In Utero Treatment of Duchenne Muscular Dystrophy with Non-viral Gene Editing

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Grant Award Details

Grant Type:
Quest – Discovery Stage Research Projects
Grant Number:
DISC2-14097
Investigator(s):
Name:
Aijun Wang PhD
Institution:
University of California, Davis
Type:
PI

Disease Focus:
Duchenne Muscular Dystrophy, Skeletal/Smooth Muscle disorders
Human Stem Cell Use:
Other, Somatic Cell
Award Value:
$2,035,544
Status:
Active

Grant Application Details

Application Title:

In Utero Treatment of Duchenne Muscular Dystrophy with Non-viral Gene Editing

Public Abstract:
Research Objective

To develop a lipid nanoparticle/mRNA complex that can safely and efficiently edit muscle stem cells in utero, correct the dystrophin mutation, and develop a treatment for Duchenne muscular dystrophy

Impact

If successful, we will have developed an effective and low-cost treatment for Duchenne muscular dystrophy and a robust method to safely and efficiently edit muscle stem cells in utero

Major Proposed Activities

  • Develop LNP formulations containing either M6P-cholesterol or folate-PEG-DSPE

  • Develop LNP formulations that can efficiently deliver mRNA to MuSCs and muscle fibers in Ai9 mice via in utero injection
  • Correction of the point mutation in the D2-mdx mouse MuSCs by LNP/mRNA complexes in vitro
  • Correct the mutation in D2-mdx mice after in utero injection of base editor mRNA/LNP complexes
  • Evaluate the editing efficiency and DMD phenotypic correction in D2-mdx mice after in utero base editing
  • Correct the point mutation in human DMD patient cells with ABE(NRCH)-LNPs
Statement of Benefit to California:
Duchenne muscular dystrophy is a long-term degenerative disorder that involves extortionate medical expenses, amounting to an annual average cost of over $50,000 per patient. Since our proposed treatment consists of a low-cost, single injection, we predict significant improvements in health care costs and medical treatment plans with the potential to be accessible to low-income patients and patients in underdeveloped and underserved medical communities.

Publications