Quaternized starch-based carrier for RNAi delivery applications

RNA interference (RNAi) therapy has emerged as a promising therapy platform however, there is an ongoing need for a safe and effective delivery carrier. Here we have developed and characterized a delivery platform based on the natural polysaccharide starch in an attempt to address unresolved delivery challenges of RNAi. Modified potato starch was successfully obtained by substitution with quaternary reagent, providing starch with cationic properties (Q-starch). The results indicate that Q-starch was able to bind RNAi by self-assembly formation of nano-complexes. For efficient and potent silencing, we monitored the physical characteristics and cellular path of the formed nano-complexes at increasing carrier to RNA (N/P) molar ratios and concentrations. Two therapeutic applications would be presented: (1) The systemic in vivo delivery of small interfering RNA (siRNA) to effectively target cancer in a murine model [1], and (2) A topical administration of micro-RNA 197 (miR-197) resulting in decreased expression of its target proteins, and a significant reduction in the psoriatic activity markers in vivo [2]. Our results demonstrate the therapeutic potential of the Q-starch carrier.

References:

1. Amar-Lewis, E., Buaron, N., Chintacunta, R., Benafsha, C., Goldbart, R., Traitel, T., Prasad, M., Elkabets, M., and Kost, J. Quaternized Starch-Based Composite Nanoparticles for siRNA Delivery to Tumors, ACS Appl. Nano Mater, 4, 2218-2229, 2021

2. Lifshiz-Zimon, R., Lerman, G., Elharrar, E., Meningher,T., Barzilai, A., Masalha, M., Chintakunta, R., Holander,E., Goldbart,R., Traitel, T., Haras, M., Sidi, Y., Avni, D., and Kost, J. Ultrasound Targeting of Q-starch/miR-197 Complexes for Topical Treatment of Psoriasis, Journal of Controlled Release, 284, 103-111, 2018