Cell-penetrating peptides for efficient siRNA transport

Abstract

Arginine-rich peptides such as TAT or poly-9-D-Arg (9dR) have been used as cell penetrating peptide (CPP) for intracellular delivery of nucleic acids. Recently, we have used the 9dR as a siRNA carrier conjugated to target moiety. However, low efficiency of 9dR conjugation to target moiety need to be improved. Thus, we made a 9-L-Arg (9lR) as a fusion protein with targeting proteins/peptide and test efficiency of siRNA. Despite 100% conjugation of 9lR to target moiety, equal amount of siRNA has been complexed with D-9R or L-9R indicating 9dR complex with siRNA. Interestingly, efficiency of target gene silencing was better in cells treated with 9dR by 30%. These results indicate that D-arginine is better in complex with siRNA than L-Argine. Mechanism has to be elucidated.