Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 58, Issue 50, Pages 18186-18190Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201908971
Keywords
aptamers; DNA nanotechnology; logic gates; receptor assembly; signal transduction
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Funding
- National Natural Science Foundation of China [21622502, U1505221, 21635002, 21605023]
- Natural Science Foundation of Fujian Province of China [2017J06004]
- Shanghai Rising-Star Program [19QA1405400]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT15R11]
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Programming cells to sense multiple inputs and activate cellular signal transduction cascades is of great interest. Although this goal has been achieved through the engineering of genetic circuits using synthetic biology tools, a nongenetic and generic approach remains highly demanded. Herein, we present an aptamer-controlled logic receptor assembly for modulating cellular signal transduction. Aptamers were engineered as robotic arms to capture target receptors (c-Met and CD71) and a DNA logic assembly functioned as a computer processor to handle multiple inputs. As a result, the DNA assembly brings c-Met and CD71 into close proximity, thus interfering with the ligand-receptor interactions of c-Met and inhibiting its functions. Using this principle, a set of logic gates was created that respond to DNA strands or light irradiation, modulating the c-Met/HGF signal pathways. This simple modular design provides a robust chemical tool for modulating cellular signal transduction.
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