AAV8-CMV-FLuc

Adeno-associated viral vectors (AAV) have now become one of the standard tools for delivering genes into the central nervous system. For example, transduction of neurons with optogenetic molecules provides unprecedented opportunities for manipulating neural circuits. To generate recombinant AAV particles, the transcription unit of interest is sandwiched between two inverted terminal repeats (ITRs) of AAV and packaged with a capsid provided in trans. A characteristic of AAV is the existence of a large number of different serotypes that exhibit unique species and tissue tropisms. Capsids derived from these serotypes can be used to package transfer vectors of AAV2 to confer unique transduction properties and cell tropisms.

To a large extent, the safety of the vector is influenced by the distribution of AAV in vivo. A large body of experimental data shows that recombinant AAV (rAAV) can be detected in the circulation system and, in addition, can infect multiple cells in specific tissues depending on the route of administration of the vector. After intraretinal or intravitreal injection into the choroid of primates, the presence of the rAAV8 vector was detected in the atrial fluid, anterior chamber, and blood. Quantitative PCR was used to detect vectors in peripheral organs, and rAAV8 was found in the spleen and liver, with lower copy numbers in lymphoid organs. Lieshout et al. reported that AAV8 vectors were detected in all major tissues and blood 2 weeks after tail vein injection in mice, with the highest levels in the liver and the lowest levels in the brain. In addition, 3 months after intramuscular injection of vectors in rhesus monkeys, expression was detected in both muscle and liver, although the levels in the liver were higher and positively correlated with vector concentration. In summary, these findings reflect the hepatotropic properties of AAV8.