Gene therapy in the inner ear using adenovirus vectors

Adv Otorhinolaryngol. 2009:66:37-51. doi: 10.1159/000218206. Epub 2009 Jun 2.

Abstract

Therapies for the protection and regeneration of auditory hair cells are of great interest given the significant monetary and lifestyle impact of hearing loss. The past decade has seen tremendous advances in the use of adenoviral vectors to achieve these aims. Preliminary data demonstrated the functional capacity of this technique as adenoviral-induced expression of neurotrophic and growth factors protected hair cells and spiral ganglion neurons from ototoxic insults. Subsequent efforts confirmed the feasibility of adenoviral transfection of cells in the auditory neuroepithelium via cochleostomy into the scala media. Most recently, efforts have focused on regeneration of depleted hair cells. Mammalian hearing loss is generally considered a permanent insult as the auditory epithelium lacks a basal layer capable of producing new hair cells. Recently, the transcription factor Atoh1 has been found to play a critical role in hair cell differentiation. Adenoviral-mediated overexpression of Atoh1 in culture and in vivo have shown the ability to regenerate auditory and vestibular hair cells by causing transdifferentiation of neighboring epithelial-supporting cells. Functional recovery of both the auditory and vestibular systems has been documented following adenoviral induced Atoh1 overexpression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenoviridae / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / physiology
  • Deafness / therapy
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors / therapeutic use*
  • Hair Cells, Vestibular / pathology
  • Hair Cells, Vestibular / physiology
  • Humans
  • Nerve Degeneration / prevention & control
  • Regeneration
  • Spiral Ganglion / physiology
  • Transduction, Genetic
  • Transfection

Substances

  • ATOH1 protein, human
  • Basic Helix-Loop-Helix Transcription Factors