AAV DJ/8-Syn-GFP

AAV serotypes show significant differences in transduction efficiency and tissue tropism, making them highly promising vectors for human gene therapy. AAV has a single-stranded DNA (ssDNA) genome, which is mostly replaced in gene therapy vectors. The DNA is surrounded by a protein coat composed of 60 capsid proteins (three variants), the structure of which was first solved by X-ray crystallography for the type species AAV-2. Functions such as cell attachment, entry, and immune evasion are associated with this capsid coat. Several serotypes, including AAV-2, bind to cell surface heparan sulfate proteoglycans (HSPGs), which until recently were considered the "primary" entry receptor.

AAV-DJ is a recombinant variant selected for its resistance to human neutralizing sera and improved liver tropism, and is a chimeric mixture of serotypes 2, 8, and 9. The low-resolution (5 Å) structure by cryo-electron microscopy (cryo-EM) as well as functional characterization show that it is very similar to AAV-2. AAV-DJ/8 is a mutant of AAV-DJ in the heparin binding domain (HBD). AAV-DJ/8 differs from its closest natural relative (AAV-2) by 60 capsid amino acids. In culture, recombinant AAV-DJ/8 vectors outperformed eight standard AAV serotypes, while in the liver, they far outperformed AAV-2.