Improving the potency prediction for chemically modified siRNAs through insights from molecular modeling of individual sequence positions.

ABSTRACT: Chemical modifications are applied to small interfering RNAs (siRNAs) to improve their metabolic stability, specificity, and duration of pharmacodynamic effects. Despite tremendous progress made, identifying chemically modified siRNAs with drug-like properties requires empirical screening due to an intricate interdependence of siRNA sequence and chemistry, i.e., the nature and position of chemical modifications within the siRNA duplex. To improve our ability to design fully modified, potent siRNAs, we combined experimental measurements of thermodynamic stability and biological activity in vitro with extensive molecular modeling in silico of the structural, dynamic, and energetic properties of parent (unmodified) siRNA duplex sequences compared with their chemically modified v

SUBMITTER: Kliuchnikov E 

PROVIDER: S-EPMC11960531 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature