Peptide Self-assembly into stable Capsid-Like nanospheres and Co- assembly with DNA to produce smart artificial viruses
Peptide Self-assembly into stable Capsid-Like nanospheres and Co- assembly with DNA to produce smart artificial viruses
复制标题
肽自组装成稳定的衣壳样纳米球并与DNA共组装产生智能人工病毒
DOI：
10.1016/j.jcis.2022.01.181
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发表时间：
2022-02-09
影响因子：
9.9
通讯作者：
Wang, Ming
中科院分区：
文献类型：
--
作者：
Cao, Meiwen;Zhang, Zijin;Wang, Ming
通过重新设计的多肽与DNA的共组装，已经成功地开发了智能人工病毒，实现了对肿瘤细胞的刺激响应性和高效的基因转染。这些肽被设计为包含几个功能片段，包括驱动自组装的疏水芳族片段，通过形成二硫键来调节组装形状并稳定组装的纳米结构的两个或更多个半胱氨酸，促进与DNA共组装并结合到细胞膜的几个赖氨酸，以及引入癌症敏感性的酶可切割片段。合理设计的肽自组装成直径小于10 nm的稳定纳米球，其作为captase样亚基进一步与DNA相互作用，通过将DNA封装在内部产生分层病毒模拟结构。这种人工病毒可以有效地保护DNA免受核酸酶消化，并通过酶触发的结构拆卸实现高效的基因组释放，从而确保肿瘤细胞中的高水平基因转染。该系统从衣壳形成、基因组包装和基因转染等方面较好地模拟了天然病毒的结构和功能特性，有望作为高效基因载体应用。(c)2022爱思唯尔公司All rights reserved.
Smart artificial viruses have been successfully developed by co-assembly of de novo designed peptides with DNA, which achieved stimuli-responsibility and efficient gene transfection in cancer cells. The peptides were designed to incorporate several functional segments, including a hydrophobic aromatic segment to drive self-assembly, two or more cysteines to regulate the assemblage shape and stabilize the assembled nanostructures via forming disulfide bonds, several lysines to facilitate co-assembly with DNA and binding to cell membranes, and an enzyme-cleavable segment to introduce cancer sensitivity. The rationally designed peptides self-assembled into stable nanospheres with a uniform diameter of < 10 nm, which worked as capsid-like subunits to further interact with DNA to produce hierarchical virus-mimicking structures by encapsulating DNA in the interior. Such artificial viruses can effectively protect DNA from nuclease digestion and achieve efficient genome release by enzyme-triggered structure disassembly, which ensured a high level of gene transfection in tumor cells. The system emulates very well the structural and functional properties of natural viruses from the aspects of capsid formation, genome package and gene transfection, which is highly promising for application as efficient gene vectors.(c) 2022 Elsevier Inc. All rights reserved.