AAV5-hSyn-NULL

AAV vectors are being explored for a variety of therapeutic applications, and they are the most popular viral gene delivery system in clinical trials. In early and late-stage clinical trials, AAV vectors have achieved remarkable success in treating monogenic diseases such as hemophilia, inherited blindness, and muscular dystrophy, and their clinical safety and efficacy have also been recognized. Gene transfer therapies using AAV vectors are rapidly gaining clinical approval for the treatment of congestive heart failure, hemophilia A and B, retinal diseases, X-linked myotubular myopathy, gliomas, glioblastomas, and spinal muscular atrophy (SMA), among others. It is often stated that 13 AAV serotypes (AAV1-13) have been identified to date, but this is only the most studied subset of the hundreds of serotypes or different AAV variants isolated from primates, goats, sea lions, bats, snakes, and other animals. Some of these serotypes have been divided into clades A–F based on shared serological and functional attributes. Among the common variants of AAV vectors, two serotypes, AAV5 and AAV4, show large differences in capsid protein sequences. AAV5 is the most phylogenetically unique, with a capsid protein sequence that is 58% identical to AAV2 and AAV8 and 57% identical to AAV10. In contrast, other serotypes commonly used in gene transfer have higher homology (approximately 80%). The variable regions in the sequence correspond mainly to conformationally distinct loops in the VP structure that have been implicated in receptor binding, transduction efficacy, and antigenicity, and are associated with differences between serotypes in tissue tropism, antigenicity, and the potential for cross-reactive immunogenicity.