Dextran-Conjugated Caged siRNA Nanoparticles for Photochemical Regulation of RNAi-Induced Gene Silencing in Cells and Mice
- 1 State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences , Peking University , Beijing , 100191 , China.
- 2 Medical and Health Analytical Center , Peking University , Beijing , 100191 , China.
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.