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ACS Synth Biol. 2013 Aug 16;2(8):418-24. doi: 10.1021/sb300107h. Epub 2013 Mar 6.

Modular design of a synthetic payload delivery device.


Predictable engineering of complex biological behaviors using characterized molecular functions remains a key challenge in synthetic biology. To explore the process of engineering biological behaviors, we applied a modular design strategy to the development of E. coli that deliver macromolecules to the cytoplasm of cancer cells in vitro. First, we specified five abstract, qualitative behaviors that would act in concert to achieve payload delivery. Drawing from disparate sources of previously described genetic components, we then designed, constructed, and tested individual genetic circuits to implement each module. Subsequent coupling of the modules and system optimization, aided by quantitative predictions, generated a system that delivers proteins to 80% of targeted cancer cells. Development of an effective delivery system provides strong evidence that advanced cellular behaviors, not just transcriptional circuits, can be rationally decomposed into a series of functional genetic modules and then constructed to achieve the target activity with the existing synthetic biology toolkit.

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