Inducing Stem Cell Myogenesis Using NanoScript
Sahishnu Patel †, Perry T. Yin ‡, Hiroshi Sugiyama §∥, and Ki-Bum Lee *†‡
†Department of Chemistry and Chemical Biology and ‡Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey 07102, United States §Institute for Integrated Cell-Material Sciences (iCeMS) and ∥Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8501, Japan
*Correspondence to Ki-Bum Lee
Transcription factors (TFs) are multidomain proteins that play a critical role in orchestrating stem cell differentiation, but several limitations hinder the full potential of TF-based gene regulation. Here we report a unique strategy to emulate TFs and differentiate stem cells in a nonviral approach using an artificial, nanoparticle-based transcription factor called NanoScript. The NanoScript platform consists of a gold nanoparticle functionalized with small molecules that mimic the various domains of TFs. As a result, NanoScript mimics the function and structure of TF proteins. Specifically, NanoScript was designed to regulate muscle cell differentiation by targeting myogenic regulatory factors (MRFs), which play an important role in inducing myogenesis. This NanoScript-MRF is stable in physiological environments, localizes within the nucleus, induces differentiation of adipose-derived mesenchymal stem cells into mature muscle cells in 7 days, and is naturally excreted from induced muscle cells. As such, NanoScript represents a safe and powerful tool for applications requiring gene manipulation.
Keywords: myogenesis; stem cell differentiation; nanoparticle-based genetic manipulation; transcription factors; nonviral delivery