Dr. Wilson is a Penn Medicine physician.
Description of Research Expertise
Research Interests
Dr. Wilson’s laboratory focuses on the development of gene transfer vectors and their application in the treatment of inherited and acquired diseases. Characterization of these novel viral isolates has yielded important insights into basic virology. More importantly, recombinant versions of these viruses have proven to be useful as improved gene transfer vehicles to a variety of targets such as the liver, cardiac and skeletal muscle, and the brain.
Description of Research
Dr. Wilson is an innovator and pioneer in the field of gene therapy. In a career spanning four decades, he has identified, isolated, and developed virus-based vectors for in vivo gene therapy. His laboratory is responsible for discovering a new family of endogenous adeno-associated viruses (AAV) that have become best-in-class for in vivo gene therapy vectors. His research efforts and novel technology have contributed to successful clinical programs of in vivo gene therapy for rare monogenic diseases developed by other companies, including Glybera® for familial lipoprotein lipase deficiency (AAV1), Luxturna® for RPE65-mediated retinal dystrophy (AAV2), and Zolgensma® for spinal muscular atrophy (AAV9). More recently, his laboratory demonstrated for the first time therapeutic in vivo genome editing in a large animal model, thus extending the therapeutic potential of the AAV platform.
During the early 2000s, Dr. Wilson found that AAV genomes are prevalent in primates; characterization of these novel capsids revealed an expanded family of viruses that have great therapeutic promise (1-3). For example, the rhesus isolate AAV8 has shown improved gene transfer to liver, muscle, and photoreceptors (1, 4) whereas the human isolate AAV9 is capable of crossing endothelial and blood-brain barriers that enable it to target the heart and central nervous system (5, 6). Recent work in Dr. Wilson’s laboratory has highlighted how specific AAV-protein interactions in endothelial cells enhance the ability of AAV to cross the blood-brain barrier (7); such work may prove instrumental in the development of new AAV-based therapies for genetic diseases which affect the central nervous system.
Dr. Wilson aims to expand gene therapy to also treat acquired diseases and other conditions, such as deploying AAV-based therapies to treat influenza (8) and central nervous system metastases located beyond the blood-brain barrier (9). Novel applications of the AAV platform include prophylaxis against subsequent organophosphate poisoning, potentially offering protection in biowarfare (10). Dr. Wilson is also pursuing in vivo genome editing. In a world-first, his laboratory recently demonstrated efficient and stable in vivo gene editing in liver cells in non-human primates that resulted in reduced levels of circulating PCSK9 and serum cholesterol; this work has important implications in the treatment of cardiovascular disease (11).
Translational research efforts are ongoing in his laboratory across a portfolio of lysosomal storage diseases, neurodegenerative diseases, infantile epilepsies, and liver metabolic diseases. A robust, discovery-oriented research program in virology, vector engineering, and gene editing complements the translational portfolio and informs the development of next generation vectors and therapies.