This week we profile a recent publication in Molecular Therapy: Methods & Clinical Development from Zeinab Mohanna (pictured) in the laboratory of Dr. Elizabeth Simpson at the Centre for Molecular Medicine and Therapeutics at BC Children’s Hospital.
Can you provide a brief overview of your lab’s current research focus?
The overall research goal in Simpson lab is to develop gene-based therapies for diseases of the brain and eye. The immediate goal is to use recombinant adeno-associated viruses to deliver therapies for treatment of mouse models of human disease. Currently, we are developing cell-type-specific promoters to use in viruses, engineering better mouse models, and developing gene augmentation and genome editing (CRISPR/Cas9) therapies focused on curing aniridia. Aniridia is a rare genetic disease that reduces vision from birth and progresses to blindness by adulthood due to unmet therapeutic needs. Research by the Simpson lab, and others, has shown that there is a therapeutic window available to limit vision loss. Curing the mouse model of aniridia will lay the conceptual and practical foundation upon which human gene therapy can be designed.
What is the significance of the findings in this publication?
In this study, we created a new mouse model for aniridia that allows quantification of genome-based therapies. We then successfully developed an allele-distinguishing CRISPR strategy to correct this mouse’s germline mutation and completely rescued the blindness.
What are the next steps for this research?
Our publication laid the foundation for developing a somatic gene therapy (which is non-heritable) for aniridia. In future studies, we aim to package our CRISPR strategy in recombinant adeno-associated viruses and deliver it to the somatic cells of young mouse eyes to model gene therapy in recently diagnosed children with aniridia.
This work was funded by:
- Canadian Institutes of Health Research grant (2OR77895)
- The Canada Foundation for Innovation (grant 2OR76139)
- BC Children’s Hospital Research Institute (grant CRG74760)
- Brain Canada Foundation through the Canada Brain Research Fund, with the financial support of Health Canada and BCCHR Institute
- The University of British Columbia Four Year Doctoral Fellowship and Graduate Student Initiatives, and the CIHR Canadian Graduate Scholarship
