Systematic analysis of siRNA and mRNA features impacting fully chemically modified siRNA efficacy.

ABSTRACT: Chemically modified small interfering RNAs (siRNAs) are a promising drug class that silences disease-causing genes via mRNA degradation. Both siRNA-specific features (e.g. sequence, modification pattern, and structure) and target mRNA-specific factors contribute to observed efficacy. Systematically defining the relative contributions of siRNA sequence, structure, and modification pattern versus the native context of the target mRNA is necessary to inform design considerations and facilitate the widespread application of this therapeutic platform. To address this, we synthesized a panel of ∼1260 differentially modified siRNAs and evaluated their silencing efficiency against therapeutically relevant mRNAs (APP, BACE1, MAPT, and SNCA) using both reporter-based and native expression assays. Ou

SUBMITTER: Davis SM 

PROVIDER: S-EPMC12205987 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature