論文 - 詳細
| RRC ID | 55981 |
|---|---|
| 著者 | Ishikawa T, Somiya K, Munechika R, Harashima H, Yamada Y. |
| タイトル | Mitochondrial transgene expression via an artificial mitochondrial DNA vector in cells from a patient with a mitochondrial disease. |
| ジャーナル | J Control Release |
| Abstract |
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. |
| 巻・号 | 274 |
| ページ | 109-117 |
| 公開日 | 2018-3-28 |
| DOI | 10.1016/j.jconrel.2018.02.005 |
| PII | S0168-3659(18)30065-8 |
| PMID | 29408532 |
| MeSH | Animals DNA, Mitochondrial / administration & dosage* DNA, Mitochondrial / genetics Gene Transfer Techniques* Genetic Therapy / methods Humans Male Mice, Inbred C57BL Mitochondria / genetics* Mitochondria / metabolism Mitochondrial Diseases / therapy* Transfection Transgenes |
| IF | 7.901 |
| 引用数 | 15 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa |