Adeno-associated virus serotype tropism and transduction in murine dorsal root ganglia following direct injection.

The peripheral nervous system (PNS) is highly heterogeneous, comprised of diverse subclasses of motor and sensory neurons. Optogenetics offers a high-resolution approach for interrogating neural circuits; however, optogenetic proteins must be selectively delivered to defined neuronal circuits in order to elucidate circuit-specific functional mechanisms. Adeno-associated viral vectors (AAVs) are widely used to deliver transgenes to the nervous system due to their relative safety and strong transgene expression. Multiple AAV serotypes are in common use, each capable of preferentially transducing distinct tissues and neuronal populations. However, characterization of the transduction behavior of these serotypes in the PNS, particularly in the dorsal root ganglia (DRG) and sensory nervous system (SNS), remain limited. This study evaluated the transduction efficiency of AAV8, AAV9, AAV2re, and PHP.S following direct intraganglionic injection into the DRG. AAV8, AAV9, and PHP.S exhibited comparable transduction efficiencies, whereas AAV2re transduced more than twofold fewer neurons. Despite similar overall efficiencies between AAV8, AAV9, and PHP.S, the neuronal volume distributions of transduced neurons were serotype-dependent. These results demonstrate that AAV serotype selection influences both the extent and size of transduced DRG neurons, indicating that serotype selection should be considered carefully when designing experiments that target peripheral sensory circuits.