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BB-HB-331 is an investigational DNA-directed RNA interference (ddRNAi) gene therapy developed by Benitec Biopharma for the treatment of chronic hepatitis B virus (HBV) infection. The therapeutic consists of an adeno-associated virus serotype 8 (AAV8) vector containing a recombinant DNA expression cassette. This cassette is designed to express three distinct short hairpin RNAs (shRNAs) that target highly conserved sequences within the HBV genome, specifically those encoding the Core, S-antigen, and X-proteins. By simultaneously silencing these three viral targets, BB-HB-331 aims to achieve durable suppression of viral replication and antigen production. While preclinical studies showed promising results, including robust suppression of HBV in vivo following a single administration, the program is no longer active in Benitec's clinical development pipeline and is considered a historical program.
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