Recent advances in genome engineering technologies based on the CRISPR-associated RNA-guided endonuclease Cas9 are enabling the systematic interrogation of genome function. Using this system, DNA sequences within the endogenous genome and their functional outputs can be easily edited or modulated. Cas9-mediated genetic perturbation is simple and scalable, empowering researchers to elucidate the functional organization of the genome at the systems level and establish causal linkages between genetic variations and biological phenotypes . Recently, application of CRISPR/Cas9 system has become popular for therapeutic aims such as gene therapy.
We are using this platform to define a map of druggable genetic dependencies/essentialities across a number of selected cell lines; some of which are expected to be clinically actionable with currently available small molecules or other drugs. In parallel, we are seeking to understand molecular pathways that control expression of proteins involved in carcinogenesis and/or immune system evasion by tumours.
Screening and gene editing technologies are used to screened for therapeutic modulation targets in human primary cells. CSHM scientists are looking for targets to control activation of immune responses in disease settings such as cancer. Primary cell screening, includes isolation of cells of interest of hematopoietic or non-hematopoietic origin and in vitro culturing and/or expansion. The ability to scale-up the expansion of cells is a major challenge in cell therapy. Scientists are establishing a variety of culturing protocols to support the expansion of various cell types. Currently, there is a focus on conventional T cells, regulatory T cells and NK cells.