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[Study on anti-HBV effects by antisense oligodeoxynucleotides in vitro]
1Department of Microbiology and Immunology, Shandong University, Ji'nan 250012, China.
Objective:
To study the inhibition effect of anti-HIV oligodeoxy-nucleotides on HBV X gene.
Methods:
Three antisense phosphorothioate oligodeoxy-nucleotides(AsON) complementary to the initiator of X, DR2, EN II respectively, were synthesized and tested for their anti-HBV activity on HepG2.2.15 cells with ELISA methods.
Results:
When the best effect concentration of AsON was 10 mumol/L, the inhibition rates on HBsAg of three AsON were 57%, 60% and 52% respectively, and on HBeAg were 56%, 45% and 56% respectively. There were two inhibition peaks at different times. There was no inhibition effect treated by random control (< 12%). Using the 3-(4,5-dimethythiazol-xyl)-2,5-diphnyl tetrazolium bromide method, there was no cytotoxicity at 40 mumol/L of AsON.
Conclusion:
AsONs on three key region of X gene were effective drugs to inhibit the expression of HBV.
Insights
Antisense oligodeoxynucleotides (AsONs) effectively inhibited Hepatitis B virus (HBV) X gene expression. These novel anti-HBV drugs showed significant inhibition rates without cytotoxicity, offering a promising therapeutic avenue.
Area of Science:
- Molecular Biology
- Virology
- Antiviral Drug Development
Background:
- Hepatitis B virus (HBV) X gene plays a crucial role in viral replication and pathogenesis.
- Developing effective antiviral strategies targeting specific HBV genes is essential.
Purpose of the Study:
- To investigate the inhibitory effects of anti-HIV oligodeoxynucleotides (AsONs) on the HBV X gene.
- To evaluate the potential of AsONs as therapeutic agents against HBV infection.
Main Methods:
- Synthesis of three antisense phosphorothioate oligodeoxy-nucleotides (AsONs) complementary to key regions of the HBV X gene.
- Assessment of anti-HBV activity in HepG2.2.15 cells using ELISA and MTT assays.
- Determination of inhibition rates for HBsAg and HBeAg, and evaluation of cytotoxicity.
Main Results:
- The synthesized AsONs demonstrated significant inhibition of HBsAg (52-60%) and HBeAg (45-56%) expression at a concentration of 10 μmol/L.
- Two distinct inhibition peaks were observed over time, indicating sustained antiviral activity.
- No significant inhibition was observed with a random control ( < 12%), and no cytotoxicity was detected at 40 μmol/L of AsON.
Conclusions:
- Antisense oligodeoxynucleotides targeting three key regions of the HBV X gene are effective in inhibiting HBV gene expression.
- These AsONs represent promising therapeutic candidates for the treatment of HBV infection due to their efficacy and safety profile.