Frontiers of RNA Nanotechnology: Designing the Future of Synthetic Biology

RNA structural biology has rapidly evolved from interpreting RNA as a passive genetic messenger to positioning it as a key programmable component for advanced bioengineering. Recent breakthroughs highlight RNA’s ability to form sophisticated nanostructures—ranging from 2D and 3D scaffolds to intricate dynamic devices—enabling highly specific molecular recognition, catalysis, and control. Within the domains of synthetic biology and cell-free systems, this versatility has unlocked new possibilities for manipulating biological information, engineering hybrid molecular machines, and building devices operating independently of living cells. Despite these strides, important questions remain about optimizing RNA stability, achieving precise functional control, and scaling the integration of RNA devices across in vivo and cell-free environments.Pioneering research has showcased RNA-based logic circuits, programmable biosensors, drug delivery vehicles, and complex synthetic circuits that operate within both cellular and cell-free contexts. Innovative selection techniques, such as combining SELEX with rational RNA nanostructure design, are producing aptamers and ribozymes with unprecedented performance and embedded functional complexity. At the same time, cell-free systems are becoming invaluable platforms for prototyping synthetic RNA devices, streamlining diagnostics, and enabling rapid, on-demand production of therapeutic compounds. However, the seamless translation of these advances from experimental to practical applications remains an ongoing challenge, particularly regarding robust design principles, large-scale implementation, and integration with computational modeling and directed molecular evolution.This Research Topic aims to advance the next generation of programmable RNA-based architectures and cell-free systems for applications in biotechnology and medicine. The primary objective is to catalyze the integration of RNA structural biology, synthetic biology, and cell-free engineering, by highlighting cutting-edge research into novel design principles, mechanisms of control, and translational applications of RNA nanotechnology. Key questions include how to harness the programmability of RNA for computation and sensing, improve targeted medicine and gene therapy, and combine experimental strategies with computational modeling and directed evolution to derive high-performance biomolecular tools.The scope of this Research Topic encompasses both fundamental and applied research into programmable RNA systems, with particular emphasis on innovative combinations of cell-free systems and rational design. Studies may range from molecular design and proof-of-concept demonstrations to translational and clinical advances in RNA-based diagnostics and therapeutics. We welcome original research, reviews, protocols, methods, and perspectives addressing, but not limited to, the following themes:- De novo design and structural characterization of RNA origami and nanostructures- RNA-based logic circuits, biosensors, and computation in cell-free and in vivo environmentsProgrammable RNA vehicles for drug delivery, gene therapy, and precision medicine- Hybrid methodologies for aptamer, ribozyme, and ligand discovery in engineered scaffolds- Integration of computational, experimental, and evolutionary approaches for RNA systems engineeringArticle types welcomed include original research, reviews, methods, protocols, and perspectives. Topic editors: Yoshiya Ikawa, Massimo Bellato Source: https://www.frontiersin.org/research-topics/77290/frontiers-of-rna-nanotechnology-designing-the-future-of-synthetic-biology