Adeno-Associated Virus-Encapsulated Alginate Microspheres Loaded in Collagen Gel Carriers for Localized Gene Transfer

This work reports localized in vivo gene transfer by biodegradation of the adeno-associated virus-encapsulating alginate microspheres (AAV-AMs) loaded in collagen gel carriers. AAV-AMs are centrifugally synthesized by ejecting a mixed pre-gel solution of alginate and AAV to CaCl solution to form an...

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Bibliographic Details
Published in:Advanced healthcare materials 2024-05, Vol.13 (12), p.e2303546
Main Authors: Kurashina, Yuta, Kurihara, Sho, Kubota, Takeshi, Takatsuka, Shuhei, Hirabayashi, Motoki, Shimmura, Hajime, Miyahara, Hideo, Hioki, Aiki, Matsushita, Yutaka, Muramatsu, Jumpei, Ogawa, Yuki, Fujioka, Masato, Okano, Hirotaka J, Onoe, Hiroaki
Format: Article
Language:English
Subjects:
Alginates
Alginates - chemistry
Alginic acid
Animals
Biodegradation
Calcium chloride
Collagen
Collagen - chemistry
Cryopreservation
Dependovirus - genetics
Encapsulation
Gels - chemistry
Gene transfer
Gene Transfer Techniques
Glucuronic Acid - chemistry
Hexuronic Acids - chemistry
Humans
Hydrogels
Hydrogels - chemistry
Mice
Microspheres
Muscles
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Summary:This work reports localized in vivo gene transfer by biodegradation of the adeno-associated virus-encapsulating alginate microspheres (AAV-AMs) loaded in collagen gel carriers. AAV-AMs are centrifugally synthesized by ejecting a mixed pre-gel solution of alginate and AAV to CaCl solution to form an ionically cross-linked hydrogel microsphere immediately. The AAV-AMs are able to preserve the AAV without diffusing out even after spreading them on the cells, and the AAV is released and transfected by the degradation of the alginate microsphere. In addition, AAV-AMs can be stored by cryopreservation until use. By implanting this highly convenient AAV-encapsulated hydrogel, AAV-AMs can be loaded into collagen gel carriers to fix the position of the implanted AAV-AMs and achieve localized gene transfer in vivo. In vivo experiments show that the AAV-AMs loaded in collagen gel carriers are demonstrated to release the encapsulated AAV for gene transfer in the buttocks muscles of mice. While conventional injections caused gene transfer to the entire surrounding tissue, the biodegradation of AAV-AMs shows that gene transfer is achieved locally to the muscles. This means that the proposed AAV-loaded system is shown to be a superior method for selective gene transfer.
ISSN:2192-2640
2192-2659
2192-2659
DOI:10.1002/adhm.202303546