RENIGUARD LIFE SCIENCES, INC. — Department of Health and Human Services SBIR Phase I: DESCRIPTION (provided by applicant): Chronic infection by hepatitis B virus (HBV) can resu

Description

DESCRIPTION (provided by applicant): Chronic infection by hepatitis B virus (HBV) can result in cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC) if left untreated. The extent of liver injuries and the risk of HCC are positively related to thelevel of viral replication measured by serum viral load. Five oral antiviral therapies are now available to inhibit viral replication. Their effective use requires proper monitoring of drug-resistant mutant viruses. Current commercially available methodshave demonstrated the utility of this monitoring but are significantly limited by their low sensitivity and inability to quantify mutant viral load. The overall goal of this project is to develop superior assays to improve the monitoring and be able to predict drug resistance prior to treatment or shortly after the treatment is initiated. We have developed a marketable clamped DNA sequencing assay that is gt100 times more sensitive than the existing commercially available techniques. The specific objectiveof this phase I proposal is to determine the feasibility and usefulness of our new assay in mutant detection, using clinical samples and making comparisons with the current standard in the field. We have also developed a clamped quantitative PCR assay witha similar high level of sensitivity. Our secondary objective is to use this quantitative assay to demonstrate the feasibility of predicting the emergence of viral mutants prior to treatment when the treatment decisions can be beneficially affected. The assay will also allow monitoring the dynamics of mutant viruses, which may help decision making on when to start a rescue treatment. Thus this study offers innovations that can be of enormous significance in the clinical management of chronic hepatitis B.PUBLIC HEALTH RELEVANCE: Hepatitis B virus (HBV) drug-resistant mutations are major obstacles to the oral antiviral treatment. We have developed new assay platforms that are technically superior to the current commercially available methods. These assays will enhance early detection of drug resistance and aid clinical decision making.