AAV DJ/8-GFAP-GFP

AAV is a non-enveloped eukaryotic virus that has been closely related in propagation and evolution to its close relative, the adenovirus. The AAV genome is relatively small (4.7 Kb) and contains a replication element (rep) and a capsid element (cap), flanked by inverted terminal repeats (ITRs) that form a hairpin-like secondary structure. The ITRs, while providing a protective function, also confer the ability of the (conjoined) AAV episome to survive in mammalian cells. Compared to wild-type AAV, recombinant AAV used for gene therapy lacks the rep and cap elements, which are replaced by therapeutic and/or reporter genes. The AAV life cycle after infection is lysogenic unless adeno accessory proteins are present, allowing a productive lytic cycle to occur.

Despite the favorable genetic properties of AAV vectors, a major drawback is their low transduction efficiency in target tissues. The broad tropism of AAV for a variety of tissue types significantly reduces the transduction efficiency of AAV vectors. Using new technologies, recombinant AAV (rAAV) vectors with higher tissue specificity and transduction efficiency have been identified. DNA family shuffling represents the next generation of pseudotyping technology that allows the construction of complex chimeric AAV capsids from up to eight serotypes. Compared to AAV2, these mixed serotypes (e.g., AAV-D/J and AAV-DJ/8) not only have higher efficiency and specificity in liver transduction but also provide a new platform for peptide display and directed evolution of AAV vectors.