Grant: CIHR Fellowship

Pediatric genetic disorders are individually rare but collectively frequent, affecting approximately half a million children in Canada. Dyskeratosis congenita is a rare genetic disease caused by mutations in genes involved in the protection of the distal ends of chromosomes. These distal chromosome regions are known as telomeres, and they ensure the integrity of the genetic material. A promising way to understand and treat this disease is to precisely modify the pathogenic DNA sequence in human blood stem cells, a process known as therapeutic genome editing. As part of this postdoctoral research project, I propose to adapt a state-of-the-art genome editing technology called prime editing to identify and characterize new pathogenic mutations to better understand dyskeratosis congenita. I also propose to develop a universal therapeutic prime editing approach to treat all known dyskeratosis congenita mutations in a defective gene named TINF2 in blood stem cells. More broadly, the knowledge gained during this project should facilitate the interrogation of blood stem cells and the development of therapeutic prime editing approaches for severe blood disorders afflicting children.