Mitochondrial transgene expression via an artificial mitochondrial DNA vector in cells from a patient with a mitochondrial disease

Ishikawa, Takuya; Somiya, Kana; Munechika, Reina; Harashima, Hideyoshi; Yamada, Yuma

Mitochondrial transgene expression via an artificial mitochondrial DNA vector in cells from a patient with a mitochondrial disease

Ishikawa, Takuya; Somiya, Kana; Munechika, Reina et al.

Journal of controlled release, 2018, 274, 109-117

Permalink : https://hdl.handle.net/2115/73334

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アクセス権	open access
URI	https://hdl.handle.net/2115/73334
タイトル	Mitochondrial transgene expression via an artificial mitochondrial DNA vector in cells from a patient with a mitochondrial disease
著者	Ishikawa, Takuya ; Somiya, Kana ; Munechika, Reina ; Harashima, Hideyoshi ; Yamada, Yuma
著者名 Ishikawa, Takuya
著者名 Somiya, Kana
著者名 Munechika, Reina
e-Rad_Researcher 00183567 著者名 Harashima, Hideyoshi
e-Rad_Researcher 60451431 著者名 Yamada, Yuma
言語	英語
キーワード	Mitochondria
	Transgene expression
	Independent clinical study
	Mitochondrial disease's patient
	Mitochondrial delivery
	MITO-Porter
発行日	2018-03-28
出版者	Elsevier
収録物名	Journal of controlled release
巻(号)	274
ページ	109-117
抄録	To achieve mitochondrial gene therapy, developing a mitochondrial transgene expression system that produces therapeutic proteins in mitochondria of disease cells is essential. We previously reported on the design of pCMV-mtLuc (CGG) containing a CMV promotor and a NanoLuc (Nluc) luciferase gene that records adjustments to the mitochondrial codon system, and showed that the mitochondrial transfection of pCMV-mtLuc (CGG) resulted in the efficient production of the Nluc luciferase protein in human HeLa cells. This mitochondrial transfection was achieved using a MITO-Porter, a liposome-based carrier for delivering a cargo to mitochondria via membrane fusion. We report herein that mitochondrial transfection using the MITO-Porter results in mitochondrial transgene expression in G625A fibroblasts obtained from a patient with a mitochondrial disease. We investigated the effect of promoters and the basic structure of pCMV-mtLuc (CGG) on gene expression efficiency, and were able to construct a high performance mitochondrial DNA vector, pCMV-mtLuc (CGG) [hND4] that contains a human mitochondrial endogenous gene. We also constructed an RP/KALA-MITO-Porter composed of the KALA peptide (cell-penetrating peptide) with a mitochondrial RNA aptamer to enhance cellular uptake and mitochondrial targeting. Finally, the mitochondrial transfection of pCMV-mtLuc (CGG) [hND4] in G625A fibroblasts using the RP/KALA-MITO-Porter resulted in strong mitochondrial transgene expression.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0168-3659
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.jconrel.2018.02.005