反义寡脱氧核苷酸对HBsAg、HBeAg表达的影响

Inhibition of HBsAg and HBeAg Expression by ASODN of Various Regions of the HBV Genome

目的探讨硫代磷酸反义寡脱氧核苷酸对乙型肝炎病毒H BsAg、H BeAg的影响。方法应用ELISA方法检测培养H ep G22215细胞的H BsAg、H BeAg的表达。设计合成H BV5个硫代反义寡聚核苷酸(S-asODN)靶序列,观察不同靶序列及联合使用对H BV基因复制和表达的影响。结果本细胞株表达H BsAg、H BeAg的S/C.D均>5,不同靶位点的S-as ODN对H BsAg、H BeAg表达都有显著的抑制作用及序列特异性,联合用药后对H BsAg和H BeAg的抑制效果有显著的提高。结论S-as ODN对H ep G22215的H BsAg、H BeAg具有一定的抑制作用,表现为序列特异性、剂量相关性、联合协同性。

Objective To study the effect of antisense phosphorothioate oligodeoxynucleotides （S-as ODN） of various regions of the HBV genome on the expression of HBsAg and HBeAg in the HepG22215 cell line. Method The expression levels of HBsAg and HBeAg in the HepG22215 cell line were determined by ELISA. According to gene structure of HBV, 5 S-as ODNs were designed and synthesized. The effect of different ASODNs on the expression of HBsAg and HBeAg was analyzed. Results This confirmed the characteristics of HepG22215 which could produce HBsAg and HBeAg. All 5 S-as ODNs could specifically inhibit the production of HBsAg and HBeAg in HepG22215 cells. A combination of drug and ASODN could enhance the inhibition. Conclusion These results suggest that S-as ODN may be a potential new therapy for anti-HBV. The inhibition showed sequence-specific, dose-dependent and drugcooperative effects.