RNA interference (RNAi), a cellular mechanism for regulating gene expression found in nearly all organisms, can be exploited for research and medical purposes. Synthetic double-stranded RNA molecules called short interfering RNAs (siRNAs) are used in such applications to silence gene expression, but the therapeutic potential of siRNAs is limited because the molecules are not “drug-like.”

Martin Egli and colleagues are investigating how chemical modifications affect the efficacy of siRNAs. In papers published recently in Angewandte Chemie and Nucleic Acids Research, they report on the promising properties of siRNAs modified with fluorine (2′-F siRNAs).

They show that 2′-F siRNAs are more stable and more effective at silencing genes than an unmodified siRNA. In experiments with human white blood cells, the 2′-F-modified siRNA did not stimulate a significant immune response. Using crystal structures of the modified molecules, the researchers also evaluated the biophysical properties of the molecules. The findings suggest that fluorine modification may improve the efficacy of siRNAs for research and medical uses.