Syn-FLEX-GCaMP6f AAV (Serotype 8)

Adeno-associated virus (AAV) is a small, dependent parvovirus that can be used as a gene therapy vector for the treatment of a variety of inherited and acquired diseases. AAV is a versatile gene delivery system due to its non-pathogenicity, low immunogenicity, and differential tropism for a variety of cell types. This non-enveloped virus is approximately 25 nanometers in diameter and contains a unique linear single-stranded DNA genome. AAV has a 4.8 kilobase pair genome flanked by two copies of 145 bp inverted terminal repeats. To date, approximately 13 different AAV serotypes have been used for gene therapy. AAV serotypes show 55-99% sequence homology but differ in tissue tropism. The amino acids of a particular serotype determine its structural dynamics and tissue specificity. AAV8 is widely known for its high performance in liver transduction and is the preferred vector for liver-targeted gene therapy. AAV8 is used to treat hemophilia A, hemophilia B, familial hypercholesterolemia, and glycogen storage disease type II. AAV8 has been shown to transduce cardiac and skeletal muscle in hamsters and mice. Host cell glycosylation plays an important role in AAV viral entry, tissue selection, and infectivity. These roles are supported in part by the identified AAV receptors, which are often glycans. Heparan sulfate, galactose-terminated N-glycans, and sialic acid are well-known primary receptors for various AAV serotypes. A secondary receptor for AAV8 is the laminin receptor (LamR), a host cell surface glycoprotein. Some AAV serotypes differ significantly in their in vivo performance and secretion efficiency, characteristics that may be influenced by glycosylation status.