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Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9

by Wang, Shouqi , Zhao, Hong-Ye , Kan, Yinan , Wang, Gang , Luo, Yonglun , Wang, Tao , Wei, Hong-Jiang , Wang, Yong , Wei, Hong , Lin, Lin , Niu, Dong , Jiao, Deling , Zhou, Xiaoyang , Shrock, Ellen , Lesha, Emal , Zhao, Heng , Church, George M. , Lee, I-Hsiu , Güell, Marc , Qing, Yubo , George, Haydy , Yang, Luhan

in Animals / CRISPR / CRISPR-Cas Systems / Deactivation / Disease Transmission, Infectious - prevention & control / Endogenous retroviruses / Endogenous Retroviruses - genetics / Gene Editing - methods / Genome editing / Genomes / HEK293 Cells / Hogs / Horizontal transfer / Humans / Immunology / Inactivation / Nuclear safety / Nuclear transfer / Organs / Retroviridae Infections - transmission / Shortages / Somatic cell nuclear transfer / Sus scrofa - genetics / Sus scrofa - virology / Swine / Transplantation / Transplantation, Heterologous - adverse effects / Transplants / Transplants & implants / Xenografts / Xenotransplantation

2017

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Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9

2017

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Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9

2017

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Journal Article

Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9

Wang, Shouqi,

Zhao, Hong-Ye,

Kan, Yinan,

Wang, Gang,

Luo, Yonglun,

Wang, Tao,

Wei, Hong-Jiang,

Wang, Yong,

Wei, Hong,

Lin, Lin,

Niu, Dong,

Jiao, Deling,

Zhou, Xiaoyang,

Shrock, Ellen,

Lesha, Emal,

Zhao, Heng,

Church, George M.,

Lee, I-Hsiu,

Güell, Marc,

Qing, Yubo,

George, Haydy,

Yang, Luhan

2017

Overview

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.

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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

Animals

/ CRISPR

/ CRISPR-Cas Systems

/ Deactivation

/ Disease Transmission, Infectious - prevention & control

/ Endogenous retroviruses

/ Endogenous Retroviruses - genetics