动物基因组定点整合转基因技术研究进展

doi:10.16288/j.yczz.16-367

遗传 ›› 2017, Vol. 39 ›› Issue (2): 98-109.doi: 10.16288/j.yczz.16-367

动物基因组定点整合转基因技术研究进展

李国玲¹(),钟翠丽¹,莫健新¹,全绒¹,吴珍芳^1,²,李紫聪¹,杨化强^1,²(),张献伟^1,²()

1. 华南农业大学动物科学学院,国家生猪种业工程技术研究中心,广州 510642
2. 广东温氏食品集团股份有限公司,新兴 527439

收稿日期:2016-11-01 修回日期:2017-01-16 出版日期:2017-02-20 发布日期:2017-01-24
作者简介:李国玲,硕士研究生,专业方向：基因编辑。E-mail: 792268184@qq.com|杨化强,博士,副研究员,研究方向：遗传育种。E-mail: Yangh@scau.edu.cn|张献伟,博士,研究方向：遗传育种。E-mail: zxianw@163.com
基金资助:
国家转基因重大专项(2016ZX08006002);粤西“扬帆计划”博士后人才扶持基金资助项目(2015)

Advances in site-specific integration of transgene in animal genome

Li Guoling¹(),Zhong Cuili¹,Mo Jianxin¹,Quan Rong¹,Wu Zhenfang^1,²,Li Zicong¹,Yang Huaqiang^1,²(),Zhang Xianwei^1,²()

1. National Engineering Research Center for Swine Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
2. Guangdong Wens Foodstuff Co., Ltd., Xinxing 527439, China

Received:2016-11-01 Revised:2017-01-16 Online:2017-02-20 Published:2017-01-24
Supported by:
the National Transgenic Major Projects(2016ZX08006002);Yuexi "Flying Sail Program" Postdoctoral Foundation(2015)

摘要/Abstract

摘要：

传统转基因技术,如显微注射、转座子、慢病毒转染等将目的基因插入基因组内的整合方式是随机的,这些随机整合对后期转基因动物品系组建和育种带来诸多不利,因此有研究人员提出了定点整合转基因技术。目前该技术的定点整合效率非常低,主要取决于两个方面：一是靶位点产生DNA双链断裂(double-strand break, DSB)的效率;二是断裂后的靶位点与携带同源臂及外源基因的供体质粒发生同源重组的效率,其中同源重组修复(homologous recombination repair, HDR)是基因组定点整合最为依赖的修复机制。靶位点产生DSB后,机体的DNA修复既可能发生HDR,也可能发生非同源末端连接(nonhomologous end joining, NHEJ),并且两者之间存在竞争关系,因此激活HDR或抑制NEHJ都可提高定点整合转基因的效率。本文结合影响定点整合的因素,对提高定点整合效率最新探索方面进行了综述。

关键词: 同源重组修复, 定点整合, CRISPR/Cas9

Abstract:

The traditional transgenic technologies, such as embryo microinjection, transposon-mediated integration, or lentiviral transfection, usually result in random insertions of the foreign DNA into the host genome, which could have various disadvantages in the establishment of transgenic animals. Therefore, a strategy for site-specific integration of a transgene is needed to generate genetically modified animals with accurate and identical genotypes. However, the efficiency for site-specific integration of transgene is very low, which is mainly caused by two issues. The first one is the low efficiency of inducing double-strand break (DSB) at the target site of host genome in the initial process. The second one is the low efficiency of homologous recombination repair (HDR) between the target site and the donor plasmid carrying homologous arm and foreign genes. HDR is the most common mechanism for site-specific integration of a transgene. DSBs can stimulate DNA repair mainly by two competitive mechanisms, HDR and nonhomologous end joining (NHEJ). Hence, activation of HDR or inhibition of NHEJ can promote the HDR in the integration processes, thereby optimizing a specific targeting of the transgene. In this review, we summarize the recent advances in strategies for improving the site-specific integration of foreign transgene in transgenic technologies.

Key words: homologous recombination repair, site-specific integration, CRISPR/Cas9

李国玲,钟翠丽,莫健新,全绒,吴珍芳,李紫聪,杨化强,张献伟. 动物基因组定点整合转基因技术研究进展[J]. 遗传, 2017, 39(2): 98-109.

Li Guoling,Zhong Cuili,Mo Jianxin,Quan Rong,Wu Zhenfang,Li Zicong,Yang Huaqiang,Zhang Xianwei. Advances in site-specific integration of transgene in animal genome[J]. Hereditas(Beijing), 2017, 39(2): 98-109.

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动物基因组定点整合转基因技术研究进展

Advances in site-specific integration of transgene in animal genome

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