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    席龙昌, 葛治伸. 非病毒基因编辑CRISPR/Cas9递送载体的研究进展[J]. 功能高分子学报, 2019, 32(5): 582-592. doi: 10.14133/j.cnki.1008-9357.20190426001
    引用本文: 席龙昌, 葛治伸. 非病毒基因编辑CRISPR/Cas9递送载体的研究进展[J]. 功能高分子学报, 2019, 32(5): 582-592. doi: 10.14133/j.cnki.1008-9357.20190426001
    XI Longchang, GE Zhishen. Nonviral CRISPR/Cas9 Delivery Systems for Gene Editing[J]. Journal of Functional Polymers, 2019, 32(5): 582-592. doi: 10.14133/j.cnki.1008-9357.20190426001
    Citation: XI Longchang, GE Zhishen. Nonviral CRISPR/Cas9 Delivery Systems for Gene Editing[J]. Journal of Functional Polymers, 2019, 32(5): 582-592. doi: 10.14133/j.cnki.1008-9357.20190426001

    非病毒基因编辑CRISPR/Cas9递送载体的研究进展

    Nonviral CRISPR/Cas9 Delivery Systems for Gene Editing

    • 摘要: 基因编辑技术是指能对目标基因片段进行编辑,包括敲除、敲入等。近年来,基因编辑技术得到了很大的发展,包括规律成簇的间隔短回文重复序列(CRISPR)/CRISPR相关蛋白9(Cas9)在内的一系列基因编辑技术受到了广泛的关注。CRISPR/Cas9主要利用限制性内切酶,在蛋白或RNA的引导下,使目标位置的DNA双链断裂,在治疗基因表达异常引起的疾病方面表现出了巨大的潜力。应用这项技术进行基因编辑的关键点之一是,必须要将相关的蛋白或核酸高效地递送到细胞核中。相对于病毒载体,非病毒载体在安全性及规模化生产方面表现出了更高的优越性,是目前基因编辑递送载体发展的重点。本文对近期基因编辑CRISPR/Cas9非病毒递送载体的重要进展进行综述,介绍了非病毒载体的优势,在非病毒载体体系中,着重介绍脂质体和高分子载体在CRISPR/Cas9技术应用中的近期进展,并展望了非病毒CRISPR/Cas9递送载体在未来的发展方向。

       

      Abstract: Gene editing technologies refer to a type of gene engineering to inactivate genes, correct mutated sequences, or insert intact genes. Great progresses in the gene editing tools, including clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9), have been made in recent years. A short single guide RNA (sgRNA) with the sequences that can bind to a specific target sequence of DNA and also bind to the Cas9 enzyme has been used to guide Cas9 to cut the DNA at the targeted location and induce the breakage of double-strand DNA, showing great potentials for the treatment of many diseases. Efficient delivery of CRISPR/Cas9 into the cells is the key to improve the gene editing efficiency. Viral CRISPR/Cas9 delivery systems have been widely used in the studies and clinical translation of CRISPR/Cas9-based gene editing. Although all viral vector genomes have been modified by removing some areas in the genomes so that the replication becomes deranged and thereby makes the virus be safer, some critical problems still exist, such as the immunogenicity that may cause inflammatory, toxin production, and the limitation in transgenic capacity size. Relative to viral delivery systems, nonviral delivery systems possess significant advantages in biosafety and large-scale production, which have attracted great attention for the delivery of CRISPR/Cas9. Indeed, great progresses in nonviral CRISPR/Cas9 delivery systems have been made in recent years. Various efficient biodegradable and biocompatible systems have been developed for in vitro and in vivo applications. In this review, the advantages of nonviral delivery systems compared to the typical viral delivery systems were discussed, and then the recent progresses in lipid and polymer delivery systems were primarily summarized. Among them, the representative examples were discussed in detail. Finally, the conclusions and perspectives concerning the obstacles of nonviral CRISPR/Cas9 delivery systems as well as further development direction were proposed.

       

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