NIAID SBIR PHS 2020-1 TOPIC 084: ANTIVIRAL DRUGS TO CURE CHRONIC HEPATITIS B VIRUS INFECTION

Hepatis B Virus (HBV) is a complex virus for which no curative drug regimen exists, representing a clinical unmet need. MicroRNA are small non-coding RNA regulating cellular pathways and are manipulated by many viruses, including HBV, for intracellular viral survival, replication and immune evasion. Recent reports and a phenotypic screen conducted by Regulus Therapeutics identified multiple microRNA targets that disrupt HBV replication. Thus, the main hypothesis of this project is that modulating HBV-associated microRNA may lead to a clinically relevant “functional cure”. The goal of this proposal is to build on these promising results by identifying novel microRNAs that are essential for HBV pathogenicity and to develop clinical candidate oligonucliotides able to target them. For that purpose, clinically relevant in vitro assays will be devloped and optimized in order to evaluate microRNA modulation (Specific Aim #1). Then, a series of unique microRNA modulators will be synthesized and optimized to allow selection of three stable and potent anti-HBV candidates (Specific Aim #2). Finally, a comprehensive funnel of bioinformatic and genomic assessments will be utilized along with the developed assays to asses the novel microRNA targets for clinical merit (Specific Aim #3).