# name
RNA major groove modifications improve siRNA stability and biological activity

# metadata.dc.description.abstract[].value
RNA 5-methyl and 5-propynyl pyrimidine analogs were substituted into short interfering RNAs (siRNAs) to probe major groove steric effects in the active RNA-induced silencing complex (RISC). Synthetic RNA guide strands containing varied combinations of propynyl and methyl substitution revealed that all C-5 substitutions increased the thermal stability of siRNA duplexes containing them. Cellular gene suppression experiments using luciferase targets in HeLa cells showed that the bulky 5-propynyl modification was detrimental to RNA interference activity, despite its stabilization of the helix. Detrimental effects of this substitution were greatest at the 5′-half of the guide strand, suggesting close steric approach of proteins in the RISC complex with that end of the siRNA/mRNA duplex. However, substitutions with the smaller 5-methyl group resulted in gene silencing activities comparable to or better than that of wild-type siRNA. The major groove modifications also increased the serum stability of siRNAs.

# metadata.dc.rights[].value
cc-by-nc (c) Terrazas Martínez, Montserrat et al., 2009

# metadata.dc.source[].value
Articles publicats en revistes (Química Inorgànica i Orgànica)

# metadata.dc.title[].value
RNA major groove modifications improve siRNA stability and biological activity