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https://hdl.handle.net/2440/120427
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Type: | Journal article |
Title: | Xenogeneic transplantation and tolerance in the era of CRISPR-Cas9 |
Author: | Cowan, P.J. Hawthorne, W.J. Nottle, M.B. |
Citation: | Current Opinion in Organ Transplantation, 2019; 24(1):5-11 |
Publisher: | Wolters Kluwer |
Issue Date: | 2019 |
ISSN: | 1087-2418 1531-7013 |
Statement of Responsibility: | Peter J. Cowan, Wayne J. Hawthorne and Mark B. Nottle |
Abstract: | 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, β4GALNT2, 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. |
Keywords: | CRISPR-Cas9; knock-in; knockout; xenotransplantation |
Rights: | Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. |
DOI: | 10.1097/mot.0000000000000589 |
Grant ID: | NHMRC |
Published version: | http://dx.doi.org/10.1097/mot.0000000000000589 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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