Novel Therapeutic Strategy to Achieve Upregulation of Dystrophin Isoforms
Abstract
The objective of this project is to achieve a single-vector CRISPR-dCas9 gene activation platform to upregulate near full-length muscle dystrophin isoform (Dp427m) as a therapeutic strategy to compensate for its reduction in candidate dystrophinopathy patients with in-frame deletions. Our lead construct design will be systemically delivered using AAV9 and tested for the optimal dose required to achieve therapeutic upregulation of the dystrophin gene from its endogenous locus in both skeletal and cardiac muscles. A transgenic humanized DMD/BMD mouse model harboring a deletion of exon 45-49 of muscle dystrophin will be generated to enable functional assessment of our construct and the therapeutic potential of upregulating truncated dystrophin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1228959
Entities
People
- Monkol Lek
Organizations
- Yale University