《生命科学》 2018, 30(9): 955-966
摘 要:摘 要:猪不仅具有重要的农业生产价值,由于猪繁殖周期比灵长类动物短,产仔量多,以及猪器官大小、生理代谢过程和解剖结构,尤其是心血管系统及神经系统较啮齿类动物而言与人类更为接近,猪在生物医药领域也具有重要的用途。对猪基因组加以编辑,在农业上可以加速高生产性能猪新品种的培育;在生命科学领域可用于基因功能、胚胎发育及代谢过程等基础研究;在医学上,可提供与人体更为匹配的异种移植器官,可作为更能准确模拟人类疾病的大动物模型,用于新的药物和治疗手段的开发。人工核酸酶的出现,使基因编辑效率得到大大提高,克服了原有的基因编辑猪制备困难、成功率极低的问题。人工核酸酶技术不仅在猪上实现了高效而又精确的基因编辑,并且使各种基因突变模式,如基因敲除、基因敲入、基因组无痕点突变、多基因编辑、体内直接基因编辑以及条件性基因编辑等都成为可能。现将对利用不同人工核酸酶技术结合不同的基因编辑策略建立基因编辑猪的研究新进展进行综述。
Abstract: Abstract: Pigs not only have important agricultural value, but also play an important role in the field of biomedicine because of their shorter reproduction cycle and larger litter size comparing with that of the primate, as well as more similarity of organ size, physiology, metabolism and anatomy, to human comparing with the rodent, especially in cardiovascular system and nervous system. The genome editing of pigs can be used to breed new strain of pigs with higher productivity in agriculture, to study gene function, development of embryos and metabolism in basic life science field and to provide organs for xenotransplantation, human disease models for developing new drug and new therapeutic strategies in medical field. With the newly emerged engineered endonuclease with high gene editing efficiency, the difficulty of the genome editing has been overcome. The engineered endonucleases not only make pig gene editing with high efficiency and accuracy, but also can be used to generate a variety of gene mutation patterns including knock out, knock in, seamless point mutation, multiple gene editing, direct gene editing in vivo,as well as conditional gene-editing in pigs. Here, we will provide an overview of the advances in generation of gene-editing pigs with different gene editing strategies.