Synthesis and in vitro assessment of chemically modified siRNAs targeting BCL2 that contain 2'-ribose and triazole-linked backbone modifications

Abstract

Short interfering RNAs (siRNAs) are biomolecules used for post-transcriptional gene regulation, and therefore hold promise as a future therapeutic by silencing gene expression of overexpressed deleterious genes. Chemically modifying the RNA structure is used to overcome the inherent limitations of the RNA structure. This project investigated the ability of a library of chemically modified siRNAs to target, the therapeutically relevant oncogene, BCL2, by combining 2'-ribose sugar modifications with a novel triazole-linked backbone modification. Solid support phosphoramidite chemistry was used to incorporate chemical modifications at various positions within anti-BCL2 siRNAs. In vitro effects were evaluated through qPCR, cell viability, nuclease stability, and an immunological ELISA assay.