具有可控基因表达元件的基因组编辑猪模型

Qin Jin, Hui Shi, Xiaoyi Liu, Jialu Ju, Kepin Wang, Liangxue Lai
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摘要

条件基因调控系统可以控制基因在预定组织或器官中的表达。位点特异性重组酶系统和化学诱导基因表达系统是两种最广泛使用的方法,用于创造基因表达有条件调节的转基因动物。由于缺乏生殖系能多能干细胞,具有可控元素的转基因猪的产生(通常涉及多个基因编辑)过去是一个主要挑战。随着人工核酸内切酶介导的基因编辑器的出现,通过结合体细胞的定点敲入和体细胞核转移技术,已经产生了多种具有重组酶特异性识别元件或化学诱导元件的基因表达条件调控的转基因猪,允许猪有条件地删除内源基因或过表达外源基因。这些诱导工具猪模型将极大地促进转基因猪的生产,拓宽转基因猪在生物医药和农业领域的应用。本文就利用基因编辑技术构建具有可控元件的猪及其应用进展进行综述。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Genome editing pig models with elements for controllable gene expression

Conditional gene regulation systems can control gene expression in predefined tissues or organs at a desired time. Site-specific recombinase systems and chemically induced gene expression systems are the two most widely used approaches for creating genetically modified (GM) animals with conditional regulation of gene expression. Generation of GM pigs with controllable elements, usually involving multiple gene editing, used to be a major challenge due to a lack of germ line-competent pluripotent stem cells. With the emergence of artificial endonuclease-mediated gene editors, a variety of GM pigs with recombinase-specific recognition elements or chemically induced elements for conditional regulation of gene expression have been generated by the combination of site-directed knock-in of somatic cells and somatic cell nuclear transfer technology, allowing conditional deletion of endogenous genes or overexpression of exogenous genes in pigs. These inducible tool pig models will greatly facilitate the production of GM pigs and broaden the applications of transgenic pigs in biomedicine and agriculture fields. In this paper, we review the progress in the construction and application of pigs with controllable elements using gene editing techniques.

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