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

Min A. Kim, Nari Ryu, Hye Min Kim, Ye Ri Kim, Byeonghyeon Lee, Tae Jun Kwon, Jinwoong Bok, Un Kyung Kim

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish
Pages (from-to)197-204
Number of pages8
JournalMolecular Therapy Methods and Clinical Development
Volume13
DOIs
StatePublished - 14 Jun 2019

Keywords

  • adeno-associated virus
  • gene therapy
  • genetic hearing loss
  • inner ear
  • serotype

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