Present and future of adeno associated virus based gene therapy approaches.

During the last 20 years, transgenic constructs based on adeno associated virus (AAV) have been tested in disease models and proved their efficacy to revert a wide range of pathologies without major side effects. Based on these results, up to 20 clinical trials have been set up to prove therapeutic effect of AAV vectors on neurodegenerative diseases, retinopathies and neuromuscular diseases, among others. It has been shown that AAV vectors support localized long-term, gene expression in the central nervous system, and that restoration of visual function can be achieved in Leber's congenital amaurosis retinopathy. The clinical trials also highlighted new challenges for AAV mediated gene transfer, such as the circumvention of T-cell response to transduced cells. Currently, miniaturized and codon-optimized transgenes, exon skipping cassettes, novel tissue-specific promoters and vector chimeras with tissue-selective tropism are being tested to improve the efficiency and safety of transgene delivery, as required to meet pharmaceutical industry standards. The aim of this review is to revise the latest patents and news on AAV vectors, in order to summarize the state of the art and the potential issues that still need to be faced by pharmaceutical companies for successful gene transfer and commercialization of AAV-based drugs.