Development of gene therapy for pediatric Inflammatory Bowel Disease (IBD) patients with rare and lethal mutations

Based on current research in the field of genetic disorders, gene therapy – through the use of gene editing tools such as CRISPR – is a promising method to rescue defective genes. Stem cells from patient can provide a compelling in vitro model for gene therapy. In this work we are investigating the effects of a mutation causes inflammatory bowel disease (IBD) in both intestinal and pancreatic cell lines.
Interestingly, it has been shown that some mutations, which are highly damaging to the intestinal epithelia, have no apparent detrimental effect on pancreatic cell line. This suggests compensatory mechanism avoiding apoptosis and death in pancreatic cells.
Like the intestine, stem cells in the pancreas also give rise to diverse epithelial cell types. Thus it would be highly advantageous to develop a gene therapy protocol using pancreatic progenitor cell as a proof-of-principle for intestinal epithelia.
However, introduction of corrected sequence of the genome with no base insertion/deletion at the end of DNA double stranded break, resulted from CRISPR-Cas9 nickase activity, is challenging. We are hoping to have site-specific genomic integration of therapeutic transgenes to the defective stem cells in intestinal epithelial.

Faculty Supervisor:

Aleixo Muise

Student:

Partner:

University of Pennsylvania

Discipline:

Life Sciences

Sector:

Education

University:

University of Toronto

Program: