NanoScript: a nanoparticle-based artificial transcription factor for effective gene regulation.
NanoScript: a nanoparticle-based artificial transcription factor for effective gene regulation.
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DOI：
10.1021/nn501589f
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发表时间：
2014-09-23
期刊：
影响因子：
17.1
通讯作者：
Lee, Ki-Bum
中科院分区：
文献类型：
--
作者：
Patel, Sahishnu;Jung, Dongju;Yin, Perry T.;Carlton, Peter;Yamamoto, Makoto;Bando, Toshikazu;Sugiyama, Hiroshi;Lee, Ki-Bum
关键词：
转录因子（TF）蛋白是转录活性和基因表达的主要调节因子。基于TF的基因调控是许多生物学应用的有前途的方法;然而，一些限制阻碍了TF的全部潜力。在此，我们开发了一种人工的，基于纳米颗粒的转录因子，称为NanoScript，其设计用于模拟TF的结构和功能。NanoScript是通过将功能肽和称为合成转录因子的小分子（模拟单个TF结构域）连接到金纳米颗粒上而构建的。我们证明，NanoScript定位在细胞核内，并启动超过15倍的报告质粒的转录。此外，NanoScript可以以非病毒方式有效地转录内源DNA上的靶基因。由于NanoScript是TF蛋白的功能复制品和可调基因调控平台，因此它在各种干细胞应用中具有巨大潜力。
Transcription factor (TF) proteins are master regulators of transcriptional activity and gene expression. TF-based gene regulation is a promising approach for many biological applications; however, several limitations hinder the full potential of TFs. Herein, we developed an artificial, nanoparticle-based transcription factor, termed NanoScript, which is designed to mimic the structure and function of TFs. NanoScript was constructed by tethering functional peptides and small molecules called synthetic transcription factors, which mimic the individual TF domains, onto gold nanoparticles. We demonstrate that NanoScript localizes within the nucleus and initiates transcription of a reporter plasmid by over 15-fold. Moreover, NanoScript can effectively transcribe targeted genes on endogenous DNA in a nonviral manner. Because NanoScript is a functional replica of TF proteins and a tunable gene-regulating platform, it has great potential for various stem cell applications.
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DOI：
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