|Title||Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Andres-Mateos E, Landegger LD, Unzu C, Phillips J, Lin BM, Dewyer NA, Sanmiguel J, Nicolaou F, Valero MD, Bourdeu KI, Sewell WF, Beiler RJ, McKenna MJ, Stankovic KM, Vandenberghe LH|
|Date Published||2022 03 15|
|Keywords||Animals, Cochlea, Dependovirus, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors, Macaca mulatta, Mice|
Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model. Five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane after making a small fenestra in the oval window. The procedure was well tolerated. All but one animal showed cochlear eGFP expression 7-14 days following injection. Anc80L65 in 2 animals transduced up to 90% of apical inner hair cells; AAV1 was markedly less efficient at equal dose. Transduction for both vectors declined from apex to base. These data motivate future translational studies to evaluate gene therapy for human hearing disorders.
|Alternate Journal||Nat Commun|
|PubMed Central ID||PMC8924271|
|Grant List||R01 DC015824 / DC / NIDCD NIH HHS / United States|
Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate.
Nicholas Dewyer, MD