Combinatorial knock-down/knock-out strategies to reconstitute anti-viral immunity and eliminate persisting hepatitis B virus cccDNA (18)

• Subject Area: Virology
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 272983813

We aim to overcome the immune tolerance against HBV by controlling HBV antigen expression. This will be achieved by inhibiting HBV on the RNA and DNA level via RNAi and CRISPR, respectively. We expect to find that direct targeting of the HBV cccDNA and suppression of the viral transcripts, and hence of viral antigen expression, will restore HBV immunity either on its own or at least after therapeutic vaccination, and that restored B- and T-cell immunity will ultimately clear HBV in vivo. Specific aims include AAV vector fine-tuning in increasingly complex HBV infection models, targeting of checkpoints by RNAi, characterization of potential adverse effects and improving CRISPR safety.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 179: Determinants and dynamics of elimination versus persistence of hepatitis virus infection
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Heads: Professor Dr. Dirk Grimm; Professorin Dr. Ulrike Protzer