Design and systematic evaluation of novel chemical modification patterns enable the identification of a potent siRNA targeting <i>PCSK9</i>.

ABSTRACT: Fully modified small interfering RNAs (siRNAs) have demonstrated remarkable advantages in medicine development since they enable the knockdown of the majority of disease-related proteins. However, unmodified siRNAs usually cannot be used for medications due to their biochemical instability. siRNA modification patterns are engineered to enhance both structural stability and pharmacodynamic efficacy, thus being vital in the development of potent siRNA drugs. However, most modification patterns of approved or clinically investigated siRNAs are protected by patents, significantly restricting their broader application. Therefore, the development of proprietary modification patterns has been essential for siRNA therapeutics companies. Here, based on a comprehensive analysis of existing studies,

SUBMITTER: Huang ZA 

PROVIDER: S-EPMC12590278 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature