非人灵长类基因修饰模型研究进展

Advance of gene-modified non-human-primate models

摘要:

非人灵长类动物在生命科学基础研究和生物医药研究领域具有非常重要的地位。近年来随着慢病毒载体转染及靶向核酸酶 (ZFN，TALEN，CRISPR/Cas9) 等基因操作技术的出现，科学家们成功地获得了外源基因过表达的转基因猴和目的基因定点切割的基因编辑猴。文中对目前利用慢病毒载体获得转基因猴和利用靶向核酸酶获得基因编辑猴的研究进展进行了综述，并讨论了基因修饰猴的嵌合体现象、脱靶现象及非人灵长类动物较长性成熟时间这几个影响非人灵长类基因修饰模型推广应用的因素，最后展望了非人灵长类基因修饰模型构建技术的研究热点及发展趋势。

关键词:非人灵长类，基因修饰，慢病毒载体，靶向核酸酶

Abstract:

Non-human-primates would be particularly valuable in life sciences and biomedical research area. Gene-modified monkeys with gene overexpression or loss of function have been successfully generated with the rapid advance in gene manipulation technology such as lentivirus infection and programmable nucleases (ZFN, TALEN, CRISPR-Cas9). Here we review the recent development on gene-modified monkey generation by lentivirus and programmable nucleases. Then we discuss three concerns, the long time for sexual maturation, the off target and the mosaicism of founders, which limit the wide application of gene-modified non-human-primates. At last, hotspots and future trend for gene-modified non-human-primates generation are proposed.

Key words:non-human-primate, gene-modified, lentivirus, programmable nucleases