AAV4-Null

Adeno-associated virus Serotype 4 (AAV4) is considered one of the most antigenically distinct serotypes. It is reported to originate from NHPs, primarily African green monkeys, as antibodies against its viral particles have been detected in their sera. Studies on the structure of AAV4 have shown that its capsid surface topology has significant similarities to human parvovirus B19 and Aleutian mink disease virus. AAV4 uses a-2,3-O-linked sialic acid for cell binding and infection. Therefore, mucin columns can be used to purify AAV4 due to its ability to bind to sialic acid residues in mucin. In addition, due to the lack of heparin binding activity, this serotype cannot be purified using heparin column affinity chromatography as AAV2, however, ion exchange chromatography procedures have been developed and shown to have high purification efficiency. The only reported post-translational modification (PTM) of rAAV4 is ubiquitination of its capsid protein. AAV4 is reported to be able to transduce human/NHP cells as well as cells of murine and canine origin. The specific tropism of AAV4 enables it to transduce specific cell types in the mammalian central nervous system (CNS), primarily ependymal cells. In addition, following subretinal delivery, AAV4 has demonstrated stable transduction of retinal pigment epithelial (RPE) cells in rodent, canine, and non-human primate models, a unique feature due to its capsid specificity. In murine models, AAV4 has also demonstrated significant transduction rates of kidney, lung, and heart cells.