A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice

Science. 2011 Jun 24;332(6037):1565-8. doi: 10.1126/science.1203535.

Abstract

Synthetic biology has advanced the design of genetic devices that can be used to reprogram metabolic activities in mammalian cells. By functionally linking the signal transduction of melanopsin to the control circuit of the nuclear factor of activated T cells, we have designed a synthetic signaling cascade enabling light-inducible transgene expression in different cell lines grown in culture or bioreactors or implanted into mice. In animals harboring intraperitoneal hollow-fiber or subcutaneous implants containing light-inducible transgenic cells, the serum levels of the human glycoprotein secreted alkaline phosphatase could be remote-controlled with fiber optics or transdermally regulated through direct illumination. Light-controlled expression of the glucagon-like peptide 1 was able to attenuate glycemic excursions in type II diabetic mice. Synthetic light-pulse-transcription converters may have applications in therapeutics and protein expression technology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bioreactors
  • Blood Glucose / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation*
  • Genes, Reporter
  • Genetic Engineering / methods*
  • Glucagon-Like Peptide 1 / genetics
  • Glucagon-Like Peptide 1 / metabolism
  • Homeostasis
  • Humans
  • Insulin / blood
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Light Signal Transduction
  • Light*
  • Mice
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Optical Fibers
  • Rod Opsins / genetics
  • Rod Opsins / metabolism
  • Signal Transduction
  • Synthetic Biology / methods*
  • Transcription, Genetic*
  • Transfection
  • Transgenes

Substances

  • Blood Glucose
  • GPI-Linked Proteins
  • Insulin
  • Isoenzymes
  • NFATC Transcription Factors
  • Rod Opsins
  • melanopsin
  • Glucagon-Like Peptide 1
  • Alkaline Phosphatase
  • alkaline phosphatase, placental