锌指蛋白核酸酶的作用原理及其应用

doi:锌指结构域; 锌指蛋白; 锌指蛋白核酸酶; 同源重组; 基因打靶

遗传 ›› 2011, Vol. 33 ›› Issue (2): 123-130.doi: 锌指结构域; 锌指蛋白; 锌指蛋白核酸酶; 同源重组; 基因打靶

锌指蛋白核酸酶的作用原理及其应用

钟强, 赵书红

华中农业大学农业动物遗传育种与繁殖教育部重点实验室, 农业部猪遗传育种重点开放实验室, 武汉 430070

收稿日期:2010-07-01 修回日期:2010-11-07 出版日期:2011-02-20 发布日期:2011-02-25
通讯作者: 赵书红 E-mail:shzhao@mail.hzau.edu.cn
基金资助:
国家转基因重大专项与教育部创新团队项目(编号：IRT0831)资助

The mechanism and application of zinc finger nucleases

ZHONG Qiang , ZHAO Shu-Hong

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China

Received:2010-07-01 Revised:2010-11-07 Online:2011-02-20 Published:2011-02-25
Contact: ZHAO Shu-Hong E-mail:shzhao@mail.hzau.edu.cn

摘要/Abstract

摘要： 锌指蛋白核酸酶(Zinc finger nucleases, ZFN)因其能特异性识别并切割DNA序列以及可设计性, 被用于基因定点突变和外源基因定点整合。目前, ZFN技术以其准确的靶位点设计能力和诱发高效率基因打靶的优势, 越来越受到基因改造研究者的重视, 已经成功应用于动植物细胞、胚胎的基因改造。随着鉴定靶DNA高亲和力的锌指蛋白(Zinc finger protein, ZFP)实验技术日渐成熟, 可以预见到不久的将来这项技术会在基因工程和育种中得到广泛应用。文章介绍了锌指蛋白识别DNA靶位点和ZFN介导的基因打靶(Double strand break gene targeting, DSB-GT)的原理, 同时还综述了目前ZFN技术用于基因改造的研究进展。

关键词: 锌指结构域, 锌指蛋白, 锌指蛋白核酸酶, 同源重组, 基因打靶

Abstract: Due to specific recognization of DNA sequences and designability, zinc finger nucleases (ZFN) has been used in knock in and knock out genes. Because of high ratio of homologous recombination of DSB-GT induces by ZFN, ZFN technology has been considered as the most powerful tool for gene modification. It has been successfully used at cell or embryo levels in plants and animals. Under the rapid development of high affinity zinc finger protein (ZFP), this technique will be applied to genetic engineering and breeding extensively in the future. This review discussed the DNA recognization mechanism and double strand break gene targeting (DSB-GT) of zinc finger nucleases (ZFN). Some application examples of ZFN were summarized.

Key words: zinc finger domain, zinc finger protein, zinc finger nucleases, homologous recombination, gene targeting

钟强，赵书红. 锌指蛋白核酸酶的作用原理及其应用[J]. 遗传, 2011, 33(2): 123-130.

ZHONG Jiang, DIAO Shu-Gong. The mechanism and application of zinc finger nucleases[J]. HEREDITAS, 2011, 33(2): 123-130.

参考文献

[1] Jasin M. Genetic manipulation of genomes with rare-cutting endonucleases. Trends Genet, 1996, 12(6): 224-228.

[2] Liang F, Han MG, Romanienko PJ, Jasin M. Homology-directed repair is a major double-strand break repair pathway in mammalian cells. Proc Natl Acad Sci USA, 1998, 95(9): 5172-5177.

[3] 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.

[4] 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.

[5] 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.

[6] Foley JE, Yeh JRJ, Maeder ML, Reyon D, Sander JD, Peterson RT, Joung JK. Rapid mutation of endogenous ze-brafish genes using zinc finger nucleases made by Oli-gomerized Pool ENgineering (OPEN). PLoS One, 2009, 4(2): e4348.

[7] Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, DeKelver RC, Katibah GE, Amora R, Boydston EA, Zeit-ler 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.

[8] 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.

[9] Maeder ML, Thbodeau-Beganny S, Osiak A, Wright DA, Anthony RM, Eichtinger M, Jaing T, Foley JE, Winfrey RJ, Townsend JA, Unger-Wallance 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.

[10] 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.

[11] Sander JD, Zaback PZ, Joung JK, Voytas DF, Dobbs D. Zinc Finger Targeter (ZiFiT): an engineered zinc fin-ger/target site design tool. Nucleic Acids Res, 2007, 35(Suppl. 2): W599-W605.

[12] Jantz D, Berg J M. Probing the DNA-binding affinity and specificity of designed zinc finger proteins. Biophys J, 2010, 98(5): 852-860.

[13] Cornu TI, Thibodeau-Beganny S, Guhl E, Alwin S, Eicht-inger M, Joung JK, Cathomen T. DNA-binding specificity is a major determinant of the activity and toxicity of zinc-finger nucleases. Mol Ther, 2007, 16(2): 352-358.

[14] Liu JJ, Stormo GD. Context-dependent DNA recognition code for C2H2 zinc-finger transcription factors. Bioinfor-matics, 2008, 24(17): 1850-1857.

[15] Liu LA, Bader JS. Structure-based ab initio prediction of transcription factor-binding sites. Methods Mol Biol, 2009, 541: 23-41.

[16] Temiz NA, Camacho CJ. Experimentally based contact energies decode interactions responsible for protein-DNA affinity and the role of molecular waters at the binding in-terface. Nucleic Acids Res, 2009, 37(12): 4076-4088.

[17] 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.

[18] Klug A. The discovery of zinc fingers and their applica-tions in gene regulation and genome

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锌指蛋白核酸酶的作用原理及其应用

The mechanism and application of zinc finger nucleases

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