Engineering molecular circuitry with DNA
Georg Seelig
UW EE and CSE
Biological organisms process information and control cellular behavior using sophisticated biochemical circuits. In order to engineer circuits of similar complexity and thus "program" biology we need to develop molecular tools for (i) accurate detection of complex cellular states and (ii) control and modulation of those states.
As a first step towards addressing these challenges we have recently implemented multi-layered nucleic acid logic circuits that function reliably in an aqueous, cell-free environment. Hybridization reactions provide the free energy to move computation forward and Watson-Crick base pairing between modular recognition domains determines the connectivity of circuit components. Circuits embody key design principles of digital electronics: logic, cascading, restoration, fan-in/fan-out and modularity. Our approach demonstrates that adherence to these principles provides a viable path towards the de novo construction of biochemical reaction networks.
Working in vitro it is possible to rapidly scale up circuit complexity, to explore new modes of molecular computation, and to quantitatively characterize circuit behavior without degradation of DNA or RNA that may occur in a cell. These experiments represent a foundation for developing in vivo computation using related molecular schemes.
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