AbstractObjectivesThe goal of this project was to evaluate the use of two adeno‐associated viral vector serotypes, adeno‐associated viral vectors (AAV)‐2 and AAV‐6, approved for and used for gene therapy in humans, for the delivery of therapeutic genes to the temporomandibular joint (TMJ) and the attendant sensory nerves.MethodsYoung adult wild‐type C57BL/6 mice were intra‐articularly inoculated with AAV‐2 and AAV‐6 encoding the reporter gene gfp, the expression of which was assessed in the TMJ as well as along nerves innervating the TMJ.ResultsAAV‐2 and AAV‐6 serotypes were characterized by varying levels of tissue tropism demonstrating different efficacy of infection for articular chondrocytes, meniscal fibroblasts, and trigeminal neurons. Specifically, AAV‐2 infected both neurons and articular chondrocytes/meniscal fibroblasts, whereas AAV‐6 showed selectivity primarily for neurons.ConclusionsThe results of this study are clinically significant in the successful application of gene therapy vectors for TMJ disorders, as this new knowledge will allow for appropriate targeting of specific therapeutic genes to selective tissues (neurons vs. chondrocytes/fibroblasts) as needed by using specific viral vector serotypes.