ArticleBioengineering & translational medicine2021
Ultrasound-microbubble cavitation facilitates adeno-associated virus mediated cochlear gene transfection across the round-window membrane.
Article in Bioengineering & translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 18 citations in OpenAlex.
- The role of the y(+)L-type amino acid transporter 2 in promoting zinc absorption as zinc proteinate with moderate chelation strength in broiler primary duodenal epithelial cells.Journal of animal science · 2026Article
- Biomaterial-based gene therapy.MedComm · 2023Review
- Towards the Clinical Application of Gene Therapy for Genetic Inner Ear Diseases.Journal of clinical medicine · 2023Review
- Ultrasound-microbubble cavitation facilitates adeno-associated virus mediated cochlear gene transfection across the round-window membrane.Bioengineering & translational medicine · 2021Article
- Ultrasound Microbubble-Facilitated Inner Ear Delivery of Gold Nanoparticles Involves Transient Disruption of the Tight Junction Barrier in the Round Window Membrane.Frontiers in pharmacology · 2021Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The round window of the cochlea provides an ideal route for delivering medicines and gene therapy reagents that can cross the round window membrane (RWM) into the inner ear. Recombinant adeno-associated viruses (rAAVs) have several advantages and are recommended as viral vectors for gene transfection. However, rAAVs cannot cross an intact RWM. Consequently, ultrasound-mediated microbubble (USMB) cavitation is potentially useful, because it can sonoporate the cell membranes, and increase their permeability to large molecules. The use of USMB cavitation for drug delivery across the RWM has been tested in a few animal studies but has not been used in the context of AAV-mediated gene transfection. The currently available large size of the ultrasound probe appears to be a limiting factor in the application of this method to the RWM. In this study, we used home-made ultrasound probe with a decreased diameter to 1.5 mm, which enabled the easy positioning of the probe close to the RWM. In guinea pigs, we used this probe to determine that (1) USMB cavitation caused limited damage to the outer surface layer or the RWM, (2) an eGFP-gene carrying rAAV could effectively pass the USMB-treated RWM and reliably transfect cochlear cells, and (3) the hearing function of the cochlea remained unchanged. Our results suggest that USMB cavitation of the RWM is a good method for rAAV-mediated cochlear gene transfection with clear potential for clinical translation. We additionally discuss several advantages of the small probe size.
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