AAV9-EF1a-FRT-GFP

Adeno-associated virus (AAV) is a small, nonenveloped, single-stranded DNA (ssDNA) virus belonging to the genus Dependovirus in the family Parvoviridae. Over the past few decades, recombinant AAVs have emerged as promising vectors for therapeutic gene delivery because of their ability to package and express foreign genes in a wide range of tissues in the absence of active cell division and to do so without any associated pathogenicity. Twelve different AAV serotypes (AAV1 to AAV12) are known from humans and nonhuman primates, and many recombinant species have been isolated. Sequence identity between the capsid proteins of the 12 serotypes ranges from ∼55% to 60% (e.g., between AAV4 and AAV5 and between these two serotypes and other serotypes) to >99% (e.g., between AAV1 and AAV6).

AAV9 is a human AAV serotype that has greatly improved transduction efficiency in cardiac and skeletal muscle, liver and pancreatic tissues, and the eye compared with other serotypes. Similar to other AAVs, AAV9 can transduce non-dividing cells, including hepatocytes, which normally express Factor IX (FIX). In a hemophilia B study, AAV9 vectors expressing FIX were able to transduce the liver without induction of pro-inflammatory cytokines, unlike similar experiments using lentiviral vectors. Given its tissue tropism, AAV9 is being developed for a variety of therapeutic gene delivery applications, such as cardiac and ocular diseases and coagulation disorders, such as hemophilia A and B. AAV9 can also cross the blood-brain barrier and, of all AAVs, targets the central nervous system with high efficiency.