Children’s Research Institute Seminar Series

Engineering intrinsic AAV proteins for safer gene therapies

Sara Powell, PhD

Assistant Professor of Pediatrics
UNC Pediatric Genetics & Metabolism &
The Center for Molecular Medicine

3116 Mary Ellen Jones

Lunch Provided

or

Zoom Details Upon Request

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. Dr. Powell’s 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 they 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 Dr. Powell’s team is 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, they found that it can mediate AAV transgene expression in vivo. Therefore, her lab works to understand MAAP biology in vivo and how to apply what they learn to develop AAV gene therapies for the CNS. Dr. Powell’s lab has also collaborated with other labs to generate AAV novel vectors for epilepsy, ALS, and Alzheimer’s by targeting oligodendrocytes, pericytes, and neurons using their findings from AAV basic biology and capsid libraries.

Open to All:

You don’t need to be a CRI member to present or participate. Have an idea to share? We’d love to hear from you—contact childrensresearch@med.unc.edu