动物基因组定点整合转基因技术研究进展

发布时间：2018-08-26 21:06

【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。
[Abstract]:Traditional transgenic techniques, such as microinjection, transposon, and lentivirus transfection, are random in the integration of target genes into the genome. These random integrations are detrimental to strain formation and breeding of late transgenic animals. Therefore, some researchers have proposed a targeted integration of transgenic technology. At present, the efficiency of fixed-point integration is very low, which mainly depends on two aspects: first, the efficiency of DNA double-strand break (double-strand break,DSB) produced by target sites; The second is the efficiency of homologous recombination between the target sites and donor plasmids carrying homologous arms and foreign genes. Homologous recombination repair of (homologous recombination repair,HDR) is the most dependent repair mechanism of genomic site-directed integration. After the target site produces DSB, the DNA repair of the body may occur both HDR, and non-homologous terminal junction (nonhomologous end joining,NHEJ), and there is a competitive relationship between the two. Therefore, activation of HDR or inhibition of NEHJ can improve the efficiency of site-directed integration. This paper reviews the latest exploration of improving the efficiency of fixed-point integration.
【作者单位】：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;广东温氏食品集团股份有限公司;
【基金】：国家转基因重大专项(编号:2016ZX08006002) 粤西“扬帆计划”博士后人才扶持基金资助项目(2015)资助~~
【分类号】：Q78

【相似文献】