A General and Scalable DNA Nano-chip with Fully Localized Architecture Enables Biocomputing in Living cells and Precisely Induces Cell Apoptosis

Abstract

DNA logic circuits have made important progress towards mimicking functions analogous to the silicon-based electronic circuit. However, limitation in the orthogonality of free-floating DNA logic components and difficulty in controlling the intrinsically random collision of DNA molecular, the complexity, scalability, and information processing ability of DNA circuits were still constrained. Here, we demonstrated a general and scalable DNA nano-chip by integration of multilayer basic DNA logic gates on a DNA origami. 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 reactive DNA components on a DNA origami according to the wiring instructions, that established the generality and the scalability of our DNA origami-based nano-chips. We showed that up to 11 addressable logical components were reconfigured in a single nano-chip for seven-inputs multi-levels logic cascading and parallel biocomputing, executing highly complex task. 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 to perform more efficient biocomputing both in solution and in living cells. Thus, we anticipate our strategy will hold great potential for building complex DNA computing networks to perform powerful biological functions.