AAV8-CAG-Cre-2A-GFP

Adeno-associated virus (AAV) vectors are the most commonly used viral vectors in current gene therapy applications. They combine several advantageous features, including a favorable safety profile, long-term stable gene expression in a variety of tissues, the ability to transduce both dividing and non-dividing cells, and physicochemical stability. AAV vectors generally exhibit low innate immunity, as well as low efficiency in transducing professional antigen-presenting cells, although recent studies warrant a more differentiated view of the immune response to AAV-mediated gene transfer. In clinical trials, humoral immune responses were generated, and memory CD8+ T cell responses were also observed. To circumvent these issues, a number of different AAV capsid variants have been isolated from non-human primates that exhibit enhanced transduction to certain tissues and may reduce seroprevalence and attenuate pre-existing capsid immune responses. In addition, different types of capsid modifications have been explored to improve tissue targeting and transduction efficiency.

Among the AAV serotypes identified to date, AAV type 8 (AAV8) vectors exhibit prominent liver tropism in mice compared to the most extensively studied serotype, AAV2. This trend also holds in skeletal muscle, cardiac tissue, pancreas, and glioblastoma, and specialized cells in the brain and retina are preferentially transduced by AAV8. In many animal models, AAV8 has been shown to have tremendous therapeutic potential, although translating the superior properties of AAV8 to higher primates has been challenging. The use of AAV8 vectors in clinical trials recently provided a successful proof of concept for expressing the factor IX gene in human liver.