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

Angew Chem Int Ed Engl. 2015 Oct 5;54(41):11983-8. doi: 10.1002/anie.201504902. Epub 2015 Aug 20.

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.

Keywords: NanoScript; gene knockdown; nanoparticles; neuronal differentiation; transcription repressor proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomimetic Materials / chemistry
  • Biomimetic Materials / metabolism*
  • Biomimetics / methods*
  • Gene Expression
  • Gene Knockdown Techniques / methods*
  • Green Fluorescent Proteins / genetics
  • Humans
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism*
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurogenesis*
  • Neurons / cytology*
  • Neurons / metabolism
  • Nylons / chemistry
  • Nylons / metabolism
  • Promoter Regions, Genetic
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism
  • SOX9 Transcription Factor / genetics

Substances

  • Nylons
  • Repressor Proteins
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Green Fluorescent Proteins