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
リソース情報
ヒト・動物細胞 MRC-5(RCB0211) HT1080(RCB1956)