遗传 ›› 2011, Vol. 33 ›› Issue (7): 665-683.doi: 10.3724/SP.J.1005.2011.00665
• 综述 • 下一篇
肖安, 胡莹莹, 王唯晔, 杨志芃, 王展翔, 黄鹏, 佟向军, 张博, 林硕
收稿日期:2010-12-29
修回日期:2011-04-17
出版日期:2011-07-20
发布日期:2011-07-25
通讯作者:
张博
E-mail:bzhang@pku.edu.cn
基金资助:国家自然科学基金项目(编号：30730056, 30871418)和国家重点基础研究发展规划(973计划)项目(编号：2007CB914502, 2011CBA01002)资助
XIAO An, HU Ying-Ying, WANG Wei-Ye, YANG Zhi-Peng, WANG Zhan-Xiang, HUANG Peng, TONG Xiang-Jun, ZHANG Bo, LIN Shuo
Received:2010-12-29
Revised:2011-04-17
Online:2011-07-20
Published:2011-07-25
摘要： 锌指核酸酶(ZFN)由锌指蛋白(ZFP)结构域和Fok I核酸内切酶的切割结构域人工融合而成, 是近年来发展起来的一种可用于基因组定点改造的分子工具。ZFN可识别并结合特定的DNA序列, 并通过切割这一序列的特定位点造成DNA的双链断裂(DSB)。在此基础上, 人们可以对基因组的特定位点进行各种遗传操作, 包括基因打靶、基因定点插入、基因修复等, 从而能够方便快捷地对基因组实现靶向遗传修饰。这种新的基因组定点修饰方法的突出优势是适用性好, 对物种没有选择性, 并且可以在细胞和个体水平进行遗传操作。文章综述了ZFN技术的研究进展及应用前景, 重点介绍ZFN的结构与作用机制、现有的靶点评估及锌指蛋白库的构建与筛选方法、基因组定点修饰的策略, 以及目前利用这一技术已成功实现突变的物种及内源基因, 为开展这一领域的研究工作提供参考。
肖安，胡莹莹，王唯晔，杨志芃，王展翔，黄鹏，佟向军，张博，林硕. 人工锌指核酸酶介导的基因组定点修饰技术[J]. 遗传, 2011, 33(7): 665-683.
XIAO An, HU Ying-Ying, WANG Wei-Ye, YANG Zhi-Peng, WANG Zhan-Xiang, HUANG Feng, TONG Xiang-Jun, ZHANG Bo, LIN Shuo. Progress in zinc finger nuclease engineering for targeted genome modification[J]. HEREDITAS, 2011, 33(7): 665-683.
| [1] 孙振红, 苗向阳, 朱瑞良. 动物转基因新技术研究进展. 遗传, 2010, 32(6): 539-547.[2] Kim YG, Cha J, Chandrasegaran S. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci USA, 1996, 93(3): 1156-1160.[3] Klug A. The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation. Q Rev Biophys, 2010, 43(1): 1-21.[4] Miller J, McLachlan AD, Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J, 1985, 4(6): 1609-1614.[5] Wolfe SA, Nekludova L, Pabo CO. DNA recognition by Cys2His2 zinc finger proteins. Annu Rev Biophys Biomol Struct, 2000, 29(6): 183-212.[6] 钟强, 赵书红. 锌指蛋白核酸酶的作用原理及其应用. 遗传, 2010, 33(2): 123-130.[7] Porteus MH, Carroll D. Gene targeting using zinc finger nucleases. Nat Biotechnol, 2005, 23(8): 967-973.[8] Pavletich NP, Pabo CO. Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 Å. Science, 1991, 252(5007): 809-817.[9] Fu FL, Sander JD, Maeder M, Thibodeau-Beganny S, Joung JK, Dobbs D, Miller L, Voytas DF. Zinc Finger Database (ZiFDB): a repository for information on C2H2 zinc fingers and engineered zinc finger arrays. Nucleic Acids Res, 2009, 37(Suppl 1): D279-D283.[10] Jayakanthan M, Muthukumaran J, Chandrasekar S, Chawla K, Punetha A, Sundar D. ZifBASE: a database of zinc finger proteins and associated resources. BMC Genomics, 2009, 10(1): 421.[11] Wright DA, Thibodeau-Beganny S, Sander JD, Winfrey RJ, Hirsh AS, Eichtinger M, Fu FL, Porteus MH, Dobbs D, Voytas DF, Joung JK. Standardized reagents and protocols for engineering zinc finger nucleases by modular assembly. Nat Protoc, 2006, 1(3): 1637-1652.[12] Dreier B, Beerli RR, Segal DJ, Flippin JD, Barbas CF III. 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, 2001, 276(31): 29466-29478.[13] Dreier B, Fuller RP, Segal DJ, Lund CV, Blancafort P, Huber A, Koksch B, Barbas CF III. Development of zinc finger domains for recognition of the 5′-CNN-3′ family DNA sequences and their use in the construction of artificial transcription factors. J Biol Chem, 2005, 280(42): 35588-35597.[14] Segal DJ, Dreier B, Beerli RR, Barbas CF III. Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5′-GNN-3′ DNA target sequences. Proc Natl Acad Sci USA, 1999, 96(6): 2758-2763.[15] Liu Q, Xia ZQ, Case CC. Validated zinc finger protein designs for all 16 GNN DNA triplet targets. J Biol Chem, 2002, 277(6): 3850-3856.[16] Bae KH, Do Kwon Y, 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. Human zinc fingers as building blocks in the construction of artificial transcription factors. Nat Biotechnol, 2003, 21(3): 275-280.[17] Ramirez CL, Foley JE, Wright DA, Müller-Lerch F, Rahman SH, Cornu TI, Winfrey RJ, Sander JD, Fu FL, Townsend JA, Cathomen T, Voytas DF, Joung JK. Unexpected failure rates for modular assembly of engineered zinc fingers. Nat Methods, 2008, 5(5): 374-375.[18] Kim HJ, Lee HJ, Kim H, Cho SW, Kim JS. Targeted genome editing in human cells with zinc finger nucleases constructed via modular assembly. Genome Res, 2009, 19(7): 1279-1288.[19] 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, Müller-Lerch F, Fu FL, Pearlberg J, Göbel C, Dassie JP, Pruett-Miller SM, Porteus MH, Sgroi DC, Iafrate AJ, Dobbs D, McCray PB, Cathomen T, Voytas DF, Joung JK. Rapid “Open-Source” engineering of customized zinc finger nucleases for highly efficient gene modification. Mol Cell, 2008, 31(2): 294-301.[20] Meng XD, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA. Targeted gene inactivation in zebrafish using engineered zinc finger nucleases. Nat Biotechnol, 2008, 26(6): 695-701.[21] Sander JD, Dahlborg EJ, Goodwin MJ, Cade L, Zhang F, Cifuentes D, Curtin SJ, Blackburn JS, Thibodeau-Beganny S, Qi YP, Pierick CJ, Hoffman E, Maeder ML, Khayter C, Reyon D, Dobbs D, Langenau DM, Stupar RM, Giraldez AJ, Voytas DF, Peterson RT, Yeh JRJ, Joung JK. Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Methods, 2011, 8(1): 67-69.[22] Sander JD, Maeder ML, Reyon D, Voytas DF, Joung JK, Dobbs D. ZiFiT (Zinc Finger Targeter): an updated zinc finger engineering tool. Nucleic Acids Res, 2010, 38(Suppl. 2): W462-W468.[23] Sander JD, Reyon D, Maeder ML, Foley JE, Thibodeau-Beganny S, Li XH, Regan MR, Dahlborg EJ, Goodwin MJ, Fu FL, Voytas DF, Joung JK, Dobbs D. Predicting success of oligomerized pool engineering (OPEN) for zinc finger target site sequences. BMC Bioinformatics, 2010, 11: 53.[24] Mandell JG, Barbas CF III. Zinc Finger Tools: custom DNA-binding domains for transcription factors and nucleases. Nucleic Acids Res, 2006, 34(Suppl. 2): W516-W523.[25] Reyon D, Kirkpatrick JR, Sander JD, Zhang F, Voytas DF, Joung JK, Dobbs D, Coffman CR. ZFNGenome: A comprehensive resource for locating zinc finger nuclease target sites in model organisms. BMC Genomics, 2011, 12(1): 83.[26] Looney MC, Moran LS, Jack WE, Feehery GR, Benner JS, Slatko BE, Wilson GG. Nucleotide sequence of the FokI restriction-modification system: separate strand-specificity domains in the methyltransferase. Gene, 1989, 80(2): 193-208.[27] Bitinaite J, Wah DA, Aggarwal AK, Schildkraut I. FokI dimerization is required for DNA cleavage. Proc Natl Acad Sci USA, 1998, 95(18): 10570-10575.[28] Vanamee ÉS, Santagata S, Aggarwal AK. FokI requires two specific DNA sites for cleavage. J Mol Biol, 2001, 309(1): 69-78.[29] Smith J, Bibikova M, Whitby FG, Reddy AR, Chandrasegaran S, Carroll D. Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains. Nucleic Acids Res, 2000, 28(17): 3361-3369.[30] Bibikova M, Carroll D, Segal DJ, Trautman JK, Smith J, Kim YG, Chandrasegaran S. Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. Mol Cell Biol, 2001, 21(1): 289-297.[31] Handel EM, Alwin S, Cathomen T. Expanding or restricting the target site repertoire of zinc-finger nucleases: the inter-domain linker as a major determinant of target site selectivity. Mol Ther, 2008, 17(1): 104-111.[32] Szczepek M, Brondani V, Büchel J, Serrano L, Segal DJ, Cathomen T. Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases. Nat Biotechnol, 2007, 25(7): 786-793.[33] Doyon Y, Vo TD, Mendel MC, Greenberg SG, Wang JB, Xia DF, Miller JC, Urnov FD, Gregory PD, Holmes MC. Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nat Methods, 2011, 8(1): 74-79.[34] Miller JC, Holmes MC, Wang JB, Guschin DY, Lee YL, Rupniewski I, Beausejour CM, Waite AJ, Wang NS, Kim KA, Gregory PD, Pabo CO, Rebar EJ. An improved zinc-finger nuclease architecture for highly specific genome editing. Nat Biotechnol, 2007, 25(7): 778-785.[35] Ramalingam S, Kandavelou K, Rajenderan R, Chandrasegaran S. Creating designed zinc-finger nucleases with minimal cytotoxicity. J Mol Biol, 2011, 405(3): 630-641.[36] Guo J, Gaj T, Barbas CF III. Directed evolution of an enhanced and highly efficient foki cleavage domain for zinc finger nucleases. J Mol Biol, 2010, 400(1): 96-107.[37] Bibikova M, Golic M, Golic KG, Carroll D. Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-finger nucleases. Genetics, 2002, 161(3): 1169-1175.[38] Orlando SJ, Santiago Y, DeKelver RC, Freyvert Y, Boydston EA, Moehle EA, Choi VM, Gopalan SM, Lou JF, Li J, Miller JC, Holmes MC, Gregory PD, Urnov FD, Cost GJ. Zinc-finger nuclease-driven targeted integration into mammalian genomes using donors with limited chromosomal homology. Nucleic Acids Res, 2010, 38(15): e152.[39] Bibikova M, Beumer K, Trautman JK, Carroll D. Enhancing gene targeting with designed zinc finger nucleases. Science, 2003, 300(5620): 764.[40] Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S, Jamieson AC, Porteus MH, Gregory PD, Holmes MC. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature, 2005, 435(7042): 646-651.[41] Lee HJ, Kim E, Kim JS. Targeted chromosomal deletions in human cells using zinc finger nucleases. Genome Res, 2010, 20(1): 81-89.[42] 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. Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol, 2008, 26(6): 702-708.[43] Foley JE, Yeh JRJ, Maeder ML, Reyon D, Sander JD, Peterson RT, Joung JK. Rapid mutation of endogenous zebrafish genes using zinc finger nucleases made by Oligomerized Pool ENgineering (OPEN). PLoS ONE, 2009, 4(2): e4348.[44] Geurts AM, Cost GJ, Freyvert Y, Zeitler B, Miller JC, Choi VM, Jenkins SS, Wood A, Cui XX, Meng XD, Vincent A, Lam S, Michalkiewicz M, Schilling R, Foeckler J, Kalloway S, Weiler H, Ménoret S, Anegon I, Davis GD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jacob HJ, Buelow R. Knockout rats via embryo microinjection of zinc-finger nucleases. Science, 2009, 325(5939): 433-433.[45] Cui XX, Ji DN, Fisher DA, Wu YM, Briner DM, Weinstein EJ. Targeted integration in rat and mouse embryos with zinc-finger nucleases. Nat Biotechnol, 2011, 29(1): 64-67.[46] Moehle EA, Rock JM, Lee YL, Jouvenot Y, DeKelver RC, Gregory PD, Urnov FD, Holmes MC. Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases. Proc Natl Acad Sci USA, 2007, 104(9): 3055-3060.[47] Perez EE, Wang JB, 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. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol, 2008, 26(7): 808-816.[48] DeKelver RC, Choi VM, Moehle EA, Paschon DE, Hockemeyer D, Meijsing SH, Sancak Y, Cui XX, Steine ELJ, Miller JC, Tam P, Bartsevich VV, Meng XD, Rupniewski I, Gopalan SM, Sun HC, Pitz KJ, Rock JM, Zhang L, Davis GD, Rebar EJ, Cheeseman IM, Yamamoto KR, Sabatini DM, Jaenisch R, Gregory PD, Urnov FD. 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, 2010, 20(8): 1133-1142.[49] Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, DeKelver RC, Katibah GE, Amora R, Boydston EA, Zeitler B, Meng XD, Miller JC, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jaenisch R. Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol, 2009, 27(9): 851-857.[50] Takasu Y, Kobayashi I, Beumer K, Uchino K, Sezutsu H, Sajwan S, Carroll D, Tamura T, Zurovec M. Targeted mutagenesis in the silkworm Bombyx mori using zinc finger nuclease mRNA injection. Insect Biochem Mol Biol, 2010, 40(10): 759-765.[51] Watanabe M, Umeyama K, Matsunari H, Takayanagi S, Haruyama E, Nakano K, Fujiwara T, Ikezawa Y, Nakauchi H, Nagashima H. Knockout of exogenous EGFP gene in porcine somatic cells using zinc-finger nucleases. Biochem Biophys Res Commun, 2010, 402(1): 14-18.[52] Galli C, Perota A, Brunetti D, Lagutina I, Lazzari G, Lucchini F. Genetic engineering including superseding microinjection: new ways to make GM pigs. Xenotransplantation, 2010, 17(6): 397-410.[53] Lombardo A, Genovese P, Beausejour CM, Colleoni S, Lee YL, Kim KA, Ando D, Urnov FD, Galli C, Gregory PD, Holmes MC, Naldini L. Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat Biotechnol, 2007, 25(11): 1298-1306.[54] Zou JZ, Maeder ML, Mali P, Pruett-Miller SM, Thibodeau-Beganny S, Chou BK, Chen GB, Ye ZH, Park IH, Daley GQ, Porteus MH, Joung JK, Cheng LZ. Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell, 2009, 5(1): 97-110.[55] Del Prete GQ, Haggarty B, Leslie GJ, Jordan APO, Romano J, Wang N, Wang JB, Holmes MC, Montefiori DC, Hoxie JA. Derivation and characterization of a simian immunodeficiency virus SIVmac239 variant with tropism for CXCR4. J Virol, 2009, 83(19): 9911-9922.[56] Doyon Y, Vo TD, Choi VM, Gregory PD, Holmes MC, Xia DF. A transient cold shock enhances zinc-finger nuclease-mediated gene disruption. Nat Methods, 2010, 7(6): 459-460.[57] Greenwald DL, Cashman SM, Kumar-Singh R. Engineered zinc finger nuclease-mediated homologous recombination of the human rhodopsin gene. Invest Ophthalmol Vis Sci, 2010, 51(12): 6374-6380.[58] Doyon JB, Zeitler B, Cheng J, Cheng AT, Cherone JM, Santiago Y, Lee AH, Vo TD, Doyon Y, Miller JC, Paschon DE, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Drubin DG. Rapid and efficient clathrin-mediated endocytosis revealed in genome-edited mammalian cells. Nat Cell Biol, 2011, 13(3): 331-337.[59] Kim S, Lee MJ, Kim H, Kang M, Kim JS. Preassembled zinc-finger arrays for rapid construction of ZFNs. Nat Methods, 2011, 8(1): 7.[60] Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S, Dewell S, Law M, Guo XY, Li X, Wen DC, Chapgier A, DeKelver RC, Miller JC, Lee YL, Boydston EA, Holmes MC, Gregory PD, Greally JM, Rafii S, Yang CW, Scambler PJ, Garrick D, Gibbons RJ, Higgs DR, Cristea IM, Urnov FD, Zheng DY, Allis CD. Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell, 2010, 140(5): 678-691.[61] Carbery ID, Ji DN, Harrington A, Brown V, Weinstein EJ, Liaw L, Cui XX. Targeted genome modification in mice using zinc-finger nucleases. Genetics, 2010, 186(2): 451-459.[62] Meyer M, de Angelis MH, Wurst W, Kühn R. Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases. Proc Natl Acad Sci USA, 2010, 107(34): 15022-15026.[63] Mashimo T, Takizawa A, Voigt B, Yoshimi K, Hiai H, Kuramoto T, Serikawa T. Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases. PLoS ONE, 2010, 5(1): e8870.[64] Ménoret S, Iscache AL, Tesson L, Rémy S, Usal C, Osborn MJ, Cost GJ, Brüggemann M, Buelow R, Anegon I. Characterization of immunoglobulin heavy chain knockout rats. Eur J Immunol, 2010, 40(10): 2932-2941.[65] Moreno C, Hoffman M, Stodola TJ, Didier DN, Lazar J, Geurts AM, North PE, Jacob HJ, Greene AS. Creation and characterization of a Renin knockout rat. Hypertension, 2011, 57(3): 614-619.[66] Santiago Y, Chan E, Liu PQ, Orlando S, Zhang L, Urnov FD, Holmes MC, Guschin D, Waite A, Miller JC, Rebar EJ, Gregory PD, Klug A, Collingwood TN. Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases. Proc Natl Acad Sci USA, 2008, 105(15): 5809-5814.[67] Liu PQ, Chan EM, Cost GJ, Zhang L, Wang JB, Miller JC, Guschin DY, Reik A, Holmes MC, Mott JE, Collingwood TN, Gregory PD. Generation of a triple-gene knockout mammalian cell line using engineered zinc-finger nucleases. Biotechnol Bioeng, 2010, 106(1): 97-105.[68] Malphettes L, Freyvert Y, Chang J, Liu PQ, Chan E, Miller JC, Zhou Z, Nguyen T, Tsai C, Snowden AW, Collingwood TN, Gregory PD, Cost GJ. Highly efficient deletion of FUT8 in CHO cell lines using zinc-finger nucleases yields cells that produce completely nonfucosylated antibodies. Biotechnol Bioeng, 2010, 106(5): 774-783.[69] Cost GJ, Freyvert Y, Vafiadis A, Santiago Y, Miller JC, Rebar E, Collingwood TN, Snowden A, Gregory PD. BAK and BAX deletion using zinc-finger nucleases yields apoptosis-resistant CHO cells. Biotechnol Bioeng, 2010, 105(2): 330-340.[70] Gupta A, Meng XD, Zhu LJ, Lawson ND, Wolfe SA. Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases. Nucleic Acids Res, 2011, 39(1): 381-392.[71] Siekmann AF, Standley C, Fogarty KE, Wolfe SA, Lawson ND. Chemokine signaling guides regional patterning of the first embryonic artery. Genes Dev, 2009, 23(19): 2272-2277.[72] Ochiai H, Fujita K, Suzuki K, Nishikawa M, Shibata T, Sakamoto N, Yamamoto T. Targeted mutagenesis in the sea urchin embryo using zinc-finger nucleases. Genes Cells, 2010, 15(8): 875-885.[73] Beumer K, Bhattacharyya G, Bibikova M, Trautman JK, Carroll D. Efficient gene targeting in Drosophila with zinc-finger nucleases. Genetics, 2006, 172(4): 2391-2403.[74] Beumer KJ, Trautman JK, Bozas A, Liu JL, Rutter J, Gall JG, Carroll D. Efficient gene targeting in Drosophila by direct embryo injection with zinc-finger nucleases. Proc Natl Acad Sci USA, 2008, 105(50): 19821-19826.[75] Zhang F, Maeder ML, Unger-Wallace E, Hoshaw JP, Reyon D, Christian M, Li XH, Pierick CJ, Dobbs D, Peterson T, Joung JK, Voytas DF. High frequency targeted mutagenesis in Arabidopsis thaliana using zinc finger nucleases. Proc Natl Acad Sci USA, 2010, 107(26): 12023-12028.[76] Osakabe K, Osakabe Y, Toki S. Site-directed mutagenesis in Arabidopsis using custom-designed zinc finger nucleases. Proc Natl Acad Sci USA, 2010, 107(26): 12034-12039.[77] Townsend JA, Wright DA, Winfrey RJ, Fu FL, Maeder ML, Joung JK, Voytas DF. High-frequency modification of plant genes using engineered zinc-finger nucleases. Nature, 2009, 459(7245): 442-445.[78] Cai CQ, Doyon Y, Ainley WM, Miller JC, DeKelver RC, Moehle EA, Rock JM, Lee YL, Garrison R, Schulenberg L, Blue R, Worden A, Baker L, Faraji F, Zhang L, Holmes MC, Rebar EJ, Collingwood TN, Rubin-Wilson B, Gregory PD, Urnov FD, Petolino JF. Targeted transgene integration in plant cells using designed zinc finger nucleases. Plant Mol Biol, 2009, 69(6): 699-709.[79] Shukla VK, Doyon Y, Miller JC, DeKelver RC, Moehle EA, Worden SE, Mitchell JC, Arnold NL, Gopalan S, Meng XD, 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. Precise genome modification in the crop species Zea mays using zinc-finger nucleases. Nature, 2009, 459(7245): 437-441 |
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| [15] | 黄骥，张红生. TFⅢA型锌指蛋白及在提高植物耐逆性中的作用[J]. 遗传, 2007, 29(8): 915-922. |
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