About

Sara K. Powell joined the joined the Department of Pediatrics as an Assistant Professor in the Division of Genetics and Metabolism on September 1, 2022. Dr. Powell earned her PhD in Genetics and Genomics from Duke University in 2014. Dr. Powell began her post doctoral training with the UNC-CH Gene Therapy Center in 2014 and has been a Senior Research Assistant in the McCown Lab since 2021.

Dr. Powell’s research focus is on iIntrinsic AAV proteins and their potential roles in AAV biology that can be applied to AAV gene therapies in the Central Nervous System (CNS).

AAV basic biology

Adeno-associated virus (AAV) has become the vector of choice for gene therapy treatments. AAV’s dominance is due in part to decades of research on its biology here at The UNC-CH Gene Therapy Center. Now that the therapeutic potential of gene therapy and AAV gene therapy has been realized, a greater understanding of the virus is required to generate safer, more efficacious treatments. My lab studies intrinsic AAV proteins and their potential roles in AAV biology that can be applied to AAV gene therapies in the Central Nervous System (CNS). One such AAV protein is VP1 which is a subunit of the capsid, but we focus on the internalized unstructured region that is unavailable to cellular receptor binding. This region of VP1 can be changed to alter transgene expression in vivo, and we are working to harness this and learn about its mechanism. Another AAV intrinsic protein is MAAP (membrane-associated accessory protein) which is encoded in the same gene as VP1 but from an alternate reading frame. While MAAP was first described to function during AAV vector production, we found that it can mediate AAV transgene expression in vivo. Therefore, we work to understand MAAP biology in vivo and how to apply what we learn to develop AAV gene therapies for the CNS.

AAV gene therapy for CNS

My lab has collaborated with other labs to generate AAV novel vectors for epilepsy, ALS, and Alzheimer’s by targeting oligodendrocytes, pericytes, and neurons using our findings from AAV basic biology and capsid libraries.