Comparison of L, D-isomers of Rvg-9R peptides for efficient siRNA delivery

Abstract

Rvg-9R is a non-viral vector that specifically delivers siRNA to the acetylcholine receptor expressed cells. 9R residues of Rvg-9R are used as a carrier. The d-isomer of nona-arginine is added to the c-terminal end of Rvg peptides that delivers siRNA to the acetylcholine receptor expressed Neuronal cells. Rvg-9R peptide was able to bind and deliver siRNA to neuronal cells in vitro, resulting in efficient gene silencing. And this peptide showed transvascular delivery of siRNA to the brain, resulting in specific gene silencing. However, l-isomer of Rvg-9R peptide has not been yet tested to deliver siRNA. d and l-isomer of Rvg-9R/siRNA complexes were characterized as a nanoparticle and compared for which is more efficient for siRNA delivery and target gene silencing. Results showed that d-isomer of Rvg-9R were little more efficient for siRNA delivery and gene silencing effects. These results seem to occur because the d-isomer of the peptide does not degrade in the lysosome and has a better chance to escape from endosomes. It was proved that chloroquine treatment increased two types of Rvg-9R/siRNA silencing effects. However, there were no significant differences in the nanoparticle characters, siRNA delivery efficiency and gene silencing effects. Because of the poor siRNA knockdown made the results unclear. Futher studies will be needed with improved siRNA knockdown to display clearer gene silencing effects.