Inner ear gene delivery: vectors and routes

Abstract

Objectives

Current treatments for hearing loss offer some functional improvements in hearing, but do not restore normal hearing. The aim of this review is to highlight recent advances in viral and non-viral vectors for gene therapy and to discuss approaches for overcoming barriers inherent to inner ear delivery of gene products.

Data Sources

The databases used were Medline, EMBASE, Web of Science, and Google Scholar. Search terms were [(‘cochlea*’ or ‘inner ear’ or ‘transtympanic’ or ‘intratympanic’ or ‘intracochlear’ or ‘hair cells’ or ‘spiral ganglia’ or ‘Organ of Corti’) and (‘gene therapy’ or ‘gene delivery’)]. The references section of resulting articles was also used to identify relevant studies.

Results

Both viral and non-viral vectors play important roles in advancing gene delivery to the inner ear. The round window membrane is one significant barrier to gene delivery that intratympanic delivery methods attempt to overcome through diffusion and intracochlear delivery methods bypass completely.

Conclusions

Gene therapy for hearing loss is a promising treatment for restoring hearing function by addressing innate defects. Recent technological advances in inner ear drug delivery techniques pose exciting opportunities for progress in gene therapy.

Keywords:

• Gene therapy
• hearing loss
• viral vector
• non-viral vector
• inner ear delivery

Disclosure statement

Dr. Anil K. Lalwani serves on the Medical Advisory Board for Advanced Bionics and on the Surgical Advisory Board for MED-EL. For the remaining authors, no conflicts of interest were declared.

Author contributions

CV, BS, and AKL designed research methods, performed literature search and review, wrote the paper and are responsible for final content. All authors read and approved the final manuscript.

Additional information

Funding

The authors gratefully acknowledge support by the National Institutes of Health (NIH) National Institute on Deafness and Other Communication Disorders (NIDCD) with award number R01DC014547.