RT Journal Article
SR Electronic
T1 Close-Field Electroporation Gene Delivery Using the Cochlear Implant Electrode Array Enhances the Bionic Ear
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 233ra54
OP 233ra54
DO 10.1126/scitranslmed.3008177
VO 6
IS 233
A1 Pinyon, Jeremy L.
A1 Tadros, Sherif F.
A1 Froud, Kristina E.
A1 Y. Wong, Ann C.
A1 Tompson, Isabella T.
A1 Crawford, Edward N.
A1 Ko, Myungseo
A1 Morris, Renée
A1 Klugmann, Matthias
A1 Housley, Gary D.
YR 2014
UL http://stm.sciencemag.org/content/6/233/233ra54.abstract
AB The cochlear implant is the most successful bionic prosthesis and has transformed the lives of people with profound hearing loss. However, the performance of the “bionic ear” is still largely constrained by the neural interface itself. Current spread inherent to broad monopolar stimulation of the spiral ganglion neuron somata obviates the intrinsic tonotopic mapping of the cochlear nerve. We show in the guinea pig that neurotrophin gene therapy integrated into the cochlear implant improves its performance by stimulating spiral ganglion neurite regeneration. We used the cochlear implant electrode array for novel “close-field” electroporation to transduce mesenchymal cells lining the cochlear perilymphatic canals with a naked complementary DNA gene construct driving expression of brain-derived neurotrophic factor (BDNF) and a green fluorescent protein (GFP) reporter. The focusing of electric fields by particular cochlear implant electrode configurations led to surprisingly efficient gene delivery to adjacent mesenchymal cells. The resulting BDNF expression stimulated regeneration of spiral ganglion neurites, which had atrophied 2 weeks after ototoxic treatment, in a bilateral sensorineural deafness model. In this model, delivery of a control GFP-only vector failed to restore neuron structure, with atrophied neurons indistinguishable from unimplanted cochleae. With BDNF therapy, the regenerated spiral ganglion neurites extended close to the cochlear implant electrodes, with localized ectopic branching. This neural remodeling enabled bipolar stimulation via the cochlear implant array, with low stimulus thresholds and expanded dynamic range of the cochlear nerve, determined via electrically evoked auditory brainstem responses. This development may broadly improve neural interfaces and extend molecular medicine applications.