Sahishnu Patel^†, Dongju Jung ^‡, Perry T. Yin ^§, Peter Carlton ^‡, Makoto Yamamoto^∥, Toshikazu Bando^∥, Hiroshi Sugiyama ^‡∥, and Ki-Bum Lee ^†§*

^† Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States
^‡ Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan
^§ Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States
^∥Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan

^*Correspondence to Ki-Bum Lee

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.

Keywords: nanoparticle-based genetic manipulation; transcription factor proteins; gene activation; synthetic transcription factors; nonviral delivery