Exploring PAZ/3'-overhang interaction to improve siRNA specificity. A combined experimental and modeling study.

ABSTRACT: The understanding of the dynamical and mechanistic aspects that lie behind siRNA-based gene regulation is a requisite to boost the performance of siRNA therapeutics. A systematic experimental and computational study on the 3'-overhang structural requirements for the design of more specific and potent siRNA molecules was carried out using nucleotide analogues differing in structural parameters, such as sugar constraint, lack of nucleobase, distance between the phosphodiester backbone and nucleobase, enantioselectivity, and steric hindrance. The results established a set of rules governing the siRNA-mediated silencing, indicating that the thermodynamic stability of the 5'-end is a crucial determinant for antisense-mediated silencing but is not sufficient to avoid sense-mediated silencing. Bo

SUBMITTER: Alagia A 

PROVIDER: S-EPMC5896489 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature