Modified aptamers enable quantitative sub-10-nm cellular DNA-PAINT imaging

Although current implementations of super-resolution microscopy are technically approaching true molecular-scale resolution, this has not translated to imaging of biological specimens, because of the large size of conventional affinity reagents. Here we introduce slow off-rate modified aptamers (SOMAmers) as small and specific labeling reagents for use with DNA points accumulation in nanoscale topography (DNA-PAINT). To demonstrate the achievable resolution, specificity, and multiplexing capability of SOMAmers, we labeled and imaged both transmembrane and intracellular targets in fixed and live cells. Slow off-rate modified aptamer (SOMAmer) reagents are small and versatile probes for DNA-PAINT super-resolution microscopy that enable multiplexed, quantitative, and high-resolution imaging in fixed and live cells.