posted on 2024-02-05, 13:35authored byChandan Pal, Michael Richter, Eriks Rozners
Chemical
modifications of RNA are important tools for the development
of RNA therapeutics. The present study reports a novel RNA backbone
modification that replaces the negatively charged phosphate with a
positively charged amine linkage. Despite being thermally destabilizing
in RNA duplexes, the amine linkage caused a relatively modest decrease
of activity of a modified short interfering RNA (siRNA). At position
2 of the guide strand, the amine modification strongly enhanced the
specificity of siRNA while causing an ∼5-fold drop of on-target
activity. These results support the future development of amines as
cationic RNA modifications and novel tools to modulate protein–RNA
interactions.