Poster abstracts
Poster number 12 submitted by Shivam Chaubey
Synthetic peptide carriers enable siRNA delivery to hepatocytes
Shivam Chaubey (The ohio state university), Dennis Bong (Department of Chemistry and Biochemistry)
Abstract:
Small interfering RNA (siRNA) is one of several ways nucleic acid therapeutics affect gene silencing . In recent years, the U.S. Food and Drug Administration (FDA) has approved several siRNA-based therapeutics; however, there are still significant challenges; one of the most critical hurdles is effective delivery to the cytosol. 1 Various delivery systems have been developed to overcome these challenges. The prevailing method for siRNA delivery includes LNP, viral vectors, aptamers, and cell-penetrating peptides. siRNA delivery and gene silencing by RNAi have gained much importance recently, and the need for enhanced siRNA delivery platforms has propelled investigations to the forefront. Herein, we report on a novel method for delivering siRNAs based on a novel hybridization strategy. Our preliminary studies target the expression of ApoB, the major protein component of low-density lipoprotein (LDL) produced in liver and hepatocyte-derived cells. 2 In this work, we applied the synthetic hybridization approach to siRNA targeting ApoB in a hepatocyte-derived cell line (HepG2). We found that siRNA carrier binding was sufficient to enable functional silencing delivery of uridylate-modified siRNA to HepG2 cells in culture with comparable performance to lipofectamine. Preliminary knockdown studies (RT-qPCR)show low nanomolar IC 50 silencing of the endogenous ApoB gene. Notably, this new synthetic carrier affords a striking improvement in siRNA transport into mammalian cell culture without covalent RNA modification or lipid particle formation. Overall, our initial results could lead to a new siRNA delivery platform with unique advantages for siRNA therapeutics.
Keywords: siRNA, siRNA delivery, bPNA