ATP-Powered Signaling between Synthetic and Living Cells

ATP is the energy currency of life and overabundant in the tumor microenvironment, where it has been suggested as a target for cancer therapy. We introduce ATP-dissipative delivery of DNA signals from synthetic cells to living cells by exploiting an ATP-driven reaction network that transiently ejects DNA Signal strands from the shielded synthetic cell interior to the extracellular medium of living cells. We customize the Signal for intracellular uptake or for extracellular instruction using a cytokine-ssDNA chimera that can trigger efficient intracellular downstream signaling programs. Our study discusses details of system design on a timer circuit and synthetic cell level, system integration challenges, and how ATP concentrations regulate the transient delivery. The strategy can be extended to deliver therapeutic oligonucleotides for applications in gene therapy and gene silencing. For cancer therapy, it can use naturally enhanced ATP levels to induce selective delivery of therapeutic oligonucleotides.