Empowering DNA nanotechnology with xeno-nucleic acids

Deoxyribonucleic acid (DNA) nanotechnology has unlocked unparalleled precision in bottom-up construction of nanoscale objects and devices, yet the four natural building blocks impose inherent limits on biostability, chemical diversity, and structural adaptability [1].Xeno-nucleic acids (XNAs) are synthetic genetic polymers, typically comprising unnatural sugars (or congeners), non-canonical base pairs, or backbone linkages (Figure 1).XNAs with backbone modifications often exhibit enhanced nuclease resistance and distinct helical properties.In contrast, unnatural base pairs exploit alternative hydrogen-bonding patterns or are stabilized by a combination of shape complementarity, hydrophobic interactions, and packing forces.By integrating XNA motifs into DNA frameworks or replacing the entire backbone, scientists have created hybrid and fully XNA nanostructures with enhanced stability, new morphologies, and tailored biological functions.This Perspective highlights recent breakthroughs in which XNA chemistry meets DNA nanotechnology, focusing on the design principles, structural outcomes, and unique properties imparted by XNA.