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用于 CRISPR/Cas9 基因组编辑的 Cas9 核糖核蛋白递送策略。

Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editing.

机构信息

South China Advanced Institute for Soft Matter Science and Technology, School of Molecular Science and Engineering, South China University of Technology, Guangzhou 510640, China.

The Second People's Hospital of Taizhou affiliated to Yangzhou University, Taizhou, 225500, China.

出版信息

Theranostics. 2021 Jan 1;11(2):614-648. doi: 10.7150/thno.47007. eCollection 2021.

Abstract

CRISPR/Cas9 genome editing has gained rapidly increasing attentions in recent years, however, the translation of this biotechnology into therapy has been hindered by efficient delivery of CRISPR/Cas9 materials into target cells. Direct delivery of CRISPR/Cas9 system as a ribonucleoprotein (RNP) complex consisting of Cas9 protein and single guide RNA (sgRNA) has emerged as a powerful and widespread method for genome editing due to its advantages of transient genome editing and reduced off-target effects. In this review, we summarized the current Cas9 RNP delivery systems including physical approaches and synthetic carriers. The mechanisms and beneficial roles of these strategies in intracellular Cas9 RNP delivery were reviewed. Examples in the development of stimuli-responsive and targeted carriers for RNP delivery are highlighted. Finally, the challenges of current Cas9 RNP delivery systems and perspectives in rational design of next generation materials for this promising field will be discussed.

摘要

近年来,CRISPR/Cas9 基因组编辑技术受到了越来越多的关注,然而,将这项生物技术转化为治疗方法一直受到将 CRISPR/Cas9 材料有效递送到靶细胞的阻碍。由于 Cas9 蛋白和单指导 RNA(sgRNA)组成的核糖核蛋白(RNP)复合物的直接递送具有瞬时基因组编辑和减少脱靶效应的优势,因此已成为一种强大而广泛的基因组编辑方法。在这篇综述中,我们总结了当前的 Cas9 RNP 递送系统,包括物理方法和合成载体。综述了这些策略在细胞内 Cas9 RNP 递送上的作用机制和有益作用。强调了用于 RNP 递送的刺激响应和靶向载体的开发实例。最后,讨论了当前 Cas9 RNP 递送系统的挑战以及对这一有前途领域下一代材料进行合理设计的展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be4/7738854/2e2013711ca3/thnov11p0614g001.jpg

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