Synthesizing artificial devices that redirect cellular information at will.

Abstract

Natural signaling circuits could be rewired to reprogram cells with pre-determined procedures. However, it is difficult to link cellular signals at will. Here, we describe signal-connectors<i>-</i>a series of RNA devices<i>-</i>that connect one signal to another signal at the translational level. We use them to either repress or enhance the translation of target genes in response to signals. Application of these devices allows us to construct various logic gates and to incorporate feedback loops into gene networks. They have also been used to rewire a native signaling pathway and even to create novel pathways. Furthermore, logical AND gates based on these devices and integration of multiple signals have been used successfully for identification and redirection of the state of cancer cells. Eventually, the malignant phenotypes of cancers have been reversed by rewiring the oncogenic signaling from promoting to suppressing tumorigenesis. We provide a novel platform for redirecting cellular information.