Upconversion Luminescence-Controlled DNA Computation for Spatiotemporally Resolved, Multiplexed Molecular Imaging

DNA-based molecular circuits able to perform complex information processing in biological systems are highly desirable. However, conventional DNA circuits are constitutively always in an ON state and immediately operate when they meet the biomolecular inputs, precluding precise molecular computation at a desired time and in a desired site. In this work, we report a conceptual methodology for the construction of photonic nanocircuits that enable DNA molecular computation in vitro and in vivo with high spatial precision. Upon remote activation by spatially restricted NIR-light input, two types of cancer biomarker inputs can sequentially trigger conformational changes of the DNA circuit through a structure-switching aptamer and toehold-mediated strand exchange, leading to release of a signaling output. Of note, the NIR-light-gated nanocircuit allows for intended control over the specific timing and location of DNA computation, providing spatial and temporal capabilities for multiplexed imaging. Furthermore, an OR-AND-gated nanocircuit of higher complexity was designed to illustrate the versatility of our approach. The present work illustrates the potential of the use of upconversion nanotechnology as a regulatory tool for spatial and temporal control of DNA computation in cells and animals.

Automated summary

This study introduces a new approach for achieving high-precision DNA molecular computation using photonic nanocircuits, allowing spatial and temporal control in vitro and in vivo. Researchers designed a circuit that can track cancer biomarkers and output signals, as well as demonstrated a more complex gated circuit, showcasing the versatility and potential of the method.