論文 - 詳細
| RRC ID | 52679 |
|---|---|
| 著者 | Takashina T, Koyama T, Nohara S, Hasegawa M, Ishiguro A, Iijima K, Lu J, Shimura M, Okamura T, Sakuma T, Yamamoto T, Ishizaka Y. |
| タイトル | Identification of a cell-penetrating peptide applicable to a protein-based transcription activator-like effector expression system for cell engineering. |
| ジャーナル | Biomaterials |
| Abstract |
Cellular reprogramming is a promising technology in regenerative medicine, but most studies have been performed by using expression vectors. For future clinical applications, it is necessary to establish a system in which cell engineering can be manipulated without any risk of damaging the genome. Here, we identified a cell-penetrating peptide composed of 10 amino acids (RIFIHFRIGC) with nuclear trafficking activity and found that it was significantly more potent than a Tat-derived peptide or polyarginine peptide (R11). We named the peptide "nuclear trafficking peptide" (NTP) and applied it to a protein-based artificial transcription factor (NTP-ATF), which was composed of a transcription activator-like effector and transcription domain (VP64). An NTP-ATF designed to the proximal promoter region of the microRNA-302/367 cluster efficiently induced endogenous RNA expression at an extremely low concentration (0.25 nM), and repetitive treatment of mouse embryonic fibroblasts with NTP-ATF generated induced pluripotent stem-like cells, which gave chimeric mice. Together with the observation that recombinant NTP-ATF protein did not induce any apparent cytotoxicity, we propose that NTP-ATF is a promising system for cellular reprogramming applicable to regenerative medicine. |
| 巻・号 | 173 |
| ページ | 11-21 |
| 公開日 | 2018-8-1 |
| DOI | 10.1016/j.biomaterials.2018.04.040 |
| PII | S0142-9612(18)30307-7 |
| PMID | 29734017 |
| MeSH | Active Transport, Cell Nucleus Animals Cell Engineering / methods* Cell Line, Tumor Cell Nucleus / metabolism Cell Survival Cell-Penetrating Peptides / genetics Cell-Penetrating Peptides / metabolism* Cell-Penetrating Peptides / pharmacology Cellular Reprogramming Chimera Fibroblasts / cytology Fibroblasts / drug effects Fibroblasts / metabolism Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / drug effects Induced Pluripotent Stem Cells / metabolism Mice MicroRNAs / genetics MicroRNAs / metabolism Recombinant Proteins / chemistry Recombinant Proteins / metabolism Recombinant Proteins / pharmacology Transcription Activator-Like Effectors / genetics Transcription Activator-Like Effectors / metabolism* Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 10.317 |
| 引用数 | 3 |
| 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 | 3 |
| 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 | MRC-5(RCB0211) HT1080(RCB1956) |