Induction of stem-cell-derived functional neurons by NanoScript-based gene repression.

Angew Chem Int Ed Engl

Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (USA) http://kblee.rutgers.edu/.

Published: October 2015

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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568028PMC
http://dx.doi.org/10.1002/anie.201504902DOI Listing

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