Yao Jing, Huang Jiaojiao, Zhao Jianguo
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Hum Genet. 2016 Sep;135(9):1093-105. doi: 10.1007/s00439-016-1710-6. Epub 2016 Jul 18.
Pigs have anatomical, physiological and genomic characteristics that make them highly suitable for modeling human diseases. Genetically modified (GM) pig models of human diseases are critical for studying pathogenesis, treatment, and prevention. The emergence of nuclease-mediated genome editing technology has been successfully employed for engineering of the pig genome, which has revolutionize the creation of GM pig models with highly complex pathophysiologies and comorbidities. In this review, we summarize the progress of recently developed genome editing technologies, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9), which enable highly efficient and precise introduction of genome modifications into pigs, and tailored disease models that have been generated in various disciplines via genome editing technology. We also summarize the GM pig models that have been generated by conventional transgenic strategies. Additionally, perspectives regarding the application of GM pigs in biomedical research are discussed.
猪具有解剖学、生理学和基因组特征,使其非常适合用于人类疾病建模。人类疾病的转基因猪模型对于研究发病机制、治疗和预防至关重要。核酸酶介导的基因组编辑技术的出现已成功用于猪基因组工程,这彻底改变了具有高度复杂病理生理学和合并症的转基因猪模型的创建。在本综述中,我们总结了最近开发的基因组编辑技术的进展,包括锌指核酸酶(ZFNs)、转录激活样效应核酸酶(TALENs)以及成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关蛋白9(Cas9),这些技术能够高效、精确地将基因组修饰引入猪中,以及通过基因组编辑技术在各个学科中生成的定制疾病模型。我们还总结了通过传统转基因策略生成的转基因猪模型。此外,还讨论了转基因猪在生物医学研究中的应用前景。