Syn-FLEX-NES-jRGECO1b AAV (Serotype 8)

Adeno-associated viruses (AAVs) are 20 to 25 nm single-stranded DNA (ssDNA) viruses belonging to the Parvoviridae family. Their genome consists of two genes, rep and cap, flanked by two 145 bp inverted terminal repeats (ITRs) and packaged into a T = 1 icosahedral capsid composed of 60 protein subunits arranged in a precise stoichiometric manner. The cap gene encodes the VP1, 2, and 3 C-terminal overlapping proteins that form the viral capsid, while the rep gene encodes four multifunctional proteins involved in essential tasks of viral replication, such as DNA binding, site-specific endonuclease activity, and helicase activity. Due to its favorable toxicity and immunogenicity profiles, its ability to mediate stable and long-term expression of therapeutic transgenes, and its ability to efficiently transduce both dividing and non-dividing cells, AAV has emerged as an effective gene transfer vector system for gene therapy of inherited and acquired diseases. Currently, all vectors used in clinical trials and approved gene therapy biologics are based on primate AAV. AAV-based gene therapies are entering the therapeutic market, such as Glybera, which received EMA marketing authorization for the treatment of lipoprotein lipase deficiency.