Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins

Science. 2010 Nov 26;330(6008):1251-5. doi: 10.1126/science.1192128.

Abstract

Synthetic genetic devices that interface with native cellular pathways can be used to change natural networks to implement new forms of control and behavior. The engineering of gene networks has been limited by an inability to interface with native components. We describe a class of RNA control devices that overcome these limitations by coupling increased abundance of particular proteins to targeted gene expression events through the regulation of alternative RNA splicing. We engineered RNA devices that detect signaling through the nuclear factor κB and Wnt signaling pathways in human cells and rewire these pathways to produce new behaviors, thereby linking disease markers to noninvasive sensing and reprogrammed cellular fates. Our work provides a genetic platform that can build programmable sensing-actuation devices enabling autonomous control over cellular behavior.

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

  • Alternative Splicing*
  • Apoptosis
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / genetics
  • Aptamers, Nucleotide / metabolism*
  • Capsid Proteins / metabolism
  • Cell Line
  • Cell Nucleus / metabolism
  • Exons
  • Ganciclovir / pharmacology
  • Gene Expression Regulation*
  • Gene Regulatory Networks
  • Genetic Engineering*
  • Green Fluorescent Proteins / genetics
  • Humans
  • Introns
  • Ligands
  • Mutation
  • NF-kappa B p50 Subunit / genetics
  • NF-kappa B p50 Subunit / metabolism
  • Protein Binding
  • Signal Transduction
  • Survival of Motor Neuron 1 Protein / genetics
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Transfection
  • Wnt Proteins / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Aptamers, Nucleotide
  • Capsid Proteins
  • Ligands
  • NF-kappa B p50 Subunit
  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein
  • Transcription Factor RelA
  • Wnt Proteins
  • beta Catenin
  • Green Fluorescent Proteins
  • Ganciclovir