Developing a universal CRISPR gene therapy approach to treat C9orf72 ALS
Grant Award Details
Grant Type:
Grant Number:
DISC2-16738
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Cell Line Generation:
Award Value:
$2,740,592
Status:
Active
Grant Application Details
Application Title:
Developing a universal CRISPR gene therapy approach to treat C9orf72 ALS
Public Abstract:
Research Objective
Development of a CRISPR genome editing therapy for ALS caused by C9orf72 and the delivery vehicle required to bring this novel therapy to patients.
Impact
A cure for neurodegenerative disease has never been achieved. CRISPR gene therapy for C9orf72 repeat expansion mutations could arrest or prevent C9-ALS/FTD.
Major Proposed Activities
Development of a CRISPR genome editing therapy for ALS caused by C9orf72 and the delivery vehicle required to bring this novel therapy to patients.
Impact
A cure for neurodegenerative disease has never been achieved. CRISPR gene therapy for C9orf72 repeat expansion mutations could arrest or prevent C9-ALS/FTD.
Major Proposed Activities
- Determine how to efficiently remove the C9orf72 repeat expansion from the genome of patient iPSCs using CRISPR
- Determine the genomic off-target effects of CRISPR editing of the C9orf72 gene in patient iPSCs
- Compare lipid nanoparticles (from the Clelland lab) and novel AAVs (from the Deverman lab) for the ability to delivery CRISPR reagents with broad coverage of the brain and spinal cord
- Determine dosing of candidate therapeutic in the C9-BAC ALS model system in vivo
- Determine biodistribution and biosafety of candidate therapeutic in C9-BAC ALS model system in vivo
Statement of Benefit to California:
ALS is a fatal neurodegenerative condition with a high cost to patients, their carers and the healthcare system. Arresting or preventing the onset of ALS in patients with mutations in C9orf72 would usher in the next phase of personalized and genomic medicine. We aim to change the course of ALS for patients, their loved ones and our healthcare system throughout California and worldwide.
