Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities.
Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities.
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基于 CRISPR/Cas9 的基因组编辑的非病毒传递系统：挑战和机遇
DOI：
10.1016/j.biomaterials.2018.04.031
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发表时间：
2018-07
期刊：
影响因子：
14
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Li L;Hu S;Chen X
近年来，CRISPR(簇状规则间隔短回文重复序列)/CAS(CRISPR相关)基因组编辑系统已成为基础生物医学研究和治疗应用中最强大的平台之一。到目前为止，有效地将CRISPR/Cas9系统体内递送到靶细胞仍然是一个挑战。虽然病毒载体已被广泛应用于体内和体外CRISPR/Cas9系统的转运，但其致癌风险、插入长度有限、免疫应答和难以大规模生产等基本缺点严重限制了其进一步应用。迫切需要CRISPR/CAS9的替代非病毒递送系统。随着非病毒载体的快速发展，基于脂质或聚合物的纳米载体在CRISPR/Cas9传递方面显示出巨大的潜力。在这篇综述中，我们分析了以质粒、mRNA或蛋白质的形式传递CRISPR/Cas9系统的利弊，并讨论了基于CRISPR/Cas9的基因组编辑的局限性和挑战。此外，还对目前已用于CRISPR/Cas9体外和体内递送的非病毒载体进行了详细的概述。最后，强调了CRISPR/CAS9系统非病毒传递的主要障碍，并提出了克服这些障碍的有希望的策略。
In recent years, CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) genome editing systems have become one of the most robust platforms in basic biomedical research and therapeutic applications. To date, efficient in vivo delivery of the CRISPR/Cas9 system to the targeted cells remains a challenge. Although viral vectors have been widely used in the delivery of the CRISPR/Cas9 system in vitro and in vivo, their fundamental shortcomings, such as the risk of carcinogenesis, limited insertion size, immune responses and difficulty in large-scale production, severely limit their further applications. Alternative non-viral delivery systems for CRISPR/Cas9 are urgently needed. With the rapid development of non-viral vectors, lipid- or polymer-based nanocarriers have shown great potential for CRISPR/Cas9 delivery. In this review, we analyze the pros and cons of delivering CRISPR/Cas9 systems in the form of plasmid, mRNA, or protein and then discuss the limitations and challenges of CRISPR/Cas9-based genome editing. Furthermore, current non-viral vectors that have been applied for CRISPR/Cas9 delivery in vitro and in vivo are outlined in details. Finally, critical obstacles for non-viral delivery of CRISPR/Cas9 system are highlighted and promising strategies to overcome these barriers are proposed.
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影响因子：
46.9
作者：
Bikard, David;Euler, Chad W.;Jiang, Wenyan;Nussenzweig, Philip M.;Goldberg, Gregory W.;Duportet, Xavier;Fischetti, Vincent A.;Marraffini, Luciano A.
通讯作者：
Marraffini, Luciano A.
影响因子：
16.6
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影响因子：
5.1
作者：
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9.7
作者：
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通讯作者：
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影响因子：
15
作者：
Alsaiari, Shahad K.;Patil, Sachin;Khashab, Niveen M.
通讯作者：
Khashab, Niveen M.