A tunable dual-promoter integrator for targeting of cancer cells

Lior Nissim, Roy H. Bar-Ziv

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Precise discrimination between similar cellular states is essential for autonomous decision-making scenarios, such as in vivo targeting of diseased cells. Discrimination could be achieved by delivering an effector gene expressed under a highly active context-specific promoter. Yet, a single-promoter approach has linear response and offers limited control of specificity and efficacy. Here, we constructed a dual-promoter integrator, which expresses an effector gene only when the combined activity of two internal input promoters is high. A tunable response provides flexibility in choosing promoter inputs and effector gene output. Experiments using one premalignant and four cancer cell lines, over a wide range of promoter activities, revealed a digital-like response of input amplification following a sharp activation threshold. The response function is cell dependent with its overall magnitude increasing with degree of malignancy. The tunable digital-like response provides robustness, acts to remove input noise minimizing false-positive identification of cell states, and improves targeting precision and efficacy.

Original languageAmerican English
Article number444
JournalMolecular Systems Biology
Volume6
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • cancer
  • gene therapy
  • signal integration
  • synthetic biology
  • systems biology

Fingerprint

Dive into the research topics of 'A tunable dual-promoter integrator for targeting of cancer cells'. Together they form a unique fingerprint.

Cite this