Dextran-Conjugated Caged siRNA Nanoparticles for Photochemical Regulation of RNAi-Induced Gene Silencing in Cells and Mice
Dextran-Conjugated Caged siRNA Nanoparticles for Photochemical Regulation of RNAi-Induced Gene Silencing in Cells and Mice
复制标题
葡聚糖缀合的笼状 siRNA 纳米颗粒用于光化学调节细胞和小鼠中 RNAi 诱导的基因沉默
DOI：
10.1021/acs.bioconjchem.9b00204
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发表时间：
2019-05-01
影响因子：
4.7
通讯作者：
Tang, Xinjing
中科院分区：
文献类型：
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作者：
Chen, Changmai;Wang, Zhongyu;Tang, Xinjing
基于RNA干扰（RNAi）的基因治疗是一种在体内或体外高效序列特异性基因沉默的精确治疗方法。利用光不稳定性连接子将反义和正义RNA链通过葡聚糖偶联形成笼状RNA，并通过自组装形成笼状siRNA纳米颗粒（Dex-p-siRNA），用于靶基因表达的光调控。由于葡聚糖-siRNA纳米颗粒的形成，葡聚糖缀合的笼状siRNA纳米颗粒显示出显著的血清核酸酶抗性。使用制备的笼状Dex-p-siRNA纳米颗粒实现了细胞中外源GFP和内源性有丝分裂驱动蛋白-5（Eg 5）基因表达的光调节。靶向GFP的笼状Dex-p-siRNA纳米颗粒通过瘤内注射成功地光调节了荷瘤小鼠中的GFP表达。具有高血清稳定性的笼状siRNA纳米颗粒不仅在体外和体内应用中显示出对外源和内源基因表达的光调控的巨大前景，而且还提供了时空控制RNAi诱导的基因沉默的新颖且方便的方法。
RNA interference (RNAi)-based gene therapy is a precision therapeutic approach for highly efficient sequence-specific gene silencing in vivo or in vitro. Caged RNAs featuring dextran conjugation of antisense and sense RNA strands using photolabile linker were rationally designed and self-assembled to form caged siRNA nanoparticles (Dex-p-siRNA) for photoregulation of target gene expression. The dextran-conjugated caged siRNA nanoparticles showed significant serum nuclease-resistance due to the formation of dextran-siRNA nanoparticles. Photomodulation of exogenous GFP and endogenous mitotic kinesin-5 (Eg5) gene expression in cells was achieved using the prepared caged Dex-p-siRNA nanoparticles. The caged Dex-p-siRNA nanoparticles targeting GFP successfully photoregulated GFP expression in tumor-bearing mice via intratumoral injection. Caged siRNA nanoparticles with high serum stability not only show great promise for photoregulation of exogenous and endogenous gene expression for both in vitro and in vivo applications, but also provide a novel and convenient way to spatiotemporally control RNAi-induced gene silencing.