Intracellular inhibition of the replication of hepatitis B virus by hammerhead ribozymes.

Abstract

BACKGROUND:

Chronic hepatitis B virus (HBV) infection is frequently associated with cirrhosis and hepatocellular carcinoma, and so has become a major worldwide health problem. Hammerhead ribozymes have recently gained some attention as potential tools to inhibit viral infection, for which there are no general effective therapies available.

METHODS:

A hammerhead ribozyme, RzC, was designed to target the sequence encoding the tail region of the HBV core protein. The activities of the ribozyme were analyzed in vitro and in human hepatoma (HepG2) cells.

RESULTS:

In vitro, RzC cleaves HBV-RNA at its target site up to 30%, while the disabled ribozyme, dRzC, which has a one-base mutation in the catalytic site, did not cleave the target RNA at all. When the ribozymes were cotransfected into HepG2 cells with the HBV genome-containing plasmid, p3.6II, the inhibition of HBV replication by RzC was greater than that by dRzC, indicating that the active catalytic domain of the hammerhead ribozyme could increase the extent of antisense-mediated inhibition. In addition, there was a gradient of effectiveness in which the greater the amount of released ribozyme, the greater the reduction in HBV progeny DNA.

CONCLUSIONS:

These results suggest the possibility of hammerhead ribozyme-mediated gene therapy for the treatment of HBV infections.

• Authors: Y Feng, Y Y Kong, Y Wang, G R Qi
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 16 Issue 10 Pg. 1125-30 (Oct 2001) ISSN: 0815-9319 [Print] Australia
• PMID: 11686839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• RNA, Catalytic
• hammerhead ribozyme

Topics

• Antiviral Agents (metabolism, pharmacology)
• Blotting, Southern
• Dose-Response Relationship, Drug
• Drug Design
• Enzyme-Linked Immunosorbent Assay
• Hepatitis B virus (drug effects, genetics)
• Humans
• Liver Neoplasms (pathology)
• RNA, Catalytic (genetics, metabolism, pharmacology)
• Transfection
• Tumor Cells, Cultured
• Virus Replication (drug effects)