Related Experiment Videos
[Inhibitory effect of triplex forming oligodeoxynucleotides on HBV replication and synthesis of antigen]
1Viral Hepatitis Research Unit, Third Affiliated Hospital, Sun Yat-sen University of Medical Sciences, Guangzhou.
Objective:
To explore the inhibitory effect of triplex forming oligodeoxynucleotides(TFO) on replication of HBV and synthesis of antigen.
Methods:
A 21 mer phosphorothioate triplex forming oligodeoxynucleotides (TFO21) directed at SP1 sites in HBV core promoter and a control of 21 mer phosphorothioate oligodeoxynucleotides (ODNcon) were synthesized. HepG 2.2.15 cells which can produce HBsAg, HBeAg, HBV DNA and HBV particle were treated with TFO21 and ODNcon. In HepG 2.2.15 cells treated with these oligodeoxynucleotides, the levels of HBsAg, HBeAg, and HBV DNA were examined by ELISA and dot hybridization method, respectively.
Results:
The levels of HBsAg, HBeAg and HBV DNA in TFO21 group were lower than those in the bank control group. At concentration of 10 mumol/L, TFO21 inhibited synthesis of HBsAg and HBeAg by 57.5% and 77%. The inhibitory effect of TFO21 was dosage-dependent, and was related to time in which 2.2.15 cells were incubated with TFO21. No inhibition was observed in the ODNcon group. No toxicity was observed in the 2.2.15 cells treated with oligodeoxynucleotides.
Conclusion:
These results indicate that TFO is a potent inhibitor for HBV replication and synthesis of antigen, and also suggest that TFO is a therapeutic potential for the treatment of patients infected with HBV.
Insights
Triplex forming oligodeoxynucleotides (TFO) significantly inhibit hepatitis B virus (HBV) replication and antigen synthesis. TFO demonstrates therapeutic potential for treating HBV infection without observed toxicity.
Area of Science:
- Molecular Biology
- Virology
- Oligonucleotide Therapeutics
Context:
- Hepatitis B virus (HBV) infection remains a significant global health challenge.
- Current treatments for HBV are limited, necessitating novel therapeutic strategies.
- Oligodeoxynucleotides offer a promising avenue for antiviral development.
Purpose:
- To investigate the efficacy of triplex forming oligodeoxynucleotides (TFO) in inhibiting HBV replication.
- To assess the impact of TFO on hepatitis B surface antigen (HBsAg) and hepatitis B e-antigen (HBeAg) synthesis.
- To evaluate the safety and dosage-dependent effects of TFO in HBV-producing cells.
Summary:
- A 21-mer phosphorothioate TFO (TFO21) targeting HBV core promoter SP1 sites was synthesized and tested in HepG 2.2.15 cells.
- TFO21 treatment resulted in significant reductions in HBsAg, HBeAg, and HBV DNA levels.
- Inhibition was dose- and time-dependent, with no observed toxicity, unlike a control oligodeoxynucleotide (ODNcon).
Impact:
- TFO demonstrates potent antiviral activity against HBV replication and antigen production.
- These findings suggest TFO as a potential therapeutic agent for patients with chronic HBV infection.
- The study highlights the promise of TFO-based therapies in combating viral diseases.