CAG-FLEX-GCaMP6m AAV (Serotype 8)

Although both viral and nonviral vectors have been widely used for CNS gene therapy, viral vectors, including adeno-associated virus (AAV) and lentivirus, are generally more efficient than nonviral vectors in delivering genes to target cells. Cell specificity can be controlled by intrinsic properties of the vector or by the specificity of the promoter controlling transgene expression. AAVs have emerged as the most promising tool for CNS gene transfer due to their ability to transduce both dividing and non-dividing cells and induce stable, long-term gene expression in the absence of inflammation and/or toxicity. As neurons are post-mitotic cells, the ability of AAV vectors to transduce non-dividing cells is critical in gene therapy for neurodegenerative diseases. In particular, AAV serotype 8 (AAV8) has been shown to be one of the most efficient vectors in certain structures of the CNS, with the highest transduction rates in the striatum compared to other serotypes, without neurotoxicity. In addition, active transport of this serotype along axons has been observed in multiple studies in different animal models. One of its limitations is its cloning capacity due to its small size (4.7 kb), however, the use of minimal specific promoters facilitates the expression of larger genes or the co-expression of multiple genes from the same vector. The use of AAV as a delivery vehicle has been demonstrated to achieve robust and long-term gene expression in preclinical and clinical studies.