Characterization and Evaluation of Hybrid Collagen/Cell Penetrating Peptides for SiRNA Deliver

Short interfering RNA (siRNA) causes sequence specific gene silencing of mRNA and has been shown to be a very promising therapeutic agent for a wide range of diseases. We have developed a hybrid collagen/cell penetrating peptide (CHP), that contains a triple helical domain (POG)n that provides stability, and a cell penetrating domain (Rn) which contains positively charged arginine residues allowing for internalization into cells. We determined that the CHPs form highly crystalline nanoparticles with siRNA with molar ratios of 1:18 and 1:9 depending on the number of arginines in the CPP domain. CHPs are able to effectively deliver and release siRNA into 3T3 Swiss mouse fibroblast cells with higher efficiency and gene silencing ability than that of Lipofectamine. The data suggest that our strategy for development of the CHP-siRNA complex can provide an avenue for effective delivery of siRNA.