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Structural DNA nanotechnology enables user-prescribed design of DNA nanostructures (DNs) for biological applications, but how DN design determines their bio-distribution and cellular interactions remain poorly understood. One challenge is that current methods for tracking DN fates in situ, including fluorescent-dye labeling, suffer from low sensitivity and dye-induced artifacts. Here we present origamiFISH, a label-free and universal method for single-molecule fluorescence detection of DNAdoi:10.1101/2022.09.19.508533 fatcat:dho4l74lbvd5pp43bvovyeea5a