Syn-GCaMP6m AAV (Serotype 8)

AAV has been bioengineered to produce rAAV vectors targeting a variety of monogenic diseases, with many therapies either approved or in late-stage development. In rAAV vectors, the AAV genome is replaced by a transgene expression cassette that includes a specialized promoter, the transgene of interest, and a transcriptional terminator, flanked by ITRs. In addition to accommodating the transgene expression cassette, this replacement of viral coding sequences also helps reduce immunogenicity and cytotoxicity. The tissue tropism of the resulting rAAV depends largely on the capsid used, and a variety of natural or engineered capsids are available for targeting different tissues. Optimization of the transgene expression cassette by improved codon usage, CpG depletion, or inclusion of tissue- or cell-selective regulatory elements can further enhance the selectivity and efficiency of transduction. AAV enters the cell via receptor-mediated endocytosis. AAV then traverses endosomal and Golgi compartments and, after endosomal escape, undergoes nuclear transport and uncoating. The single-stranded AAV genome is converted to a double-stranded genome by the activity of cellular DNA polymerases. AAV requires a helper virus (e.g., adenovirus, herpes simplex virus) to facilitate gene expression and viral replication. In the presence of a helper virus, AAV can undergo a productive infection characterized by genome replication, viral gene expression, and virion production. In the absence of a helper virus, AAV can establish latency by integrating into the adeno-associated virus integration site 1 (AAVS1) on chromosome 19 and other chromosomal locations mediated by the Rep protein. Currently, no confirmed cases of rAAV-mediated genotoxic events in humans have been reported to date.