Generation of therapeutically effective stem cell transplants by targeted genome modification (C09)

• Subject Area: Hematology, Oncology
• Term: from 2011 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 24899777

As an alternative to the reversible delivery of molecules, targeted genome modification is a complementary strategy to prevent insertional mutagenesis. This could enable gene repair with subsequent autologous transplantation in case of hereditary disease or allow the generation of safe cellular products as used in many projects of CRC738. In the past funding period, the project demonstrated targeted genome correction into a ¿safe genome harbour¿ by designer-nuclease assisted homologous recombination for the X-linked chronic granulomatous disease (X-CGD). The aim for the next funding period will be to use CRISPR¿Cas9 based strategies for selected examples relevant for the generation of therapeutically effective stem cell transplants by targeted genome modifications. They will first try to vectorize the CRISPR-Cas9 system for application in stem cells. They will then use the technology to modify hematopoietic stem cells to improve HSC expansion and repopulation. Finally, they will use the technology for genome editing by either inserting new genes into safe harbours or by gene correction as exemplified for X-CGD.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 738: Optimisation of Conventional and Innovative Transplants
• Applicant Institution: Medizinische Hochschule Hannover
• Co-Applicant Institution: Helmholtz-Zentrum für Infektionsforschung (HZI)
• Project Heads: Professor Dr. Toni Cathomen, until 5/2012; Professorin Emmanuelle Charpentier, Ph.D., from 7/2015 until 9/2015; Professor Dr. Axel Schambach