CRISPR/Cas9-Based Genome Editing for Disease Modeling and Therapy: Challenges and Opportunities for Nonviral Delivery,Chemical Reviews

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CRISPR/Cas9-Based Genome Editing for Disease Modeling and Therapy: Challenges and Opportunities for Nonviral Delivery
Chemical Reviews ( IF 51.4 ) Pub Date : 2017-06-22 00:00:00 , DOI: 10.1021/acs.chemrev.6b00799
Hong-Xia Wang ₁ , Mingqiang Li ₁ , Ciaran M. Lee ₂ , Syandan Chakraborty ₁ , Hae-Won Kim ₃ , Gang Bao ₂ , Kam W. Leong ₁

Affiliation

Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology can be used to edit single or multiple genes in a wide variety of cell types and organisms in vitro and in vivo. Herein, we review the rapidly developing CRISPR/Cas9-based technologies for disease modeling and gene correction and recent progress toward Cas9/guide RNA (gRNA) delivery based on viral and nonviral vectors. We discuss the relative merits of delivering the genome editing elements in the form of DNA, mRNA, or protein, and the opportunities of combining viral delivery of a transgene encoding Cas9 with nonviral delivery of gRNA. We highlight the lessons learned from nonviral gene delivery in the past three decades and consider their applicability for CRISPR/Cas9 delivery. We also include a discussion of bioinformatics tools for gRNA design and chemical modifications of gRNA. Finally, we consider the extracellular and intracellular barriers to nonviral CRISPR/Cas9 delivery and propose strategies that may overcome these barriers to realize the clinical potential of CRISPR/Cas9-based genome editing.

中文翻译：

基于CRISPR / Cas9的基因组编辑，用于疾病建模和治疗：非病毒传递的挑战和机遇

基因组编辑通过编辑DNA序列或调节基因表达，为遗传疾病提供了有前途的解决方案。簇状规则间隔的短回文重复序列（CRISPR）/相关蛋白9（CRISPR / Cas9）技术可用于在体外和体内编辑多种细胞类型和生物体中的单个或多个基因。在本文中，我们回顾了快速发展的基于CRISPR / Cas9的疾病建模和基因校正技术，以及基于病毒和非病毒载体的Cas9 /指南RNA（gRNA）传递的最新进展。我们讨论了以DNA，mRNA或蛋白质的形式传递基因组编辑元件的相对优点，以及将编码Cas9的转基因的病毒传递与gRNA的非病毒传递相结合的机会。我们重点介绍了过去三十年来从非病毒基因传递中获得的经验教训，并考虑了它们在CRISPR / Cas9传递中的适用性。我们还讨论了用于gRNA设计和gRNA化学修饰的生物信息学工具。最后，我们考虑了非病毒CRISPR / Cas9传递的细胞外和细胞内障碍，并提出了可以克服这些障碍的策略，以实现基于CRISPR / Cas9的基因组编辑的临床潜力。

更新日期：2017-06-22

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