Inner-Ear Gene Therapy for Hereditary Hearing Loss: A PubMed-Based Scoping Review of Published Human Studies and the Clinical Trial Registry Landscape

Abstract

Gene therapy for hereditary hearing loss has entered early clinical translation, but human evidence remains limited. This scoping review mapped published human evidence and situated it within the broader clinical trial landscape. Following PRISMA-ScR, PubMed was searched on April 17, 2026, for peer-reviewed human studies of therapeutic gene transfer for hereditary hearing loss published from 2015 to 2026. Restriction to one bibliographic database is acknowledged, and the review is framed as a PubMed-based scoping review rather than a comprehensive multi-database synthesis. ClinicalTrials.gov, ICTRP, ChiCTR, and CTIS were also searched. Records were manually screened and deduplicated across registries. A primary reviewer screened titles and abstracts, and a second reviewer verified all full-text and registry inclusion decisions. PubMed yielded 129 records, of which six studies from three independent clinical programs were included. All targeted OTOF-related deafness using intracochlear dual-vector AAV systems. Three publications represented 11 unique participants from ChiCTR2200063181; two Otovia publications (NCT05901480) reported overlapping cohorts; and one publication reported the DB-OTO trial (NCT05788536). Overall, the evidence represented approximately 33 unique participants, not the publication-level total of 46. Auditory outcomes generally improved, but reporting was heterogeneous and follow-up was short. Registry searches yielded 632 raw records and nine unique interventional trials after screening and deduplication. Eight targeted OTOF, one targeted GJB2, and none targeted TMC1. Published evidence remains confined to early-phase studies of a single genetic subtype, whereas registry data indicate a broader, evolving landscape. Generalizability, target imbalance, and long-term safety remain unresolved.