Artificial cationic peptides that increase nuclease resistance of siRNA without disturbing RNAi activity

Abstract

Properties of cationic peptides bearing amino or guanidino groups with various side chain lengths that bind to double stranded RNAs (dsRNAs) were investigated. Peptides with shorter side chain lengths effectively bound to dsRNAs (12mers) increasing their thermal stability. NMR measurements suggested that the cationic peptide binds to the inner side of the major groove of dsRNA. These peptides also increased the thermal stability of siRNA and effectively protected from RNase A digestion. On the other hand, both peptides containing amino groups and guanidine groups did not disturb RNAi activity.

Keywords:

• RNA binding peptides
• cationic peptides
• artificial peptides
• RNAi drug
• DDS

Acknowledgments

We thank Mr. Taku Suenaga (Tokyo University of Science) for technical support to some experiments.

Additional information

Funding

This study was supported by grants from Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Japan (Molecular Technology).