About

The McCown laboratory focuses upon the development of safe, effective gene therapies for the treatment of neurological disorders with a focus upon improving specific therapeutic genes as well as the discovery of clinically relevant novel AAV capsids. On the therapeutic gene side, we have discovered a means to express and constitutively secrete AAV vector derived gene products into the CNS interstitial space, leading to a means to suppress seizure activity. On the capsid side, we have used AAV capsid shuffling and directed evolution to discover a novel capsid that selectively crosses the seizure compromised blood-brain barrier, and a novel AAV capsid that exhibits a dramatic shift in in vivo AAV tropism away from neurons and towards oligodendrocytes. Using this oligodendrocyte preferring capsid we were able to reprogram oligodendrocytes in the brain to functional neurons. With my colleague Dr. Powell, we recently established that the AAV capsid can interact with in vivo gene expression in the brain. Thus, the major focus of the lab entails leveraging a basic understanding of AAV vectors in order to significantly advance CNS gene therapy for neurological disorders.