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Induction of Stem Cell-derived Functional Neurons via NanoScript-based Gene Repression
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 funct...
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Published in: | Angewandte Chemie International Edition 2015-08, Vol.54 (41), p.11983-11988 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | 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.
It Will Knock You Down:
A NanoScript-based platform is designed to knock down transcriptional gene expression in stem cells. The tunable and non-viral NanoScript platform, which is comprised of a nanoparticle functionalized with specific small molecules, has been demonstrated to both effectively knock down GFP in GFP-labeled neural stem cells (NSCs), and repress
Sox9
expression in NSCs to induce differentiation into functional neurons. |
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ISSN: | 1433-7851 1521-3773 |
DOI: | 10.1002/anie.201504902 |