Strategic modification of oligonucleotides with carboxylic acids containing small molecules

Abstract

Small interfering RNA (siRNA) are double-stranded RNA molecules used to manipulate gene regulation, by silencing gene expression. SiRNA molecules have been integrated into the therapeutic field, with several FDA-approved medications targeting liver-specific diseases. While effective, these therapeutics have challenges, such as increasing costs, off-target effects, and delivery systems to other organs. To combat these issues, new formulation strategies must be implemented. One method is to discover new cost-efficient delivery systems that help guide the RNA to target cells increasing the specificity and stability of the RNA. Carboxylic acids such as folic and retinoic acid have been used extensively in RNA disease and cancer research due to their strong binding affinities to folate and retinoic acid receptors in the body. This has allowed us to tag various carboxylic acids containing small molecules onto RNA using a novel, and cost-efficient chemistry protocols to investigate unique delivery systems to further increase the silencing and stability capabilities in HeLa cells.