Enhanced Cochlear Transduction by AAV9 with High-Concentration Sucrose

Area of Science:

• Oto-genetics
• Gene Therapy Delivery
• Molecular Biology

Background:

• Sensorineural hearing loss (SNHL) involves inner ear damage, making it a target for gene therapy.
• Adeno-associated virus (AAV) vectors, particularly AAV9 variants, are used for inner ear gene transfer but require high doses.
• Efficient and safe gene delivery to inner ear cells is crucial for therapeutic success.

Purpose of the Study:

• To investigate the effect of sucrose on adeno-associated virus (AAV) vector-mediated gene transduction in the inner ear.
• To determine if sucrose enhances gene transfer to inner ear cells in vitro and in vivo.
• To assess the safety of sucrose co-administration on auditory function.

Main Methods:

• In vitro transduction assays using House Ear Institute-Organ of Corti 1 (HEI-OC1) cells with an AAV9 variant vector and varying sucrose concentrations.
• In vivo administration of an AAV9 variant vector with sucrose to mouse inner ears.
• Auditory brainstem response (ABR) testing to evaluate the effect of the procedure on hearing thresholds.

Main Results:

• High concentrations of sucrose significantly increased gene transduction in HEI-OC1 cells in vitro.
• Simultaneous administration of sucrose enhanced AAV9 variant vector transduction in mouse inner hair cells (IHCs) and spiral ligament cells.
• Sucrose co-administration did not adversely affect auditory function, as indicated by stable ABR thresholds.

Conclusions:

• Sucrose enhances the transduction efficiency of AAV9 variant vectors in the inner ear.
• This sucrose-mediated enhancement of gene delivery is safe for auditory function.
• This approach offers a promising strategy for developing gene therapies for adult-onset sensorineural hearing loss.