Advanced Synthesis of Spherical Nucleic Acids: A Limit-Pursuing Game with Broad Implications

Spherical nucleic acids (SNAs) consist of DNA strands arranged radially and packed densely on the surface of nanoparticles. Due to their unique properties, which are not found in naturally occurring linear or circular DNA, SNAs have gained widespread attention in fields such as sensing, nanomedicine, and colloidal assembly. The rapidly evolving applications of SNAs have driven a modernization of their syntheses to meet different needs. Recently, several advanced approaches have emerged, enabling ultrafast, quantitative, and low-cost SNA synthesis with maximal DNA grafting through "counterintuitive" processes like freezing and dehydration. This concept paper discusses these critical developments from a synthetic perspective, focusing on their underlying mechanisms and broad implications, with a goal of inspiring future research in related fields.