
    Dreier B, Beerli RR, Segal DJ, Flippin JD, Barbas CF 3rd (2001) Development of zinc finger domains for recognition of the 5′-ANN-3′ family of DNA sequences and their use in the construction of artificial transcription factors. J Biol Chem 276(31):29466–29478. doi: 10.1074/jbc.M102604200 PubMedCrossRefGoogle Scholar
  43. 43.
    Pabo CO, Peisach E, Grant RA (2001) Design and selection of novel Cys2His2 zinc finger proteins. Annu Rev Biochem 70:313–340. doi: 10.1146/annurev.biochem.70.1.313 PubMedCrossRefGoogle Scholar
  44. 44.
    Bae KH, Kwon YD, Shin HC, Hwang MS, Ryu EH, Park KS, Yang HY, Lee DK, Lee Y, Park J, Kwon HS, Kim HW, Yeh BI, Lee HW, Sohn SH, Yoon J, Seol W, Kim JS (2003) Human zinc fingers as building blocks in the construction of artificial transcription factors. Nat Biotechnol 21(3):275–280. doi: 10.1038/nbt796 PubMedCrossRefGoogle Scholar
  45. 45.
    Blancafort P, Magnenat L, Barbas CF (2003) Scanning the human genome with combinatorial transcription factor libraries. Nat Biotechnol 21:269–274PubMedCrossRefGoogle Scholar
  46. 46.
    Lee DK, Seol W, Kim JS (2003) Custom DNA-binding proteins and artificial transcription factors. Curr Top Med Chem 3(6):645–657PubMedCrossRefGoogle Scholar
  47. 47.
    Jamieson AC, Miller JC, Pabo CO (2003) Drug discovery with engineered zinc-finger proteins. Nat Rev Drug Discov 2(5):361–368. doi: 10.1038/nrd1087 PubMedCrossRefGoogle Scholar
  48. 48.
    Park KS, Lee DK, Lee H, Lee Y, Jang YS, Kim YH, Yang HY, Lee SI, Seol W, Kim JS (2003) Phenotypic alteration of eukaryotic cells using randomized libraries of artificial transcription factors. Nat Biotechnol 21(10):1208–1214. doi: 10.1038/nbt868 PubMedCrossRefGoogle Scholar
  49. 49.
    Carroll D, Morton JJ, Beumer KJ, Segal DJ (2006) Design, construction and in vitro testing of zinc finger nucleases. Nat Protoc 1(3):1329–1341. doi: 10.1038/nprot.2006.231 PubMedCrossRefGoogle Scholar
  50. 50.
    Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM, Eichtinger M, Jiang T, Foley JE, Winfrey RJ, Townsend JA, Unger-Wallace E, Sander JD, Muller-Lerch F, Fu F, Pearlberg J, Gobel C, Dassie JP, Pruett-Miller SM, Porteus MH, Sgroi DC, Iafrate AJ, Dobbs D, McCray PB Jr, Cathomen T, Voytas DF, Joung JK (2008) Rapid “open-source” engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol Cell 31(2):294–301. doi: 10.1016/j.molcel.2008.06.016 PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Mandell JG, Barbas CF, 3rd (2006) Zinc Finger Tools: custom DNA-binding domains for transcription factors and nucleases. Nucleic Acids Res 34(Web Server issue):W516–W523. doi: 10.1093/nar/gkl209
  52. 52.
    Sander JD, Zaback P, Joung JK, Voytas DF, Dobbs D (2007) Zinc Finger Targeter (ZiFiT): an engineered zinc finger/target site design tool. Nucleic Acids Res 35(Web Server issue):W599–W605. doi: 10.1093/nar/gkm349
  53. 53.
    Kim HJ, Lee HJ, Kim H, Cho SW, Kim JS (2009) Targeted genome editing in human cells with zinc finger nucleases constructed via modular assembly. Genome Res 19(7):1279–1288. doi: 10.1101/gr.089417.108 PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD (2010) Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11(9):636–646. doi: 10.1038/nrg2842 PubMedCrossRefGoogle Scholar
  55. 55.
    Carroll D (2011) Genome engineering with zinc-finger nucleases. Genetics 188(4):773–782. doi: 10.1534/genetics.111.131433 PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Joung JK, Ramm EI, Pabo CO (2000) A bacterial two-hybrid selection system for studying protein-DNA and protein-protein interactions. Proc Natl Acad Sci USA 97(13):7382–7387. doi: 10.1073/pnas.110149297 PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Hurt JA, Thibodeau SA, Hirsh AS, Pabo CO, Joung JK (2003) Highly specific zinc finger proteins obtained by directed domain shuffling and cell-based selection. Proc Natl Acad Sci USA 100(21):12271–12276. doi: 10.1073/pnas.2135381100 PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Durai S, Bosley A, Abulencia AB, Chandrasegaran S, Ostermeier M (2006) A bacterial one-hybrid selection system for interrogating zinc finger-DNA interactions. Comb Chem High Throughput Screen 9(4):301–311PubMedCrossRefGoogle Scholar
  59. 59.
    Meng X, Brodsky MH, Wolfe SA (2005) A bacterial one-hybrid system for determining the DNA-binding specificity of transcription factors. Nat Biotechnol 23(8):988–994. doi: 10.1038/nbt1120 PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Maeder ML, Thibodeau-Beganny S, Sander JD, Voytas DF, Joung JK (2009) Oligomerized pool engineering (OPEN): an ‘open-source’ protocol for making customized zinc-finger arrays. Nat Protoc 4(10):1471–1501. doi: 10.1038/nprot.2009.98 PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Foley JE, Yeh JR, Maeder ML, Reyon D, Sander JD, Peterson RT, Joung JK (2009) Rapid mutation of endogenous zebrafish genes using zinc finger nucleases made by Oligomerized Pool ENgineering (OPEN). PLoS One 4(2):e4348. doi: 10.1371/journal.pone.0004348 PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Zou J, Maeder ML, Mali P, Pruett-Miller SM, Thibodeau-Beganny S, Chou BK, Chen G, Ye Z, Park IH, Daley GQ, Porteus MH, Joung JK, Cheng L (2009) Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell 5(1):97–110. doi: 10.1016/j.stem.2009.05.023 PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Sander JD, Dahlborg EJ, Goodwin MJ, Cade L, Zhang F, Cifuentes D, Curtin SJ, Blackburn JS, Thibodeau-Beganny S, Qi Y, Pierick CJ, Hoffman E, Maeder ML, Khayter C, Reyon D, Dobbs D, Langenau DM, Stupar RM, Giraldez AJ, Voytas DF, Peterson RT, Yeh JR, Joung JK (2011) Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Methods 8(1):67–69. doi: 10.1038/nmeth.1542 PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Cornu TI, Thibodeau-Beganny S, Guhl E, Alwin S, Eichtinger M, Joung JK, Cathomen T (2008) DNA-binding specificity is a major determinant of the activity and toxicity of zinc-finger nucleases. Mol Ther J Am Soc Gene Ther 16(2):352–358. doi: 10.1038/sj.mt.6300357 CrossRefGoogle Scholar
  65. 65.
    Bahassi EM, Salmon MA, Van Melderen L, Bernard P, Couturier M (1995) F plasmid CcdB killer protein: ccdB gene mutants coding for non-cytotoxic proteins which retain their regulatory functions. Mol Microbiol 15(6):1031–1037PubMedCrossRefGoogle Scholar
  66. 66.
    Ramirez CL, Certo MT, Mussolino C, Goodwin MJ, Cradick TJ, McCaffrey AP, Cathomen T, Scharenberg AM, Joung JK (2012) Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects. Nucleic Acids Res 40(12):5560–5568. doi: 10.1093/nar/gks179 PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Doyon Y, Choi VM, Xia DF, Vo TD, Gregory PD, Holmes MC (2010) Transient cold shock enhances zinc-finger nuclease-mediated gene disruption. Nat Methods 7(6):459–460. doi: 10.1038/nmeth.1456 PubMedCrossRefGoogle Scholar
  68. 68.
    Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, DeKelver RC, Katibah GE, Amora R, Boydston EA, Zeitler B, Meng X, Miller JC, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jaenisch R (2009) Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol 27(9):851–857. doi: 10.1038/nbt.1562 PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Lombardo A, Cesana D, Genovese P, Di Stefano B, Provasi E, Colombo DF, Neri M, Magnani Z, Cantore A, Lo Riso P, Damo M, Pello OM, Holmes MC, Gregory PD, Gritti A, Broccoli V, Bonini C, Naldini L (2011) Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat Methods 8(10):861–869. doi: 10.1038/nmeth.1674 PubMedCrossRefGoogle Scholar
  70. 70.
    Zou J, Mali P, Huang X, Dowey SN, Cheng L (2011) Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease. Blood 118(17):4599–4608. doi: 10.1182/blood-2011-02-335554 PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Zou J, Sweeney CL, Chou BK, Choi U, Pan J, Wang H, Dowey SN, Cheng L, Malech HL (2011) Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease-mediated safe harbor targeting. Blood 117(21):5561–5572. doi: 10.1182/blood-2010-12-328161 PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Chen Z, Jaafar L, Agyekum DG, Xiao H, Wade MF, Kumaran RI, Spector DL, Bao G, Porteus MH, Dynan WS, Meiler SE (2013) Receptor-mediated delivery of engineered nucleases for genome modification. Nucleic Acids Res 41(19):e182. doi: 10.1093/nar/gkt710 PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Flisikowska T, Kind A, Schnieke A (2014) Genetically modified pigs to model human diseases. Journal of applied genetics 55(1):53–64. doi: 10.1007/s13353-013-0182-9 PubMedCrossRefGoogle Scholar
  74. 74.
    Petersen B, Niemann H (2015) Molecular scissors and their application in genetically modified farm animals. Transgenic Res 24(3):381–396. doi: 10.1007/s11248-015-9862-z PubMedCrossRefGoogle Scholar
  75. 75.
    Hauschild-Quintern J, Petersen B, Cost GJ, Niemann H (2013) Gene knockout and knockin by zinc-finger nucleases: current status and perspectives. Cellular and molecular life sciences : CMLS 70(16):2969–2983. doi: 10.1007/s00018-012-1204-1 PubMedCrossRefGoogle Scholar
  76. 76.
    Watanabe M, Umeyama K, Matsunari H, Takayanagi S, Haruyama E, Nakano K, Fujiwara T, Ikezawa Y, Nakauchi H, Nagashima H (2010) Knockout of exogenous EGFP gene in porcine somatic cells using zinc-finger nucleases. Biochem Biophys Res Commun 402(1):14–18. doi: 10.1016/j.bbrc.2010.09.092 PubMedCrossRefGoogle Scholar
  77. 77.
    Whyte JJ, Zhao J, Wells KD, Samuel MS, Whitworth KM, Walters EM, Laughlin MH, Prather RS (2011) Gene targeting with zinc finger nucleases to produce cloned eGFP knockout pigs. Mol Reprod Dev 78(1):2. doi: 10.1002/mrd.21271 PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Yang D, Yang H, Li W, Zhao B, Ouyang Z, Liu Z, Zhao Y, Fan N, Song J, Tian J, Li F, Zhang J, Chang L, Pei D, Chen YE, Lai L (2011) Generation of PPARgamma mono-allelic knockout pigs via zinc-finger nucleases and nuclear transfer cloning. Cell Res 21(6):979–982. doi: 10.1038/cr.2011.70 PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Hauschild J, Petersen B, Santiago Y, Queisser AL, Carnwath JW, Lucas-Hahn A, Zhang L, Meng X, Gregory PD, Schwinzer R, Cost GJ, Niemann H (2011) Efficient generation of a biallelic knockout in pigs using zinc-finger nucleases. Proc Natl Acad Sci USA 108(29):12013–12017. doi: 10.1073/pnas.1106422108 PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Li P, Estrada JL, Burlak C, Tector AJ (2013) Biallelic knockout of the alpha-1,3 galactosyltransferase gene in porcine liver-derived cells using zinc finger nucleases. J Surg Res 181(1):e39–e45. doi: 10.1016/j.jss.2012.06.035 PubMedCrossRefGoogle Scholar
  81. 81.
    Bao L, Chen H, Jong U, Rim C, Li W, Lin X, Zhang D, Luo Q, Cui C, Huang H, Zhang Y, Xiao L, Fu Z (2014) Generation of GGTA1 biallelic knockout pigs via zinc-finger nucleases and somatic cell nuclear transfer. Sci China Life Sci 57(2):263–268. doi: 10.1007/s11427-013-4601-2 PubMedCrossRefGoogle Scholar
  82. 82.
    Yu S, Luo J, Song Z, Ding F, Dai Y, Li N (2011) Highly efficient modification of beta-lactoglobulin (BLG) gene via zinc-finger nucleases in cattle. Cell Res 21(11):1638–1640. doi: 10.1038/cr.2011.153 PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Liu X, Wang Y, Tian Y, Yu Y, Gao M, Hu G, Su F, Pan S, Luo Y, Guo Z, Quan F, Zhang Y (2014) Generation of mastitis resistance in cows by targeting human lysozyme gene to beta-casein locus using zinc-finger nucleases. Proc Biol Sci/R Soc 281(1780):20133368. doi: 10.1098/rspb.2013.3368 CrossRefGoogle Scholar
  84. 84.
    Liu X, Wang Y, Guo W, Chang B, Liu J, Guo Z, Quan F, Zhang Y (2013) Zinc-finger nickase-mediated insertion of the lysostaphin gene into the beta-casein locus in cloned cows. Nat Commun 4:2565. doi: 10.1038/ncomms3565 PubMedCentralPubMedGoogle Scholar
  85. 85.
    Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC, Zeitler B, Cherone JM, Meng X, Hinkley SJ, Rebar EJ, Gregory PD, Urnov FD, Jaenisch R (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29(8):731–734. doi: 10.1038/nbt.1927 PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    Cho SW, Kim S, Kim JM, Kim JS (2013) Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol 31(3):230–232. doi: 10.1038/nbt.2507 PubMedCrossRefGoogle Scholar
  87. 87.
    Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339(6121):819–823. doi: 10.1126/science.1231143 PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Hwang WY, Fu Y, Reyon D, Maeder ML, Tsai SQ, Sander JD, Peterson RT, Yeh JR, Joung JK (2013) Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol 31(3):227–229. doi: 10.1038/nbt.2501 PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Jiang W, Bikard D, Cox D, Zhang F, Marraffini LA (2013) RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nat Biotechnol 31(3):233–239. doi: 10.1038/nbt.2508 PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM (2013) RNA-guided human genome engineering via Cas9. Science 339(6121):823–826. doi: 10.1126/science.1232033 PubMedCentralPubMedCrossRefGoogle Scholar
  91. 91.
    Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA (1996) CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272(5270):1955–1958PubMedCrossRefGoogle Scholar
  92. 92.
    Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381(6584):661–666. doi: 10.1038/381661a0 PubMedCrossRefGoogle Scholar
  93. 93.
    Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H, Koup RA, Landau NR (1996) Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86(3):367–377PubMedCrossRefGoogle Scholar
  94. 94.
    Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M (1996) Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382(6593):722–725. doi: 10.1038/382722a0 PubMedCrossRefGoogle Scholar
  95. 95.
    Maier DA, Brennan AL, Jiang S, Binder-Scholl GK, Lee G, Plesa G, Zheng Z, Cotte J, Carpenito C, Wood T, Spratt SK, Ando D, Gregory P, Holmes MC, Perez EE, Riley JL, Carroll RG, June CH, Levine BL (2013) Efficient clinical scale gene modification via zinc finger nuclease-targeted disruption of the HIV co-receptor CCR5. Hum Gene Ther 24(3):245–258. doi: 10.1089/hum.2012.172 PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Voit RA, McMahon MA, Sawyer SL, Porteus MH (2013) Generation of an HIV resistant T-cell line by targeted “stacking” of restriction factors. Mol Ther J Am Soc Gene Ther 21(4):786–795. doi: 10.1038/mt.2012.284 CrossRefGoogle Scholar
  97. 97.
    Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K, Schneider T, Hofmann J, Kucherer C, Blau O, Blau IW, Hofmann WK, Thiel E (2009) Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 360(7):692–698. doi: 10.1056/NEJMoa0802905 PubMedCrossRefGoogle Scholar
  98. 98.
    Li L, Krymskaya L, Wang J, Henley J, Rao A, Cao LF, Tran CA, Torres-Coronado M, Gardner A, Gonzalez N, Kim K, Liu PQ, Hofer U, Lopez E, Gregory PD, Liu Q, Holmes MC, Cannon PM, Zaia JA, Digiusto DL (2013) Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases. Mol Ther J Am Soc Gene Ther. doi: 10.1038/mt.2013.65 Google Scholar
  99. 99.
    Hofer U, Henley JE, Exline CM, Mulhern O, Lopez E, Cannon PM (2013) Pre-clinical modeling of CCR5 knockout in human hematopoietic stem cells by zinc finger nucleases using humanized mice. J Infect Dis 208(Suppl 2):S160–S164. doi: 10.1093/infdis/jit382 PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Li L, Krymskaya L, Wang J, Henley J, Rao A, Cao LF, Tran CA, Torres-Coronado M, Gardner A, Gonzalez N, Kim K, Liu PQ, Hofer U, Lopez E, Gregory PD, Liu Q, Holmes MC, Cannon PM, Zaia JA, DiGiusto DL (2013) Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases. Mol Ther J Am Soc Gene Ther 21(6):1259–1269. doi: 10.1038/mt.2013.65 CrossRefGoogle Scholar
  101. 101.
    Haruta M, Tomita Y, Yuno A, Matsumura K, Ikeda T, Takamatsu K, Haga E, Koba C, Nishimura Y, Senju S (2013) TAP-deficient human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells. Gene Ther 20(5):504–513. doi: 10.1038/gt.2012.59 PubMedCrossRefGoogle Scholar
  102. 102.
    Wang Y, Zhang WY, Hu S, Lan F, Lee AS, Huber B, Lisowski L, Liang P, Huang M, de Almeida PE, Won JH, Sun N, Robbins RC, Kay MA, Urnov FD, Wu JC (2012) Genome editing of human embryonic stem cells and induced pluripotent stem cells with zinc finger nucleases for cellular imaging. Circ Res 111(12):1494–1503. doi: 10.1161/CIRCRESAHA.112.274969 PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Park A, Liegel RP, Ronchetti A, Ebert AD, Geurts A, Sidjanin DJ (2014) Targeted disruption of Tbc1d20 with zinc-finger nucleases causes cataracts and testicular abnormalities in mice. BMC Genet 15(1):135. doi: 10.1186/s12863-014-0135-2 PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Merling RK, Sweeney CL, Chu J, Bodansky A, Choi U, Priel DL, Kuhns DB, Wang H, Vasilevsky S, De Ravin SS, Winkler T, Dunbar CE, Zou J, Zarember KA, Gallin JI, Holland SM, Malech HL (2015) An AAVS1-targeted minigene platform for correction of iPSCs from all five types of chronic granulomatous disease. Mol Ther J Am Soc Gene Ther 23(1):147–157. doi: 10.1038/mt.2014.195 CrossRefGoogle Scholar
  105. 105.
    Hamilton SM, Green JR, Veeraragavan S, Yuva L, McCoy A, Wu Y, Warren J, Little L, Ji D, Cui X, Weinstein E, Paylor R (2014) Fmr1 and Nlgn3 knockout rats: novel tools for investigating autism spectrum disorders. Behav Neurosci 128(2):103–109. doi: 10.1037/a0035988 PubMedCrossRefGoogle Scholar
  106. 106.
    Sebastiano V, Maeder ML, Angstman JF, Haddad B, Khayter C, Yeo DT, Goodwin MJ, Hawkins JS, Ramirez CL, Batista LF, Artandi SE, Wernig M, Joung JK (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(11):1717–1726. doi: 10.1002/stem.718 PubMedCentralPubMedCrossRefGoogle Scholar
  107. 107.
    Yusa K, Rashid ST, Strick-Marchand H, Varela I, Liu PQ, Paschon DE, Miranda E, Ordonez A, Hannan NR, Rouhani FJ, Darche S, Alexander G, Marciniak SJ, Fusaki N, Hasegawa M, Holmes MC, Di Santo JP, Lomas DA, Bradley A, Vallier L (2011) Targeted gene correction of alpha1-antitrypsin deficiency in induced pluripotent stem cells. Nature 478(7369):391–394. doi: 10.1038/nature10424 PubMedCentralPubMedCrossRefGoogle Scholar
  108. 108.
    Kim H, Kim JS (2014) A guide to genome engineering with programmable nucleases. Nat Rev Genet 15(5):321–334. doi: 10.1038/nrg3686 PubMedCrossRefGoogle Scholar
  109. 109.
    Liang P, Xu Y, Zhang X, Ding C, Huang R, Zhang Z, Lv J, Xie X, Chen Y, Li Y, Sun Y, Bai Y, Songyang Z, Ma W, Zhou C, Huang J (2015) CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 6(5):363–372. doi: 10.1007/s13238-015-0153-5 PubMedCentralPubMedCrossRefGoogle Scholar
  110. 110.
    Kim YG, Chandrasegaran S (1994) Chimeric restriction endonuclease. Proc Natl Acad Sci USA 91(3):883–887PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Young-Il Jo
    • 1
  • Hyongbum Kim
    • 2
    • 3
  • Suresh Ramakrishna
    • 4
    Email author
  1. 1.Brandeis UniversityWalthamUSA
  2. 2.Department of Pharmacology and Brain Korea 21 PLUS Project for Medical ScienceYonsei University College of MedicineSeoulSouth Korea
  3. 3.Graduate Program of Nano Science and TechnologyYonsei UniversitySeoulSouth Korea
  4. 4.Graduate School of Biomedical Science and EngineeringHanyang UniversitySeoulSouth Korea

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