Noncanonical Condensation of Nucleic Acid Chains by Hydrophobic Gold Nanocrystals

Nucleic acid condensatesare essential for various biological processesand have numerous applications in nucleic acid nanotechnology, genetherapy, and mRNA vaccines. However, unlike the in vivo condensationthat is dependent on motor proteins, the in vitro condensation efficiencyremains to be improved. Here, we proposed a hydrophobic interaction-drivenmechanism for condensing long nucleic acid chains using atomicallyprecise hydrophobic gold nanoclusters (Au NCs). We found that hydrophobicAu NCs could condense long single-stranded DNA or RNA to form compositesof spherical nanostructures, which further assembled into bead-shapedsuprastructures in the presence of excessive Au NCs. Thus, suprastructuresdisplayed gel-like behaviors, and Au NCs could diffuse freely insidethe condensates, which resemble the collective motions of condensincomplexes inside chromosomes. The dynamic hydrophobic interactionsbetween Au NCs and bases allow for the reversible release of nucleicacids in the presence of mild triggering agents. Our method representsa significant advancement toward the development of more efficientand versatile nucleic acid condensation techniques.