Project 466428

Gene therapies are a novel cure for rare genetic disorders. Currently, Canadian patients with inherited immune disorders eligible for gene therapies must travel to other countries for treatment, where cost can be over $2 million/patient. There is a significant need to develop and make these therapies accessible in Canada. Utilizing a pilot clinical trial, this project will pave the way for a collaborative framework for advanced therapies in Canada. CD3delta SCID is an ideal candidate disease for a Canadian pilot, as it is much more common in Canada due to a high incidence in a founder population living here. Patients have a severe defect in their immune system and present in infancy with life threatening infections if not treated with bone marrow transplant. Overall survival is only 61-67% and most survivors suffer significant complications. Gene therapy for other types of SCID have been shown to be safer, with 100% survival and reduced complications. We have collaborated with Dr. Donald Kohn, an expert in gene therapies at the University of California, Los Angeles, to develop a gene therapy for CD3delta SCID. Preliminary work has shown base editing, a newer technique, to be optimal compared to other gene editing strategies. In our lab models, it is much more efficient and precise at correcting the defect. Testing on bone marrow cells from an Alberta patient with CD3delta SCID demonstrated correction of the mutation and growth of T cells . We propose a multicenter Canadian clinical trial to test gene editing in patients with CD3delta SCID, whereby we would collect their bone marrow cells, edit the gene in the lab, then reinfuse the cells back into the patient with long term follow up for clinical outcomes and immune reconstitution. This trial represents a scientific landmark as one of the first gene therapy trials using a base editing strategy and will develop a Canadian pipeline for precision medicine for rare disorders.