Local immunomodulation by viral vectors and genetic modifications (A02)

• Subject Area: Immunology ; Virology
• Term: since 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213602983

The aim of this project is to develop strategies of local immunomodulation to protect the xeno-heart and facilitate long-term engraftment. Components encoding immunomodulatory agents are delivered either by recombinant adeno-associated viral vectors (rAAV), micro-RNAs, small hairpin (sh) RNAs or by genetic modifications of the donor animal. We plan to downregulate pro-inflammatory targets (e.g. the inflammasome NLRP3), increase expression of anti-inflammatory targets (e.g. the “don’t-eat-me” signal CD47) and evaluate the effect of local T cell co-stimulation blockade via LEA29Y in order to minimise rejection mechanisms. The targets are investigated in vivo in pig models of ischemia/reperfusion and in a heterotopic abdominal heart allotransplantation model that was established within a Young Investigator Project of the last funding period.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 127: Biology of Xenogeneic Cell and Organ Transplantation - From Bench to Bedside
• Applicant Institution: Ludwig-Maximilians-Universität München
• Project Heads: Dr. Andrea Bähr; Professorin Dr. Rabea Hinkel, until 12/2020; Professor Dr. Christian Kupatt; Professor Dr. Sebastian Michel; Professor Dr. Peter J. Murray