CAG-ChIEF-tdTOMATO AAV (Serotype 8)

Axonal transport is an important physiological process involving the transfer of materials between the cell body and the axon terminal of a neuron. Substances delivered to the axon are transported in the anterograde direction toward the axon terminal. Materials returned to the cell body are transported in the reverse direction. The phenomenon of retrograde transport in neurons underlies the delivery of therapeutic molecules via viral vectors. Adeno-associated virus (AAV) vectors are a diverse group of gene therapy tools that have demonstrated significant safety and transduction efficacy in multiple species. They are the most commonly used gene therapy vectors in the central nervous system (CNS) because they are nonpathogenic and can transduce dividing and quiescent cells in vivo. Important features of AAV viral vectors are their negligible immunogenicity and lack of cytotoxicity.

Expression of AAV-based therapeutic genes and molecules can persist for months in some cells. The most studied AAV vector serotypes are 1, 2, 5, 8, 9, recombinant human (rh)10, and PHP.eB, which also exhibit the capacity for anterograde and retrograde transport along neuronal processes. Retrograde transport of AAV vectors is an interesting phenomenon due to the large number of axonal projections present in the nervous system. Precise vector delivery to axon terminals allows their transport within adjacent brain structures and over long distances. The retrograde properties of AAV8 in the central nervous system have been described in several studies.