AAV9-CAG-GCaMP6m

Adeno-associated virus (AAV) vectors offer promise for treating disease through gene therapy strategies. Interest in the use of AAV vectors has grown with the approval of Luxturna by the U.S. Food and Drug Administration (FDA) in 2017 and Zolgensma in 2019. Clinical trials using AAV vectors have targeted hemophilia, alpha 1 anti-trypsin deficiency, Duchene muscular dystrophy, and Pompe disease.

The AAV T=1 icosahedral capsid is assembled from 60 structural viral proteins (VPs) VP1, -2, and -3 subunits in a ratio of approximately 5:5:50. The VPs are all products of open reading frames encoding genomic structural proteins, called caps, VP1 (approximately 82 kDa) and VP2 (approximately 73 kDa), which are minor capsid proteins, and VP3 (approximately 61 kDa), which is the major capsid protein. Due to the utilization of both alternative splicing and leaky scanning, when expressed, the individual VPs share a C-terminus that contains the entire VP3, while VP1 and VP2 are N-terminal extensions of VP3. VP1 and VP2 share a region of approximately 73 amino acids (aa) that is extended by an additional approximately 137 amino acids in VP1, termed the VP1 unique region (VP1u). Like most parvoviruses, AAV VP1u contains a phospholipase A2 (PLA2) domain, a calcium-binding loop, and a nuclear localization signal, all of which are required for infection.