Targeted Gene Delivery into the Mammalian Inner Ear Using Synthetic Serotypes of Adeno-Associated Virus Vectors

Molecular Therapy. Methods & Clinical Development
Min-A KimUn-Kyung Kim

Abstract

Targeting specific cell types in the mammalian inner ear is important for treating genetic hearing loss due to the different cell type-specific functions. Adeno-associated virus (AAV) is an efficient in vivo gene transfer vector, and it has demonstrated promise for treating genetic hearing loss. Although more than 100 AAV serotypes have been identified, few studies have investigated whether AAV can be distributed to specific inner ear cell types. Here we screened three EGFP-AAV reporter constructs (serotypes DJ, DJ8, and PHP.B) in the neonatal mammalian inner ear by injection via the round window membrane to determine the cellular specificity of the AAV vectors. Sensory hair cells, supporting cells, cells in Reissner's membrane, interdental cells, and root cells were successfully transduced. Hair cells in the cochlear sensory epithelial region were the most frequently transduced cell type by all tested AAV serotypes. The recombinant DJ serotype most effectively transduced a range of cell types at a high rate. Our findings provide a basis for improving treatment of hereditary hearing loss using targeted AAV-mediated gene therapy.

Citations

Jun 23, 2019·Human Molecular Genetics·Ryotaro OmichiRichard J H Smith
Jan 30, 2020·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Thomas R Van De Water
Dec 5, 2019·The Journal of the Acoustical Society of America·Jane A BurtonRamnarayan Ramachandran
May 11, 2020·Advanced Drug Delivery Reviews·Ning DingXue Gao
Aug 11, 2020·Molecular Therapy. Methods & Clinical Development·Chin-Ju HuYen-Fu Cheng
Feb 20, 2021·Hearing, Balance and Communication·Chris ValentiniAnil K Lalwani
Apr 18, 2021·Trends in Pharmacological Sciences·Cole W PetersKillian S Hanlon

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Methods Mentioned

BETA
cochlear gene therapy

Software Mentioned

GraphPad
Prism

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