Advancements and future prospects of adeno-associated virus-mediated gene therapy for sensorineural hearing loss

Sensorineural hearing loss (SNHL), a highly prevalent sensory impairment, results from a multifaceted interaction of genetic and environmental factors. As we continually gain insights into the molecular basis of auditory development and the growing compendium of deafness genes identified, research o...

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Published inFrontiers in neuroscience Vol. 18; p. 1272786
Main Authors Li, Linke, Shen, Tian, Liu, Shixi, Qi, Jieyu, Zhao, Yu
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 24.01.2024
Frontiers Media S.A
Subjects
adeno-associated virus
Adenoviruses
Animal models
Cells
Clinical trials
Cochlear implants
Deafness
delivery route
dual-AAV
Efficiency
Environmental factors
Fetuses
Gene silencing
Gene therapy
Genomes
Hair
Hearing aids
Hearing loss
Hearing protection
Herpes viruses
Inner ear
Neuroscience
Ototoxicity
Plasmids
Proteins
sensorineural hearing loss
Signal transduction
Transgenes
Vectors (Biology)
sensorineural hearing loss
dual-AAV
gene therapy
adeno-associated virus
delivery route
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Summary:Sensorineural hearing loss (SNHL), a highly prevalent sensory impairment, results from a multifaceted interaction of genetic and environmental factors. As we continually gain insights into the molecular basis of auditory development and the growing compendium of deafness genes identified, research on gene therapy for SNHL has significantly deepened. Adeno-associated virus (AAV), considered a relatively secure vector for gene therapy in clinical trials, can deliver various transgenes based on gene therapy strategies such as gene replacement, gene silencing, gene editing, or gene addition to alleviate diverse types of SNHL. This review delved into the preclinical advances in AAV-based gene therapy for SNHL, spanning hereditary and acquired types. Particular focus is placed on the dual-AAV construction method and its application, the vector delivery route of mouse inner ear models (local, systemic, fetal, and cerebrospinal fluid administration), and the significant considerations in transforming from AAV-based animal model inner ear gene therapy to clinical implementation.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ObjectType-Review-1
Lukas D. Landegger, Medical University of Vienna, Austria
Reviewed by: Zheng-Yi Chen, Massachusetts Eye & Ear Infirmary and Harvard Medical School, United States
Edited by: Hinrich Staecker, University of Kansas Medical Center, United States
These authors have contributed equally to this work and share first authorship
ISSN:1662-4548
1662-453X
1662-453X
DOI:10.3389/fnins.2024.1272786