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.

中文翻译：

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使用CRISPR-Cas9灭活猪内源性逆转录病毒

异种移植是减轻人体移植器官短缺的一种有前途的策略。除了担心猪与人之间的免疫相容性外，猪内源性逆转录病毒（PERV）跨物种传播的风险也阻碍了该方法的临床应用。我们先前证明了永生化猪细胞系中灭活PERV活性的可行性。现在，我们确认PERV感染人类细胞，并且观察到PERV在人类细胞之间的水平转移。使用CRISPR-Cas9，我们灭活了猪原代细胞系中的所有PERV，并通过体细胞核转移产生了PERV灭活的猪。