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Induction of Stem‐Cell‐Derived Functional Neurons by NanoScript‐Based Gene Repression
Author(s) -
Patel Sahishnu,
Chueng SyTsong Dean,
Yin Perry T.,
Dardir Kholud,
Song Zhichao,
Pasquale Nicholas,
Kwan Kelvin,
Sugiyama Hiroshi,
Lee KiBum
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201504902
Subject(s) - gene knockdown , psychological repression , neural stem cell , stem cell , microbiology and biotechnology , repressor , biology , regulation of gene expression , gene expression , cellular differentiation , transcription factor , gene , gene regulatory network , computational biology , genetics
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.