Distributional comparison of different AAV vectors after unilateral cochlear administration.
Shuang HanZhijiao XuShengyi WangHonghai TangShaowei HuHui WangGuo-Fang GuanYi-Lai ShuPublished in: Gene therapy (2023)
The adeno-associated virus (AAV) gene therapy has been widely applied to mouse models for deafness. But, AAVs could transduce non-targeted organs after inner ear delivery due to their low cell-type specificity. This study compares transgene expression and biodistribution of AAV1, AAV2, Anc80L65, AAV9, AAV-PHP.B, and AAV-PHP.eB after round window membrane (RWM) injection in neonatal mice. The highest virus concentration was detected in the injected cochlea. AAV2, Anc80L65, AAV9, AAV-PHP.B, and AAV-PHP.eB transduced both inner hair cells (IHCs) and outer hair cells (OHCs) with high efficiency, while AAV1 transduced IHCs with high efficiency but OHCs with low efficiency. All AAV subtypes finitely transduced contralateral inner ear, brain, heart, and liver compared with the injected cochlea. In most brain regions, the enhanced green fluorescent protein (eGFP) expression of AAV1 and AAV2 was lower than that of other four subtypes. We suggested the cochlear aqueduct might be one of routes for vectors instantaneously infiltrating into the brain from the cochlea through a dye tracking test. In summary, our results provide available data for further investigating the biodistribution of vectors through local inner ear injection and afford a reference for selecting AAV serotypes for gene therapy toward deafness.
Keyphrases
- gene therapy
- high efficiency
- induced apoptosis
- poor prognosis
- metabolic syndrome
- resting state
- adipose tissue
- cell proliferation
- computed tomography
- brain injury
- machine learning
- signaling pathway
- electronic health record
- multiple sclerosis
- cerebral ischemia
- cancer therapy
- subarachnoid hemorrhage
- high fat diet induced