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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月2日

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  • Eduard M. Unterauer,
  • Eva-Maria Schentarra,
  • Isabelle Pachmayr,
  • Taisha Tashrin,
  • Jisoo Kwon,
  • Sebastian Strauss,
  • Kristina Jevdokimenko,
  • Rafal Kowalewski,
  • Felipe Opazo,
  • Eugenio F. Fornasiero,
  • Luciano A. Masullo,
  • Ralf Jungmann

摘要

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 µm2 field of view.