Charles Gersbach, assistant professor at Duke University in Durham, N.C., was awarded an MDA research grant totaling $300,000 over a period of three years to develop a new approach for gene therapy in Duchenne muscular dystrophy (DMD).
The most common gene therapy approaches in DMD involve supplying new dystrophin genes (the dystrophin gene is mutated in the disease), allowing the new genes to integrate into existing chromosomes or to remain outside the chromosomes. The first approach can potentially disrupt other genes, while the second only provides temporary therapy that requires frequent re-administration, raising risks.
“An exciting alternative to these approaches is a new technology, called genome editing, that can target the addition of therapeutic genes to specific sites in the genome or directly repair the disease-causing mutations [in existing genes],” says Gersbach. The technique is already being tested in early-stage clinical trials in HIV and cancer.
Genome editing holds the potential for fixing mutated genes permanently. The approach may apply to all genes and all kinds of mutations, including large deletions.
In this project, the overall objective is to engineer and test enzymes called nucleases to see if they can either deliver the dystrophin gene or repair existing mutant dystrophin gene sequences. The enzymes will be tested in cultured cells from DMD patients and in a mouse model of the disease.
“New technologies for gene delivery and gene modification are overcoming the challenges of translating gene therapy into correction of genetic diseases,” Gersbach says. “These technologies are expected to lead to dramatic advances in gene therapy in the next few years.”
Funding for this MDA grant began August 1, 2013.