Department of Chemistry and Biochemistry, California State University Long Beach, 1250 Bellflower Blvd, Long Beach, California, 90840, USA.
Department of Biological Sciences, California State University Long Beach, 1250 Bellflower Blvd, Long Beach, California, 90840, USA.
Sci Rep. 2019 Nov 14;9(1):16875. doi: 10.1038/s41598-019-53462-1.
The higher-order architecture observed in biological systems, like viruses, is very effective in nucleic acid transport. The replications of this system has been attempted with both synthetic and naturally occurring polymers with mixed results. Here we describe a peptide/siRNA quaternary complex that functions as an siRNA delivery system. The rational design of a peptide assembly is inspired by the viral capsids, but not derived from them. We selected the collagen peptide (COL) to provide the structural stability and the folding framework, and hybridize it with the cell penetrating peptide (CPP) that allows for effective penetration of biological barriers. The peptide/siRNA quaternary complex forms stoichiometric, 10 nm nanoparticles, that show fast cellular uptake (<30 min), effective siRNA release, and gene silencing. The complex provides capsid-like protection for siRNA against nucleases without being immunostimulatory, or cytotoxic. Our data suggests that delivery vehicles based on synthetic quaternary structures that exhibit higher-order architecture may be effective in improving delivery and release of nucleic acid cargo.
在病毒等生物系统中观察到的高级结构在核酸运输中非常有效。已经尝试使用合成和天然存在的聚合物来复制该系统，但结果喜忧参半。在这里，我们描述了一种肽/siRNA 四元复合物，它可作为 siRNA 递药系统。肽组装的合理设计受病毒衣壳的启发，但并非源自它们。我们选择胶原肽 (COL) 提供结构稳定性和折叠框架，并将其与允许有效穿透生物屏障的穿透肽 (CPP) 杂交。该肽/siRNA 四元复合物形成化学计量的、10nm 纳米颗粒，表现出快速的细胞摄取（<30min）、有效的 siRNA 释放和基因沉默。该复合物为 siRNA 提供类似衣壳的保护，防止核酶降解，同时不具有免疫刺激性或细胞毒性。我们的数据表明，基于表现出高级结构的合成四元结构的递药载体可能有效提高核酸货物的递药和释放。
