DNA Condensates Enable Crosstalk-Free Operation of Identical DNA Computing Cascades.

DNA strand displacement reactions (SDR) have enabled the development of biosensing devices, molecular machines, and molecular computing. However, the need for high sequence orthogonality poses a major challenge to the modular integration and scaling of DNA SDR networks into more complex systems capable of advanced or parallel functions. Here, we propose the use of liquid-like DNA condensates with addressable barcodes for confining DNA SDR networks for parallel and selective operation of near-identical circuits that would otherwise show undesired crosstalk in a homogeneous solution. By introducing Transducer modules, specific inputs can be recognized by corresponding condensates and converted to a unified Messenger for triggering downstream DNA processing locally. This allows orthogonal execution of DNA SDRs of the same sequence design in different compartments in parallel without crosstalk and interference. Our strategy contributes a facile approach to enhance modularity and scalability in DNA SDR network design, paving the way for more sophisticated and complex functionalities.