Thérapie génique par édition génique des cellules souches hématopoïétiques pour le traitement des maladies immunitaires et hématologiques

 

Fabien Touzot

Centre hospitalier universitaire Sainte Justine

 

Domaine : génétique humaine

Programme Chercheurs-boursiers cliniciens - Junior 1

Concours 2018-2019

My research program aims to bring to the patient's bedside gene therapy of hematopoietic stem cells (HSC) for diseases of the blood and immune system. HSCs are the cells that originate the different blood lines (white blood cells, red blood cells and platelets). I am currently developing a system of genetic modification of these cells using "molecular scissors": the nucleases of the CRISPR system. These "scissors" allow the DNA of the cells to be cut in specific locations resulting in an activation of the DNA repair systems. By using a DNA repair mechanism called homologous recombination, which allows the repair of a DNA cut from a DNA template, it is possible to introduce changes in the genetic sequence in a precise manner. This genetic engineering technique therefore has the potential to modify with precision any gene in the genome.

My research program aims to develop this genetic modification approach to treat two pathologies: (i) sickle cell disease, a hereditary blood disorder caused by a genetic mutation of the hemoglobin gene, and (ii) HIV infection, a well-known acquired infectious disease, by making the white blood cells originating from genetically gene-modified HSCs resistant to the virus. My program will provide the pre-clinical data essential to the development of clinical trials for these pathologies in Canada. In addition, the development of an effective gene editing strategy of HSC may be subsequently applied to other hereditary or acquired human diseases involving blood cells