CAG-FLEX-jGCaMP7s AAV (Serotype 9)

Gene therapy research relies on the use and optimization of safe nonreplicating viral vectors. The choice of viral vector depends on the tropism of the virus and its ability to consistently express the therapeutic gene in the target cells. A key challenge to overcome in designing an effective gene therapy approach to treat neurodegenerative diseases is access to the central nervous system (CNS), which must be achieved by crossing the blood-brain barrier or by direct injection into the CNS. Serotype 2 of the adeno-associated viral vector (AAV2) has become the vector of choice for neurological clinical trials due to its neuronal specificity and limited immune response. However, its modest transduction levels and lack of non-neuronal transduction are also considered limitations. For this reason, many groups are currently investigating other serotypes to characterize their individual properties. Among them, adeno-associated viral serotype 9 (AAV9) has attracted great interest as a candidate vector for central nervous system (CNS) gene therapy, as AAV9 can cross the blood-brain barrier from the blood circulation and transduce neurons and glial cells. In fact, several studies have shown that intravenous administration of AAV9 successfully reversed disease phenotypes and prolonged survival in mouse models of spinal muscular atrophy and amyotrophic lateral sclerosis.