PMID- 37366284 OWN - NLM STAT- MEDLINE DCOM- 20230731 LR - 20230731 IS - 1097-0290 (Electronic) IS - 0006-3592 (Linking) VI - 120 IP - 8 DP - 2023 Aug TI - Controlled release of adeno-associated virus from alginate hydrogel microbeads with enhanced sensitivity to ultrasound. PG - 2371-2377 LID - 10.1002/bit.28482 [doi] AB - 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. CI - (c) 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC. FAU - Takatsuka, Shuhei AU - Takatsuka S AD - School of Integrated Design Engineering, Graduate School of Science and Technology, Keio University, Yokohama, Japan. FAU - Kubota, Takeshi AU - Kubota T AD - School of Integrated Design Engineering, Graduate School of Science and Technology, Keio University, Yokohama, Japan. FAU - Kurashina, Yuta AU - Kurashina Y AD - Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, Yokohama, Japan. AD - Division of Advanced Mechanical Systems Engineering, Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan. FAU - Kurihara, Sho AU - Kurihara S AD - Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan. AD - Division of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Hirabayashi, Motoki AU - Hirabayashi M AD - Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan. AD - Division of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Fujioka, Masato AU - Fujioka M AD - Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. AD - Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan. AD - Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan. FAU - Okano, Hirotaka James AU - Okano HJ AD - Division of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Onoe, Hiroaki AU - Onoe H AUID- ORCID: 0000-0003-0048-1580 AD - School of Integrated Design Engineering, Graduate School of Science and Technology, Keio University, Yokohama, Japan. AD - Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, Yokohama, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230627 PL - United States TA - Biotechnol Bioeng JT - Biotechnology and bioengineering JID - 7502021 RN - 0 (Hydrogels) RN - 0 (Alginates) RN - 0 (Delayed-Action Preparations) SB - IM MH - *Hydrogels MH - *Dependovirus/genetics MH - Alginates MH - Microspheres MH - Delayed-Action Preparations MH - Genetic Vectors OTO - NOTNLM OT - AAV OT - drug release OT - gene therapy OT - hydrogel microbeads OT - ultrasound EDAT- 2023/06/27 13:10 MHDA- 2023/07/31 06:42 CRDT- 2023/06/27 07:03 PHST- 2023/06/10 00:00 [revised] PHST- 2023/01/07 00:00 [received] PHST- 2023/06/14 00:00 [accepted] PHST- 2023/07/31 06:42 [medline] PHST- 2023/06/27 13:10 [pubmed] PHST- 2023/06/27 07:03 [entrez] AID - 10.1002/bit.28482 [doi] PST - ppublish SO - Biotechnol Bioeng. 2023 Aug;120(8):2371-2377. doi: 10.1002/bit.28482. Epub 2023 Jun 27.