Transport of Molecular Cargo by Interaction with Virus-Like Particle RNA.
Transport of Molecular Cargo by Interaction with Virus-Like Particle RNA.
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DOI：
10.1002/anie.202111687
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发表时间：
2022-01-10
影响因子：
16.6
通讯作者：
Finn, M. G.
中科院分区：
文献类型：
--
作者：
Das, Soumen;Yau, Mei-Kwan;Noble, Jeffery;De Pascalis, Lucrezia;Finn, M. G.
来源于光滑病毒科病毒粒子的病毒样颗粒（VLP）含有大量的细胞和质粒来源的RNA。该多核苷酸作为有效结合嵌入染料噻唑橙子（TO）的储库。将用TO末端官能化的不同长度的聚乙二醇（PEG）分子和寡肽装载到VLP中，直至衣壳蛋白质质量的约50%（每个颗粒数百至数千个货物分子，取决于大小）。TO-PEG结合的动力学包括长链通过衣壳孔爬行的显著熵成本。在大多数情况下，货物分子在20-120小时内按照简单的可逆一级动力学释放。这些观察结果定义了一个简单的一般方法的非共价包装，并随后释放，核蛋白纳米笼内的功能分子的方式独立于修改的衣壳蛋白。把他们接回来再送回去。嵌入染料如噻唑橙子（TO）与多核苷酸的结合允许用分子货物装载富含RNA的病毒样颗粒，然后通过扩散释放该货物的简单方法。由于壳内的RNA浓度很高，TO标记的分子出来的速度比进去的速度慢得多;令人惊讶的是这些容易生产的纳米容器可以携带多少货物。
Virus-like particles (VLPs) derived from Leviviridae virions contain substantial amounts of cellular and plasmid-derived RNA. This encapsidated polynucleotide serves as a reservoir for the efficient binding of the intercalating dye thiazole orange (TO). Polyethylene glycol (PEG) molecules and oligopeptides of varying length, end-functionalized with TO, were loaded into VLPs up to approximately 50% of the mass of the capsid protein (hundreds to thousands of cargo molecules per particle, depending on size). The kinetics of TO-PEG binding included a significant entropic cost for the reptation of long chains through the capsid pores. Cargo molecules were released over periods of 20–120 hours following simple reversible first-order kinetics in most cases. These observations define a simple general method for the noncovalent packaging, and subsequent release, of functional molecules inside nucleoprotein nanocages in a manner independent of modifications to the capsid protein. Pick ‘em up and drop ‘em off. The binding of intercalating dyes such as thiazole orange (TO) to polynucleotides allows for a simple method to load RNA-rich virus-like particles with molecular cargo, and then to release that cargo by diffusion. TO-labeled molecules come out much slower than they go in because of the high RNA concentration inside the shell; the surprise is how much cargo these easily-produced nanocontainers can carry.
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