Gene transfer in human vestibular epithelia and the prospects for inner ear gene therapy

Laryngoscope. 2008 May;118(5):821-31. doi: 10.1097/MLG.0b013e318164d0aa.


Transfer of exogenous genetic material into the mammalian inner ear using viral vectors has been characterized over the last decade. A number of different viral vectors have been shown to transfect the varying cell types of the nonprimate mammalian inner ear. Several routes of delivery have been identified for introduction of vectors into the inner ear while minimizing injury to existing structures and at the same time ensuring widespread distribution of the agent throughout the cochlea and the rest of the inner ear. These studies raise the possibility that gene transfer may be developed as a potential strategy for treating inner ear dysfunction in humans. Furthermore, a recent report showing successful transfection of excised human vestibular epithelia offers proof of principle that viral gene transfer is a viable strategy for introduction and expression of exogenous genetic material to restore function to the inner ear. Human vestibular epithelia were harvested from patients undergoing labyrinthectomy, either for intractable Ménière's disease or vestibular schwannoma resection, and cultured for as long as 5 days. In those experiments, recombinant, multiply-deleted, replication-deficient adenoviral vectors were used to transfect and express a reporter gene as well as the functionally relevant gene, wild-type KCNQ4, a potassium channel gene that when mutated causes the autosomal dominant HL DFNA2.Here, we review the current state of viral-mediated gene transfer in the inner ear and discuss different viral vectors, routes of delivery, and potential applications of gene therapy. Emphasis is placed on experiments demonstrating viral transfection of human inner ear tissue and implications of these findings and for the future of gene therapy in the human inner ear.

MeSH terms

  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Ear Diseases / pathology*
  • Ear Diseases / therapy*
  • Ear, Inner / pathology*
  • Epithelium / pathology*
  • Feasibility Studies
  • Gene Transfer Techniques / instrumentation*
  • Genes, Viral / genetics*
  • Genetic Vectors / therapeutic use
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Hair Cells, Auditory, Inner / metabolism
  • Hair Cells, Auditory, Outer / metabolism
  • Hearing Loss, Sensorineural / genetics
  • Hearing Loss, Sensorineural / therapy
  • Humans
  • KCNQ Potassium Channels / genetics
  • Meniere Disease / therapy
  • Neuroma, Acoustic / therapy
  • Regeneration / physiology
  • Tissue and Organ Harvesting
  • Transfection
  • Vestibule, Labyrinth / pathology*


  • Brain-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor
  • KCNQ Potassium Channels
  • KCNQ4 protein, human