AAV PHP.S-Null

Adeno-associated virus (AAV) has become one of the tools of choice for neuroscience research. Due to its ease of use and efficient delivery of various gene products, including fluorescent proteins, AAV has greatly facilitated the mapping and manipulation of brain neural circuits. Depending on the serotype, AAV is effective in different brain regions, has specific uptake into neuronal and/or glial cell populations, and selectively transports anterogradely or retrogradely in CNS neurons. Stereotaxic injection at the target site, combined with the use of virally delivered or transgenic expressed Cre and Flp recombinases, allows the construction of detailed maps of the projections of selected neuronal populations and their functional interactions. Many studies have reported AAV-mediated transduction of peripheral neurons using various delivery methods such as sciatic nerve injection, direct intraganglionic injection, and intrathecal infusion. However, these methods are invasive and inefficient, and the viral particles lack broad tropism for peripheral neurons. Another approach to preferentially transduce peripheral sensory neurons is to inject the virus into the blood circulation, taking advantage of the difficulty of AAV to cross the blood-brain barrier. This approach alone does not completely restrict transduction to peripheral neurons. Significant progress has been made in the development of a synthetic neurotropic serotype, AAV.PHP.S, which was generated by directed evolution. A variant of the Cap gene of AAV9 was introduced and then subjected to repeated phenotypic selection to transdural sensory neurons of the dorsal root ganglion. When the resulting pseudotyped AAV-PHP.S particle is introduced into the blood circulation, it predominantly infects peripheral neurons or exclusively.