Vision of Life's Code: Molecular Probe Nanoarchitectonics for Deep RNA/DNA Illumination

Visualization of RNA and DNA provides a window of opportunity for the early detection of multiple diseases and approaches to manipulate them before any pathological processes occur. However, current imaging systems often fail to meet these demands due to the need for multiple RNA and DNA chemical probes, which increases experimental complexity, reduces awareness of false positives, and limits imaging accuracy in complex biosystems. In this work, we identify the key challenges associated with using multiple probes for RNA and DNA imaging and analyze the mechanisms and performance of existing imaging tools. This article also introduces a conceptual framework and proposes a multidisciplinary framework to guide the development of next-generation imaging technologies. Furthermore, we highlight how nanoarchitectonics-based molecular design can enable single-step multiplexed RNA-DNA imaging. Our goal is to provide valuable resources for both biologists and probe developers for choosing suitable molecular probes and further advancing their design, from initial concepts to commercial products─all from a biologist's perspective.