Left-handed DNA for efficient highly multiplexed imaging at single-protein resolution.

Unterauer, Eduard M; Schentarra, Eva-Maria; Pachmayr, Isabelle; Tashrin, Taisha; Kwon, Jisoo; Strauss, Sebastian; Jevdokimenko, Kristina; Kowalewski, Rafal et al. · Nat Commun · 2025

basic_science · Level V

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Abstract

Multiplexed super-resolution microscopy enables spatial proteomics at single-protein resolution, but current methods often depend on secondary labels, complicating implementation and limiting throughput. We introduce a streamlined approach that combines speed-optimized DNA-PAINT sequences with their mirror-image analogs (left-handed DNA), enabling rapid and efficient 12-plex imaging. Validated on synthetic and cellular benchmarks, our method maps dense neuronal interactomes in 3D with 15 nm spatial resolution across a 200 × 200 µm<sup>2</sup> field of view.

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