Genome-wide inactivation of porcine endogenous retroviruses (PERVs)

被引：507

作者：

Yang, Luhan ^{[1
,2
,3
]}

Gueell, Marc ^{[1
,2
,3
]}

Niu, Dong ^{[1
,4
]}

George, Haydy ^{[1
]}

Lesha, Emal ^{[1
]}

Grishin, Dennis ^{[1
]}

Aach, John ^{[1
]}

Shrock, Ellen ^{[1
]}

Xu, Weihong ^{[6
]}

Poci, Juergen ^{[1
]}

Cortazio, Rebeca ^{[1
]}

Wilkinson, Robert A. ^{[5
]}

Fishman, Jay A. ^{[5
]}

Church, George ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02138 USA

[2] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA

[3] eGenesis Biosci, Boston, MA 02115 USA

[4] Zhejiang Univ, Coll Anim Sci, Hangzhou 310058, Zhejiang, Peoples R China

[5] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA

来源：

SCIENCE | 2015年 / 350卷 / 6264期

关键词：

HUMAN-CELLS; TRANSGENIC PIGS; NO EVIDENCE; XENOTRANSPLANTATION; INFECTION; DNA;

D O I：

10.1126/science.aad1191

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERV copy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a >1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation.

引用

页码：1101 / 1104

页数：5

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