RNA干扰
RNA沉默
内吞作用
网格蛋白
纳米载体
壳聚糖
细胞生物学
小干扰RNA
核糖核酸
基因沉默
生物
化学
生物化学
基因
药物输送
受体
有机化学
作者
Hong Zhou,Fenglin Wan,Yufan Jian,Fuyou Guo,Miao Zhang,Shiyao Shi,Liang Yang,Shili Li,Ying Liu,Wei Ding
标识
DOI:10.1016/j.ijbiomac.2023.127021
摘要
Chitosan, as a promising gene nanocarrier for enhancing RNA interference (RNAi) efficiency, displays tremendous application prospects in addressing dsRNA delivery concerns. However, the molecular mechanism of chitosan/dsRNA polyplex nanoparticles (PNs) for advancing dsRNA delivery efficiency remains largely unknown. Here, chitosan/dsRNA PNs were prepared by an electrostatic attraction method. The results showed that the chitosan/dsRNA PNs significantly advance stability, and cellular uptake efficiency of dsRNA, and RNAi efficiency. RNA-Seq and qPCR assays further revealed that chitosan/dsRNA PNs upregulated the key clathrin heavy chain (CHC) gene for activating clathrin-dependent endocytosis (CDE) pathway. Additionally, inhibition of CDE hindered the robust RNAi responses of chitosan/dsRNA PNs using an inhibitor (chlorpromazine) and an RNAi-of-RNAi strategy. Ultimately, microscale thermophoresis assay confirmed that chitosan/dsRNA PNs directly bound to CHC protein, which was a core component in CDE, to advance RNAi efficiency. To our knowledge, our findings firstly illuminate the molecular mechanism how chitosan nanoparticles-based RNAi deliver dsRNA for enhancing RNAi efficiency. Above mechanism will advance the extensive utilization of nanocarrier-based RNAi in pest management and gene delivery.
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