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Life sciences · Journal article
Ear and Hearing · October 13, 2026
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Abstract: Gene delivery and the various routes of administration used to deliver viral vectors constitute a rapidly evolving field, with recent success in restoring hearing in children with OTOF variants in ongoing clinical otoferlin trials. With the rise of gene therapy for major hereditary hearing disorders, both syndromic and nonsyndromic, there has been parallel progress in the development of new delivery methods. Advances in intratympanic injection of antibiotics and corticosteroids, along with nearly half a century of experience in cochlear implantation surgery, have enabled multiple local and systemic approaches to access the inner ear. Recent industry investment in gene therapy and delivery technologies has accelerated scientific progress, underscoring the need for continuous evaluation of the most suitable gene delivery strategies for different causes of hearing loss. Although most gene delivery in animal models has been performed via round window membrane injection, yielding promising results in cochlear hair cell transduction, potential drawbacks remain for clinical translation—particularly limited vector distribution, which may result in a basal-to-apical gradient. Venting procedures such as stapes footplate fenestration or canalostomy have been explored to mitigate these limitations, and recent intrathecal or even in utero injections have been investigated as alternative approaches. Hearing loss can be inherited in multiple ways, and patient treatment with gene delivery, or even the type of gene therapy itself, may vary with the recent success of CRISPR/Cas-based editing tools. Understanding the genetic etiology of inner ear disorders has facilitated the identification of therapeutic targets and innovative delivery approaches. This review summarizes the current understanding of delivery routes for gene therapy, highlighting their respective strengths and limitations as demonstrated in translational and clinical research to date. Furthermore, it examines advances in drug delivery and clinical applications in the context of emerging therapeutics, providing an integrated overview and perspective on the future direction of gene delivery strategies.