Sahishnu Patel1, Sy-Tsong Dean Chueng1, Perry T. Yin2, Kholud Dardir1, Zhichao Song4, Nicholas Pasquale1, Prof. Kelvin Kwan4, Prof. Hiroshi Sugiyama3 andProf. Ki-Bum Lee1,2,*
1 Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
2 Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA)
3 Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, 606-8501 (Japan)
4 Department of Cell Biology & Neuroscience, W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA)
Even though gene repression is a powerful approach to exogenously regulate cellular behavior, developing a platform to effectively repress targeted genes, especially for stem-cell applications, remains elusive. Herein, we introduce a nanomaterial-based platform that is capable of mimicking the function of transcription repressor proteins to downregulate gene expression at the transcriptional level for enhancing stem-cell differentiation. We developed the “NanoScript” platform by integrating multiple gene repression molecules with a nanoparticle. First, we show a proof-of-concept demonstration using a GFP-specific NanoScript to knockdown GFP expression in neural stem cells (NSCs-GFP). Then, we show that a Sox9-specific NanoScript can repress Sox9 expression to initiate enhanced differentiation of NSCs into functional neurons. Overall, the tunable properties and gene-knockdown capabilities of NanoScript enables its utilization for gene-repression applications in stem cell biology.
Keywords : gene knockdown; NanoScript; nanoparticles; neuronal differentiation; transcription repressor proteins