title: Induction of stem-cell-derived functional neurons by NanoScript-based gene repression.
abstract: 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.
authors: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
authors: Sahishnu
authors: S
authors: Patel
authors: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
authors: Sy-Tsong Dean
authors: ST
authors: Chueng
authors: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA).
authors: Perry T
authors: PT
authors: Yin
authors: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
authors: Kholud
authors: K
authors: Dardir
authors: Department of Cell Biology & Neuroscience, W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA).
authors: Zhichao
authors: Z
authors: Song
authors: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/
authors: Nicholas
authors: N
authors: Pasquale
authors: Department of Cell Biology & Neuroscience, W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA).
authors: Kelvin
authors: K
authors: Kwan
authors: Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, 606-8501 (Japan).
authors: Hiroshi
authors: H
authors: Sugiyama
authors: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/. kblee@rutgers.edu.|Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA). kblee@rutgers.edu.
authors: Ki-Bum
authors: KB
authors: Lee
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism*; D032701:Biomimetics / Q000379:methods*; D015870:Gene Expression; D055785:Gene Knockdown Techniques / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009757:Nylons / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics
chemical_list: D009757:Nylons; D012097:Repressor Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D049452:Green Fluorescent Proteins
keywords: NanoScript; gene knockdown; nanoparticles; neuronal differentiation; transcription repressor proteins