A general and scalable DNA nano-chip with a fully localized architecture enables biocomputing in living cells and...

DNA logic circuits have made important progress towards mimicking functions analogous to silicon-based electronic circuits. However, because of limitations in the orthogonality of free-floating DNA logic components and difficulty in controlling the intrinsically random collision of DNA molecules, the complexity, scalability, and information processing ability of DNA circuits are still constrained. Here, we demonstrate a general and scalable DNA nano-chip by integration of multilayer basic DNA logic gates on a DNA origami structure. We created basic DNA logic gates based on DNA localized strand displacement reactions. The basic logic gates were modularly combined into circuits by spatially arranging all of the reactive DNA components on a DNA origami structure according to the wiring instructions, establishing the generality and scalability of our DNA origami-based nano-chips. We showed that up to 11 addressable logic components were reconfigured in a single nano-chip for seven-input multi-level logic cascading and parallel biocomputing, executing highly complex tasks. We further integrated three layers of cascade logic units on the nano-chip for intracellular molecular biocomputing to execute precise identification and specific killing of tumor cells. Compared to circuits with diffusible components, our nano-chip enabled the performance of more efficient biocomputing both in solution and in living cells. Thus, we anticipate that our strategy will hold great potential for building complex DNA computing networks to perform powerful biological functions.