Novel strategy to target glioblastoma-initiating cells using a braintropic adeno-associated virus carrying a miR-dependent genome-editing system

Wang, Zhe; Zou, Peilin; Chen, Zhenzhong; Hou, Jiahui; Son, You Lee; Yamashita, Daisuke; Kondo, Toru

Novel strategy to target glioblastoma-initiating cells using a braintropic adeno-associated virus carrying a miR-dependent genome-editing system

Wang, Zhe; Zou, Peilin; Chen, Zhenzhong et al.

British journal of cancer, 2025, 132, 1100-1109

Permalink : https://hdl.handle.net/2115/96171

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/96171
タイトル	Novel strategy to target glioblastoma-initiating cells using a braintropic adeno-associated virus carrying a miR-dependent genome-editing system
著者	Wang, Zhe ; Zou, Peilin ; Chen, Zhenzhong ; Hou, Jiahui ; Son, You Lee ; Yamashita, Daisuke ; Kondo, Toru
著者名 Wang, Zhe
著者名 Zou, Peilin
著者名 Chen, Zhenzhong
著者名 Hou, Jiahui
e-Rad_Researcher 10605306 著者名 Son, You Lee
著者名 Yamashita, Daisuke
e-Rad_Researcher 30270573 著者名 Kondo, Toru
言語	英語
キーワード	Glioblastoma-initiating cell (GIC)
	MicroRNA
	Cas9
	DHODH
	Adeno-associated virus (AAV)
	Braintropic capsid
発行日	2025-04-12
出版者	Springer Nature
収録物名	British journal of cancer
巻(号)	132
ページ	1100-1109
抄録	Background Since glioblastoma (GBM)-initiating cells (GICs) were identified as the cells-of-origin for GBM, various GIC factors have been analyzed as potential therapeutic targets. However, these targets are also present in normal cells outside of the brain, raising concerns about potential side effects when directly targeted. The aim of this study is to develop a novel method that specifically eradicates GICs with reducing side effects. Methods We selected micoRNAs (miRs) that are significantly decreased in GICs compared to normal cells and developed a genome-editing (GE) system that knocks out a functional GIC factor in a miR-dependent manner (miR-dependent GE). Additionally, we developed mosaic-capsids that consist of braintropic and universal capsids, which deliver genes into GIC brain tumors. Results Systemic administration of the mosaic-capsids Adeno-associated virus (AAV) carrying a miR-dependent GFP expression cassette selectively expressed GFP in GICs transplanted into the brains of immunodeficient mice, without expression in either mouse brain cells or non-brain tissues. The mosaic-capsids AAV carrying a miR-dependent GE prevented GIC tumorigenesis in the brain and extended the survival time of tumor-bearing mice. Conclusion These data indicate that the mosaic-capsids AAV containing a miR-dependent GE represents a novel therapeutic virus for GBM with fewer side effects.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1038/s41416-025-03007-3
PISSN	0007-0920
EISSN	1532-1827
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1038/s41416-025-03007-3