Development of an innovative CRISPR-Cas13-based therapeutic approach against hepatitis E virus (HEV-CUT).

• Applicants: Dr. Yannick Brüggemann; Professor Dr. Eike Steinmann
• Subject Area: Gastroenterology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 522354957

Viral infections are a major cause of disease, mortality and economic loss worldwide. In particular, RNA viruses cause a wide range of human diseases and represent a global health problem. To date, effective antiviral drugs are not available for a variety of clinically relevant viral pathogens, including the hepatitis E virus (HEV). HEV-CUT will evaluate the CRISPR/Cas13 system as an innovative genetic intervention strategy against HEV. We will design and screen CRISPR RNAs (crRNAs) targeting conserved regions of the HEV genome to identify broadly active crRNAs targeting different HEV variants and prevent the emergence of resistant variants. Furthermore, DNA-free virus-like particles will be used in combination with authentic cell culture systems to study therapeutic application of the CRISPR/Cas13d system under physiologically relevant conditions. Thereby, HEV-CUT will provide a proof-of-concept study using a CRISPR-Cas13-based approach to target the hepatitis E virus and create a platform that enables rapid and flexible adaptation to different virus variants as well as efficient therapeutic delivery.

• DFG Programme: Research Grants