title: NanoScript: a nanoparticle-based artificial transcription factor for effective gene regulation.
abstract: 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.
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
authors.forename: Sahishnu
authors.initials: S
authors.lastname: Patel
authors.forename: Dongju
authors.initials: D
authors.lastname: Jung
authors.forename: Perry T
authors.initials: PT
authors.lastname: Yin
authors.forename: Peter
authors.initials: P
authors.lastname: Carlton
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Ki-Bum
authors.initials: KB
authors.lastname: Lee
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D006046:Gold / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles; D053758:Nanoparticles; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D010455:Peptides; D014157:Transcription Factors; D006046:Gold
keywords: gene activation; nanoparticle-based genetic manipulation; nonviral delivery; synthetic transcription factors; transcription factor proteins