Melissa Spencer, professor of neurology and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA has received a $999,999, three-year grant from the California Institute for Regenerative Medicine to develop a new delivery method to improve gene therapies for neuromuscular disorders. Spencer will partner with co-investigator April Pyle, professor of microbiology, immunology and molecular genetics, and Michael Emami, a graduate student in the Spencer lab, to carry out the study.
Gene therapies treat genetic disorders by modifying the genes inside of a patient’s own cells. Traditional gene therapies deliver a healthy gene to replace a malfunctioning or missing gene that is causing disease, while CRISPR Cas9 enables researchers to fix the disease-causing gene directly by snipping out and replacing errors at specific sites in its DNA sequence.
Most gene therapies use modified viruses, called viral vectors, to deliver their genetic cargo into patients’ cells. The genetic material that these viral vectors deliver is encased in a protein shell called a capsid. Capsids play a huge role in a viral vector’s success – they influence its ability to get into the right cell types efficiently.
Spencer and Pyle have been working together to develop gene therapy approaches for neuromuscular conditions like Duchenne Muscular Dystrophy for over a decade. In order to develop a lasting treatment for these conditions, the genetic correction needs to occur in muscle and sometimes in neural stem cells.
“For inherited neuromuscular conditions like Duchenne and Walker Warburg syndrome, you want to be able to deliver the gene therapy to both affected stem cell populations very early in a child’s development,” said Spencer, who is also Neuromuscular Program Director in the UCLA David Geffen School of Medicine. “The problem is, there is no platform available that can deliver genes to both of those cell types.”
The new CIRM grant will support Spencer and Pyle’s efforts to overcome this obstacle by identifying new capsids that are capable of delivering genetic cargo into both muscle and neural stem cells. Their ultimate hope is that through this work, they will develop a library of viral vectors that are highly efficient at targeting specific types of cells. This would open up the applicability of gene therapy to a wider range of diseases and by making these treatments more efficient, make them more accessible to patients.