Exon skipping is a technique that is potentially applicable to a variety of genetic diseases because it can remove a small portion of a protein that would have contained a premature stop or a frameshift mutation. This technique, however, will require frequent, long-term delivery of the exon skipping compound (antisense oligonucleotides) to the patient's muscle throughout life. This project will study the systemic delivery method to determine how effective it is at distributing one type of exon skipping oligonucleotide (morpholinos) to the muscle of dogs with muscular dystrophy (the CXMD dog model). Both short-term and long-term delivery to dogs will be tested. These results will help optimize a delivery method for exon skipping oligonucleotides in a large animal model of muscular dystrophy.
*This project was carried out in collaboration with Terence Partridge, Children's National Medical Center (Washington, DC) and Shin'ichi Takeda, National Institutes of Neuroscience (Tokyo, Japan).
**This project was funded jointly by the Jain Foundation, the Foundation to Eradicate Duchenne (FED), the Wellstone Center Network of NIH, the Crystal Ball (Norfolk VA) via MDA, and the Japanese Government.