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Intravenous rAAV2/9 injection for murine cochlear gene delivery
Seiji B Shibata1,2, Hidekane Yoshimura2,3, Paul T Ranum2,4
1Department of Otolaryngology - Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Scientific Reports
|August 31, 2017
Summary
Systemic gene therapy using adeno-associated virus serotype 9 (AAV9) enables non-invasive delivery to the cochlea in neonatal mice. This approach successfully transduced inner hair cells and spiral ganglion neurons without affecting hearing acuity.
Area of Science:
- Otolaryngology
- Gene Therapy
- Neuroscience
Background:
- Genetic deafness presents a significant challenge, driving research into gene therapy for hearing restoration.
- Direct gene delivery to the inner ear faces physiological barriers, limiting systemic approaches.
Purpose of the Study:
- To investigate the efficacy of systemic delivery of adeno-associated virus serotype 9 (AAV2/9) for cochlear transduction.
- To characterize the non-invasive potential of intravenous gene delivery to the inner ear.
Main Methods:
- Intravenous injection of AAV2/9 carrying an eGFP reporter gene into wild-type neonatal mice.
- Analysis of cochlear transduction in inner hair cells, spiral ganglion neurons, and vestibular hair cells.
- Assessment of hearing acuity and influence of viral serotype and age on transduction efficiency.
Main Results:
- Systemic AAV2/9 injection resulted in binaural transduction of key inner ear cell types.
- Transduction efficiency demonstrated a dose-dependent relationship and an apex-to-base gradient in inner hair cells.
- No significant changes in hearing acuity were observed at postnatal day 30.
Conclusions:
- Intravenous AAV2/9 delivery is a viable, atraumatic method for cochlear gene transfer in early postnatal mice.
- Transduction efficiency is influenced by viral serotype and the age of the animal at the time of injection.
