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Controlled release of adeno-associated virus from alginate hydrogel microbeads with enhanced sensitivity to ultrasound |
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| Authors: | Shuhei Takatsuka Takeshi Kubota Yuta Kurashina Sho Kurihara Motoki Hirabayashi Masato Fujioka Hirotaka James Okano Hiroaki Onoe |
| Affiliation: | 1. School of Integrated Design Engineering, Graduate School of Science and Technology, Keio University, Yokohama, Japan;2. Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, Yokohama, Japan Division of Advanced Mechanical Systems Engineering, Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan;3. Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan Division of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan;4. Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan;5. Division of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan |
| Abstract: | Adeno-associated virus (AAV)-based gene therapy holds promise as a fundamental treatment for genetic disorders. For clinical applications, it is necessary to control AAV release timing to avoid an immune response to AAV. Here we propose an ultrasound (US)-triggered on-demand AAV release system using alginate hydrogel microbeads (AHMs) with a release enhancer. By using a centrifuge-based microdroplet shooting device, the AHMs encapsulating AAV with tungsten microparticles (W-MPs) are fabricated. Since W-MPs work as release enhancers, the AHMs have high sensitivity to the US with localized variation in acoustic impedance for improving the release of AAV. Furthermore, AHMs were coated with poly-l -lysine (PLL) to adjust the release of AAV. By applying US to the AAV encapsulating AHMs with W-MPs, the AAV was released on demand, and gene transfection to cells by AAV was confirmed without loss of AAV activity. This proposed US-triggered AAV release system expands methodological possibilities in gene therapy. |
| Keywords: | AAV drug release gene therapy hydrogel microbeads ultrasound |