分會(huì)

第三十二分會(huì)：化學(xué)生物學(xué)

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, 5?-phosphate is crucial for activating Ago2. ss-siRNAs without 5?-phosphate lose their gene silencing activities even with fully 2?-F or 2?-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 2? of nucleosides and essential phosphorothioate, while free from 5?-phosphate. This inhibition may due to a combination of RNAi and RNase H activating, and the exact mechanism needs further demonstration.

關(guān)鍵詞

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

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