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Optimization in Chemical Modification of Single-Stranded siRNA Encapsulated by Neutral Cytidinyl/Cationic Lipids.

ABSTRACT: Single-stranded siRNA (ss-siRNA) refers to the antisense strand of siRNA, which plays the role of gene silencing. Since single-stranded RNA is unstable, the present study employed a homemade neutral cytidinyl/cationic lipid delivery system and chemical modifications to improve its stability. The results showed that with the aid of mixed lipids, ss-siRNA could knock down 40% of target mRNA at 25 nM. With 2'-F/2'-OMe, phosphorothioate and 5'-terminal phosphorylation, the optimized ss-siRNA could knock down 80% of target mRNA at 25 nM. Further knocking down AGO2, the ss-siRNAs could not effectively silence target mRNAs. Analysis of the biodistribution in vivo showed that ss-siRNA was less durable than siRNA, but spread more quickly to tissues. This study provides a safe and efficient ss-siRNA delivery and modification strategy, which lays the foundation for future works.

SUBMITTER: Li Z

PROVIDER: S-EPMC8957067 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Optimization in Chemical Modification of Single-Stranded siRNA Encapsulated by Neutral Cytidinyl/Cationic Lipids.

Li Zheng Z Wang Xixian X Zhou Xinyang X Wang Jie J Guan Zhu Z Yang Zhenjun Z

Frontiers in chemistry 20220307

Single-stranded siRNA (ss-siRNA) refers to the antisense strand of siRNA, which plays the role of gene silencing. Since single-stranded RNA is unstable, the present study employed a homemade neutral cytidinyl/cationic lipid delivery system and chemical modifications to improve its stability. The results showed that with the aid of mixed lipids, ss-siRNA could knock down 40% of target mRNA at 25 nM. With 2'-F/2'-OMe, phosphorothioate and 5'-terminal phosphorylation, the optimized ss-siRNA could k ...[more]

PMID: 35345539

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