利用CRISPR-Cas9技术使猪体内的猪内源性逆转录病毒失活。
Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9.
作者信息
Niu Dong, Wei Hong-Jiang, Lin Lin, George Haydy, Wang Tao, Lee I-Hsiu, Zhao Hong-Ye, Wang Yong, Kan Yinan, Shrock Ellen, Lesha Emal, Wang Gang, Luo Yonglun, Qing Yubo, Jiao Deling, Zhao Heng, Zhou Xiaoyang, Wang Shouqi, Wei Hong, Güell Marc, Church George M, Yang Luhan
机构信息
eGenesis, Cambridge, MA 02139, USA.
College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
出版信息
Science. 2017 Sep 22;357(6357):1303-1307. doi: 10.1126/science.aan4187. Epub 2017 Aug 10.
Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concerns about pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. We previously demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. We now confirm that PERVs infect human cells, and we observe the horizontal transfer of PERVs among human cells. Using CRISPR-Cas9, we inactivated all of the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer. Our study highlights the value of PERV inactivation to prevent cross-species viral transmission and demonstrates the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation.
异种移植是缓解人类移植器官短缺的一种有前景的策略。除了对猪与人免疫相容性的担忧外，猪内源性逆转录病毒（PERV）跨物种传播的风险阻碍了这种方法的临床应用。我们之前证明了在永生化猪细胞系中使PERV失活的可行性。我们现在证实PERV可感染人类细胞，并观察到PERV在人类细胞间的水平转移。利用CRISPR-Cas9，我们使猪原代细胞系中的所有PERV失活，并通过体细胞核移植产生了PERV失活猪。我们的研究突出了PERV失活对预防跨物种病毒传播的价值，并证明成功生产出PERV失活动物以解决临床异种移植中的安全问题。
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