AAV9-CAG-GCaMP6s

Adeno-associated viruses (AAVs) are single-stranded DNA (ssDNA) T=1 icosahedral viruses belonging to the Dependoparvovirus genus of the family Parvoviridae. The vast majority of the Dependoparvovirus genus members are capable of successful replication in nondividing (non-S-phase) cells due to helper activity provided by concurrent larger DNA virus infection. Currently, 13 human and non-human primate AAV serotypes, in addition to AAV5, have been classified as AAV species A. In addition, more than 100 other variants have been isolated from human and non-human primate tissues and samples. AAV species A encode capsid proteins (VPs) with sequence identities of at least 50% and often >80%. Despite the high degree of conservation of VP sequences, AAVs differ in host serum protein interactions, cellular receptors, and trafficking and transduction efficiency in a wide range of tissues. In addition, AAVs are able to readily package genomic and non-genomic ssDNA but have not been associated with any pathology. Together, these properties have led to the development and use of AAV as a gene therapy vector for a variety of monogenic diseases, resulting in AAV-mediated gene therapy for clinical use.

AAV9 is one of the most promising serotypes for gene therapy applications because it has both wild-type (WT) and recombinant construct capsid properties. AAV9 can transduce a variety of tissue types, including cardiac and skeletal muscle, liver, pancreas, and eye. In addition, AAV9 can cross the blood-brain barrier and target the central nervous system with higher efficiency than other AAV serotypes. In addition, AAV9 has a significantly lower seroprevalence in the human population compared to the other two commonly used therapeutic vector serotypes, AAV1 and AAV2, making it a more ideal candidate for therapeutic applications.