NanoScript: A Nanoparticle-Based Artificial Transcription Factor for Effective Gene Regulation

NanoScript_emulates_TF_Structure_and_Function_large.jpg

Highlights

  • Transcription Factors (TF) are proteins that regulate transcription and gene expression
  • NanoScript is an versatile, nanoparticle-based platform that mimics TF structure and biological function
  • NanoScript is stable in physiological environments and localizes within the nucleus
  • NanoScript initiates targeted gene expression by over 15-fold to 30 fold, which would be critical for stem cell differentiation and cellular reprogramming
  • NanoScript transcribes endogenous genes on native DNA in a non-viral manner

Abstract

Transcription factor (TF) proteins are master regulators of transcriptional activity and gene expression. TF-based gene regulation is an essential approach for many biological applications such as stem cell differentiation and cellular programming, however, several limitations hinder the full potential of TFs.

To address this challenge, researchers in Prof. KiBum Lee’s group (Sahishnu Patel and Perry Yin) 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. They demonstrated that NanoScript localizes within the nucleus and initiates transcription of a targeted gene with high efficiency. Moreover, NanoScript can effectively transcribe targeted genes on endogenous DNA in a non-viral manner.

NanoScript is a functional replica of TF proteins and a tunable gene-regulating platform. NanoScript has two attractive features that make this the perfect platform for stem cell-based application. First, because gene regulation by NanoScript is non-viral, it serves as an attractive alternative to current differentiation methods that use viral vectors. Second, by simply rearranging the sequence of one molecule on NanoScript, NanoScript can target any differentiation-specific genes and induce differentiation, and thus has excellent prospect for applications in stem cell biology and cellular reprogramming.

Group Members: 
Prof_KiBum_Lee_200-200.jpg
Prof. KiBum Lee
Sahishnu_Patel_r.jpg
Sahishnu Patel
PerryYin_r.jpg
Perry Yin
Year of Research Highlight: 
2014