Nucleic acid condensates as programmable regulators of chemical reactions and catalysis.

Abstract

Nucleic acid condensates are emerging as programmable soft materials capable of organizing and regulating biochemical reactions through sequence-directed interactions. Inspired by biological membrane-less organelles formed by liquid-liquid phase separation, synthetic DNA and RNA condensates can selectively concentrate, exclude, and spatially organize biomolecules to modulate catalytic activity and reaction pathways. Recent advances in sequence design have enabled precise control over condensate assembly, phase behavior, orthogonality, and responsiveness to molecular signals. In particular, multivalent DNA and RNA motifs assembled through sticky-end or kissing-loop interactions provide versatile platforms for constructing dynamically reconfigurable reaction environments. Furthermore, coupling condensates with strand displacement circuits, reaction-diffusion systems, and catalytic feedback enables spatiotemporal regulation of reactions and condensate organization. Here, we review recent progress in synthetic nucleic acid condensates as programmable regulators of chemical reactions and catalysis, highlighting their potential as adaptive and life-like reaction environments.