CRISPR/Cas9 nanoparticle enabled therapy for Duchenne Muscular Dystrophy in muscle stem cells
Grant Award Details
Grant Type:
Grant Number:
DISC2-08824
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$2,150,400
Status:
Closed
Progress Reports
Reporting Period:
Year 3 NCE
Grant Application Details
Application Title:
CRISPR/Cas9 nanoparticle enabled therapy for Duchenne Muscular Dystrophy in muscle stem cells
Public Abstract:
Research Objective
Gene correction of muscle stem cells
Impact
These studies will develop a gene editing based therapy for one of the most prevalent lethal childhood disorders called Duchenne Muscular Dystrophy.
Major Proposed Activities
Gene correction of muscle stem cells
Impact
These studies will develop a gene editing based therapy for one of the most prevalent lethal childhood disorders called Duchenne Muscular Dystrophy.
Major Proposed Activities
- To identify the best MSNP-CRISPR candidates for CRISPR/Cas9 plasmid delivery in vitro to muscle stem cells
- To identify the best MSNP-STEM candidates suitable for delivery of the optimal chemo attractant that enables stem cell migration in vitro
- To identify the optimal MSNP-CRISPR and MSNP-STEM candidates from biodistribution studies after systemic injection
- To determine the efficiency of MSNP-CRISPR and MSNP-STEM approaches for delivering CRISPR/Cas9 platform to the stem cell niche.
- To identify the MSNP delivery strategy that results in restoration of functional dystrophin protein and improved muscle strength after long-term satellite cell correction or reconstitution.
Statement of Benefit to California:
Duchenne Muscular Dystrophy is a progressive muscle wasting disorder with life expectancy of approximately age 20 with incidence of 1 in 5,000 live male births. Because it is a chronic disorder, this disease is devastating to families, involves extensive medical expenses and loss of employment for caregivers. School-age children require a classroom aid and an IEP. A treatment for DMD could reduce health care costs, time lost from work and burden on the public school system.
Publications
- J Neuromuscul Dis (2017): Creation of a Novel Humanized Dystrophic Mouse Model of Duchenne Muscular Dystrophy and Application of a CRISPR/Cas9 Gene Editing Therapy. (PubMed: 28505980)
- Nat Cell Biol (2018): ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs. (PubMed: 29255171)
