Multi-input RNAi-based logic circuit for identification of specific cancer cells

Science. 2011 Sep 2;333(6047):1307-11. doi: 10.1126/science.1205527.


Engineered biological systems that integrate multi-input sensing, sophisticated information processing, and precisely regulated actuation in living cells could be useful in a variety of applications. For example, anticancer therapies could be engineered to detect and respond to complex cellular conditions in individual cells with high specificity. Here, we show a scalable transcriptional/posttranscriptional synthetic regulatory circuit--a cell-type "classifier"--that senses expression levels of a customizable set of endogenous microRNAs and triggers a cellular response only if the expression levels match a predetermined profile of interest. We demonstrate that a HeLa cancer cell classifier selectively identifies HeLa cells and triggers apoptosis without affecting non-HeLa cell types. This approach also provides a general platform for programmed responses to other complex cell states.

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

  • Apoptosis*
  • Biomarkers, Tumor
  • Cell Line
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks*
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • RNA Interference*
  • Synthetic Biology / methods
  • Transfection
  • bcl-2-Associated X Protein / genetics


  • BAX protein, human
  • Biomarkers, Tumor
  • MicroRNAs
  • bcl-2-Associated X Protein