Investigating gene editing approaches to correct G6PD mutations and potentially cure G6PD deficiency at its genetic source.
Simulating correction of the G6PD Mediterranean (S188F) mutation
The molecular scissors that enable precise genome editing
Targets specific DNA sequence
Multiple strategies for correcting G6PD mutations
Creates double-strand breaks for gene knockout or HDR-mediated correction.
Directly converts one base to another without double-strand breaks.
"Search and replace" editing that can make any substitution or small indels.
Path from laboratory research to potential clinical application
Design guide RNAs targeting common G6PD mutations. Computational prediction of off-target sites using Cas-OFFinder and CRISPOR.
Test editing efficiency in patient-derived cells. Validate correction of enzyme activity using G6PD activity assays.
Develop LNP or viral delivery systems for hematopoietic stem cells. Optimize for bone marrow targeting.
Animal model studies to assess safety, biodistribution, and long-term efficacy of gene correction.
Gene therapy for G6PD raises important bioethical questions about germline editing, access equity, and informed consent. My research includes studying these ethical frameworks alongside the science.
I'm currently using computational tools to design and evaluate guide RNAs for correcting the G6PD Mediterranean mutation using base editing.