In vivo tissue-tropism of adeno-associated viral vectors

• AAV is a non-pathogenic virus, and recombinant AAV vectors have proven to be highly efficient for gene delivery to a wide variety of cell types, tissue, and organs in small and large animal models.
• A number of AAVserotype vectorshavenow become available, with distinct tissue-tropism, and long-term transgene expression, and this repertoire is likely to expand.
• An ever increasing number of rationally designed and optimized novel AAV serotype vectors capable of targeting specific tissues and organs, is likely to further expand their therapeutic landscape.
• The safety of recombinant AAV vectors has been established in 162 Phase I/II/III clinical trials to date, and clinical efficacy has also been achieved in at least 6 human diseases.

In this review, a brief account of the historical perspective of the discovery of the first cellular receptor and co-receptor of the prototype adeno-associated virus serotype 2 (AAV2) will be presented. The Subsequent discovery of a number of AAV serotypes, and attempts to identify the cellular receptors and co-receptors for these serotype vectors has had significant implications in their use in human gene therapy. As additional AAV serotypes are discovered and isolated, a detailed understanding of their tropism is certainly likely to play a key role in all future studies, both basic science as well as clinical.