Delivery of splice switching oligonucleotides using exosomes for the treatment of spinal muscular atrophy
Principal investigator(s) :Professor Matthew Wood
Institution :University of Oxford, UK
Grant Type:Operating Grant
Call number :4
Start year :2012
Duration :2 years
Spinal Muscular Atrophy is treatable with a gene therapy called “splice switching oligonucleotides" (SSO) to modify the splicing of the “back-up” gene SMN2 such that it produces more functional protein. SMA animal models treated with very high doses of SSOs directly injected into the central nervous system were able to significantly extend survival. However, translating animal studies to human clinical trials will require better targeting and more efficient uptake of SSOs in affected tissues, namely skeletal muscle, motor neurons and the heart, all of which are difficult targets for delivery of SSOs. Professor Wood and his team developed a new form of drug delivery using exosomes (the body’s own transport system for transporting molecules between cells) to carry gene therapies across the blood-brain barrier for the treatment of Alzheimer’s disease in animals (this was reported in the UK by the BBC in March 2011). Exosomes have proven to be safe and effective for systemic delivery of nucleic acid-based gene therapies and this grant will be used to look at this form of drug delivery to treat SMA.