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簇状规律间隔短回文重复序列/ Cas9 基因编辑技术在异种移植中的应用。

Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Gene Editing Technique in Xenotransplantation.

机构信息

The Childhood Cancer Center at Nationwide Children's Hospital, Columbus, OH, United States.

Department of Basic Science of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.

出版信息

Front Immunol. 2018 Sep 5;9:1711. doi: 10.3389/fimmu.2018.01711. eCollection 2018.

Abstract

Genetically modified pigs have been considered favorable resources in xenotransplantation. Microinjection of randomly integrating transgenes into zygotes, somatic cell nuclear transfer, homologous recombination, zinc finger nucleases, transcription activator-like effector nucleases, and most recently, clustered regularly interspaced short palindromic repeats-cas9 (CRISPR/Cas9) are the techniques that have been used to generate these animals. Here, we provide an overview of the CRISPR approaches that have been used to modify genes which are vital in improving xenograft survival rate, including cytidine monophosphate--acetylneuraminic acid hydroxylase, B1,4N-acetylgalactosaminyltransferase, isoglobotrihexosylceramide synthase, class I MHC, von Willebrand factor, C3, and porcine endogenous retroviruses. In addition, we will mention the importance of potential candidate genes which could be targeted using CRISPR/Cas9.

摘要

基因修饰猪一直被认为是异种移植的有利资源。将随机整合的转基因微注射到受精卵、体细胞核移植、同源重组、锌指核酸酶、转录激活因子样效应物核酸酶,以及最近的 CRISPR/Cas9(成簇规律间隔短回文重复),是用于生成这些动物的技术。在这里,我们提供了一个概述,介绍了用于修饰基因的 CRISPR 方法,这些基因对于提高异种移植物存活率至关重要,包括胞苷单磷酸-N-乙酰神经氨酸羟化酶、B1,4N-乙酰半乳糖胺基转移酶、异球蛋白三己糖神经酰胺合酶、I 类 MHC、血管性血友病因子、C3 和猪内源性逆转录病毒。此外,我们还将提到使用 CRISPR/Cas9 可以靶向的潜在候选基因的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/962c/6134075/3407e5438ef3/fimmu-09-01711-g001.jpg

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