非病毒纳米载体递送CRISPR/Cas9的研究进展

Research Progress on Non-viral Nanocarrier Delivery of CRISPR/Cas9

成簇规则间隔的短回文重复序列及其相关蛋白9(clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9,CRISPR/Cas9)技术目前广泛应用于生命医学领域的基础研究及临床应用研究。由于载体在CRISPR/Cas9技术中发挥了重要的作用,如何进一步开发和优化载体系统具有重要的意义。传统的载体大多以病毒载体为主,其递送的效率高,但亦存在插入片段的大小有限、免疫反应、致癌、难以大规模生产甚至脱靶等缺陷;而非病毒纳米载体在一定程度上可解决基因编辑过程中由病毒载体所带来的潜在毒性和容量限制等问题,可能具有更广阔的应用前景。本文主要综述了目前用于CRISPR/Cas9系统递送的非病毒纳米载体,探讨了非病毒纳米载体在递送CRISPR/Cas9系统时可能遇到的主要困难,提出了相应的解决方案和策略,以期为基因治疗和药物研发提供新的参考依据。

Clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9(CRISPR/Cas9)technology is currently widely used in both basic and clinical application research of medicine.Since vectors play an important role in CRISPR/Cas9 technology,further developing and optimizing vector systems is of great significance.Most of the traditional vectors are viral vectors,which have high delivery efficiency,but with defects such as limited insert size,induction of immune response,carcinogenicity,difficulty in largescale production and even off-target.Non-viral nanocarriers can solve,to some extent,the potential toxicity and capacity limitations caused by viral vectors during gene editing,and may have broader application prospects.This paper reviews the non-viral nanocarriers currently used for CRISPR/Cas9 system delivery,including main difficulties that non-viral nanocarriers may encounter in delivering CRISPR/Cas9 systems,and corresponding solutions and strategies,in order to provide a new reference for gene therapy and drug development.