Induction of Stem-Cell-Derived Functional Neurons by NanoScript-Based Gene Repression
Sahishnu Patel
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
Search for more papers by this authorSy-Tsong Dean Chueng
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
Search for more papers by this authorPerry T. Yin
Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA)
Search for more papers by this authorKholud Dardir
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
Search for more papers by this authorZhichao Song
Department of Cell Biology & Neuroscience, W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA)
Search for more papers by this authorNicholas Pasquale
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
Search for more papers by this authorProf. Kelvin Kwan
Department of Cell Biology & Neuroscience, W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA)
Search for more papers by this authorProf. Hiroshi Sugiyama
Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, 606-8501 (Japan)
Search for more papers by this authorCorresponding Author
Prof. Ki-Bum Lee
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA)
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/Search for more papers by this authorSahishnu Patel
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
Search for more papers by this authorSy-Tsong Dean Chueng
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
Search for more papers by this authorPerry T. Yin
Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA)
Search for more papers by this authorKholud Dardir
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
Search for more papers by this authorZhichao Song
Department of Cell Biology & Neuroscience, W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA)
Search for more papers by this authorNicholas Pasquale
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
Search for more papers by this authorProf. Kelvin Kwan
Department of Cell Biology & Neuroscience, W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA)
Search for more papers by this authorProf. Hiroshi Sugiyama
Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, 606-8501 (Japan)
Search for more papers by this authorCorresponding Author
Prof. Ki-Bum Lee
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA)
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/Search for more papers by this authorAbstract
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.
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