Current issues in cochlear gene transfer.

Abstract

Cochlear gene therapy represents a potential experimental and therapeutic tool to understand and treat deafness. In designing cochlear gene transfer studies, the chosen route of delivery of vector and the choice of gene therapy vector have to be given careful consideration. Several different routes of delivery have been tested in our laboratory including infusion with osmotic minipump, direct microinjection into the cochlea and application of vector-transgene complex-soaked Gelfoam((R)) into the direct contact with the round window membrane. In our experience, the latter is an easy, safe and atraumatic technique to deliver gene into the cochlea. A number of different gene transfer vectors have been investigated in vivo for their efficacy, utility and safety in intracochlear gene transfer. Vectors successfully studied include cationic liposomes, adeno-associated virus, adenovirus, lentivirus, herpes simplex virus and vaccinia virus. While the viral vectors offer clear experimental advantages, human gene therapy in the future will likely utilize nonviral vectors to maximize safety. Finally, safety issues regarding dissemination of gene transfer vectors beyond the target cochlea will need to be adequately addressed.