AAV9-CMV-Cas9

Over the past decade, adeno-associated virus (AAV) vectors have emerged as the most promising gene delivery system for human gene therapy. Recombinant AAV vectors can transduce a variety of tissues in vivo and achieve long-term gene expression without eliciting a significant cell-mediated immune response. To date, 4100 AAV serotypes have been reported. AAV serotype 9 (AAV-9) is a particularly attractive vector due to its excellent performance in skeletal muscle, heart, and lungs. In order to reach every tissue/organ of the body, gene therapy vectors can be introduced into the bloodstream via the venous or arterial circulation. Theoretically, one can speculate on the advantages/limitations of each delivery option based on anatomy. For example, after intravenous (i.v.) injection, returning blood will first carry AAV to the right ventricle and lungs. In contrast, after intra-arterial injection, AAV reaches muscles and all other tissues first, and finally the lungs. Spatial and temporal differences between these pathways may alter the transduction properties of different tissues and/or organs. Comparison of recently discovered serotypes shows that AAV-9 transduces to the heart, lungs, and tibialis anterior (TA) muscles after intravenous (IV) injection better than all other serotypes and is independent of age, whereas transduction to the liver and kidneys are related to age.