分会

第三十二分会：化学生物学

摘要

Chronic hepatitis B (CHB) remains a global health concern since new cases of CHB will rise to three million per year by 2030 without novel treatment strategies. Now, nucleic acid therapies have been regarded as the most prospective strategies for curing CHB. There are many siRNA or antisense oligonucleotide (ASO) drugs now on clinical trials and can successfully reduce the level of HBsAg during the treatment. Single-stranded small interfering RNAs (ss-siRNAs) are useful tools that may combine the RNAi mechanism and ASO approach. Also, as the ss-siRNA cannot be phosphorylated in the cytoplasm, 5ʹ-phosphate is crucial for activating Ago2. ss-siRNAs without 5ʹ-phosphate lose their gene silencing activities even with fully 2ʹ-F or 2ʹ-OMe modification. However, in our research, with the delivery system composed of a neutral cytidinyl lipid DNCA, and a cationic lipid CLD, the ss-siRNAs can successfully inhibit both X gene mRNA expression and HBeAg level of HBV infected HepG2 cells. And the ss-siRNA contains fully chemical modification at 2ʹ of nucleosides and essential phosphorothioate, while free from 5ʹ-phosphate. This inhibition may due to a combination of RNAi and RNase H activating, and the exact mechanism needs further demonstration.

关键词

ss-siRNA;modification;chronic hepatitis B;DNCA;CLD

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