AAV gene therapy vectors in the TMJ

Sabine M. Brouxhon, Michael Kerry O'Banion, Stephanos Kyrkanides

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: The 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. Methods: Young 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. Results: AAV-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. Conclusions: The 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.

Original languageEnglish
JournalClinical and Experimental Dental Research
DOIs
StateAccepted/In press - 2022

Bibliographical note

Funding Information:
We would like to thank Dr. Ross H. Tallents and Ms. Jen‐nie H. Miller for their assistance in animal care, injection of the viral vectors, animal euthanasia, and tissue processing. We would also like to express our gratitude to Dr. Brandon Harvey, Chief, Molecular Mechanisms of Cellular Stress and Inflammation, and Director of the Transgenic Rat Project, who packaged the AAV vectors at the National Institute for Drug Abuse/National Institute of Health. This study was funded in part by NIH grants AR055035 and DE017765 to S. K., as well as start‐up funding provided to S. K. from the Eastman Dental Foundation through the University of Rochester Eastman Institute for Oral Health.

Publisher Copyright:
© 2022 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

Keywords

  • gene therapy
  • TMJ
  • trigeminal nerve
  • vectors

ASJC Scopus subject areas

  • Dentistry (all)

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