CleanCut: Developing a human in vitro model to assess the safety of gene edited human haemopoietic stem cells

Gene editing of human haemopoietic stem cells (hHSCs) using designer nucleases (e.g. CRISPR) has the potential to cure some blood-related diseases caused by mutations in a single gene. However, off-target gene modifications can generate cells with oncogenic potential. In vivo studies (e.g. in mice) to assess the tumourigenicity of gene edited (GE) products require large numbers of animals, are costly, time consuming and are not always predictive of human safety. 

Sponsored by Bayer, Novartis and Takeda, the key objective of the CleanCut Challenge is to develop a human in vitro model for use in the safety assessment of GE-hHSCs to replace in vivo tumourigenicity studies. 

Phase 2 funding has been awarded to a multi-disciplinary team led by Dr Alessandro Rotilio (MOAB srl, a spin-off of Politecnico di Milano incubated by Hub-Initio). The team will develop a dual model system consisting of 3D organotypic models of the haemopoietic niche and the lymph node using a miniaturised optically accessible bioreactor (MOAB). Assessment of normal and aberrant tumourigenic behaviour of cells will be conducted by characterisation of the circulating cells.  

Full information about this Challenge is available on the Innovation Platform website.