AAV DJ-Syn-Cre

Recombinant adeno-associated virus (rAAV) vectors have attracted extensive attention due to their non-pathogenicity, broad tissue tropism, and long-term transgene expression. They have shown great potential in treating a variety of monogenic human diseases, including neurodegenerative and metabolic diseases. Despite these remarkable achievements, the greatest obstacle is the host humoral and cellular immune response. It is believed that this obstacle can be circumvented if the vector dose can be kept to a minimum without compromising its efficacy. Currently, many laboratories are working to achieve efficient transduction at lower vector doses, including: (1) using rAAV vectors with natural tropism for target cells/tissues/organs; (2) rationally designing viral capsid proteins by site-directed mutagenesis and peptide insertion; (3) selecting from a viral library containing millions of chimeric capsids.

Among rAAV variants, rAAV-DJ is a chimeric vector created from a capsid library using DNA shuffling technology. rAAV-DJ was selected in the presence of mixed human antisera and subsequently validated for its high transduction efficiency and ability to evade immune neutralization compared with other serotypes. It is a chimera of serotypes 2, 8, and 9. It differs from its closest natural relative, AAV2, by 60 amino acids. Since its discovery, rAAV-DJ has been used extensively for gene delivery, such as delivering knockout constructs into fetal porcine fibroblasts to generate Fah null heterozygous pigs and mediating gene targeting in keratinocytes by homologous recombination.