The synthesis and in vitro evaluation of short interfering RNA containing triazole functionalized sphingolipid-based derivatives

Abstract

RNA Interference (RNAi) is a natural cellular process that silences the expression of a target gene in a sequence-specific manner by mediating targeted mRNA degradation. One of the main challenges in RNAi research is developing an effective delivery system for siRNAs. Recently, fatty acid conjugated siRNAs have shown promising potential as safe and effective method to deliver oligonucleotides to extrahepatic cells. A class of fatty acids that we are interested in are sphingolipids, they are a class of lipids containing a backbone of sphingoid bases and aliphatic amino alcohols. Sphingolipids show potential as lipid-conjugated siRNAs as they are important structural and functional components of plasma membranes of eukaryotic cells. Here, we design a library of siRNAs containing propyl-triazole modified sphingosine at various locations of the sense and antisense strand of the reporter gene firefly luciferase and evaluate its gene-silencing abilities in both the presence and absence of a transfection carrier.