期刊
CURRENT OPINION IN ORGAN TRANSPLANTATION
卷 24, 期 1, 页码 5-11出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOT.0000000000000589
关键词
CRISPR-Cas9; knock-in; knockout; xenotransplantation
资金
- National Health and Medical Research Council (NHMRC) of Australia
- Juvenile Diabetes Research Foundation (JDRF)
Purpose of review The use of genetically modified donor pigs has been integral to recent major advances in xenograft survival in preclinical nonhuman primate models. CRISPR-Cas9 gene editing technology has dramatically accelerated the development of multimodified pigs. This review examines the current and projected impact of CRISPR-Cas9-mediated donor modification on preventing rejection and potentially promoting tolerance of porcine xenografts. Recent findings CRISPR-Cas9 has been used to engineer several genetic modifications relevant to xenotransplantation into pigs, including glycosyltransferase knockouts (GGTA1, CMAH, beta 4GALNT2, A3GALT2 and combinations thereof), other knockouts (SLA-I, ULBP1, PERV and GHR), and one knock-in (anti-CD2 monoclonal antibody transgene knocked into GGTA1). Although the use of these pigs as donors in preclinical nonhuman primate models has been limited to a single study to date, in-vitro analysis of their cells has provided invaluable information. For example, deletion of three of the glycosyltransferases progressively decreased the binding and cytotoxicity of preexisting immunoglobulin G and immunoglobulin M in human sera, suggesting that this 'triple-KO' pig could be a platform for clinical xenotransplantation. Summary CRISPR-Cas9 enables the rapid generation of gene-edited pigs containing multiple tailored genetic modifications that are anticipated to have a positive impact on the efficacy and safety of pig-to-human xenotransplantation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据