AAV Null (Serotype Retrograde)

The ability of viral vectors to transport retrogradely axons enables the viral payload to enter projection neurons, meaning that even if the virus is spatially far from the cell body, it can still infect neurons as long as it is exposed at the axon terminal. Such viral vectors can be used to map and analyze projection neuron circuits, and can also be used to modify projection neurons. Many naturally evolved viruses can be transmitted retrogradely, including rabies virus, human immunodeficiency virus, herpes simplex virus, varicella-zoster virus, West Nile virus, and poliovirus. Rabies virus, human immunodeficiency virus, and herpes simplex virus have been used as viral vectors. The use of rabies virus in gene therapy has been hampered by its excessive toxicity, but progress has been made in reducing its toxicity. In addition to naturally evolved viruses, other viruses can also infect projection neurons, among which lentivirus, adenovirus, and adeno-associated virus (AAV) are widely used in research, especially in the field of gene therapy. Recombinant adeno-associated virus is a powerful gene delivery vector. Compared with wild-type AAV, recombinant AAV does not have rep or cap genes, but carries exogenous genes, which makes recombinant AAV useful for gene therapy. AAV has the following advantages: ① Low toxicity. Many clinical trials have shown that AAV has no persistent or late toxicity, such as clinical trials in patients with hemophilia B; ② Small immune response; ③ Mild inflammatory response; ④ AAV-delivered transgenes can be expressed for a long time. In 2016, a designed AAV variant was shown to efficiently retrogradely infect projection neurons. Over the past 20 years, a lot of research has been done on the application of AAV's retrograde axonal transport ability, and people have begun to use retrograde AAV to treat diseases.