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

Author

Listed:
  • Eduard M. Unterauer

    (Ludwig Maximilian University
    Max Planck Institute of Biochemistry)

  • Eva-Maria Schentarra

    (Ludwig Maximilian University
    Max Planck Institute of Biochemistry)

  • Isabelle Pachmayr

    (Max Planck Institute of Biochemistry
    Ludwig Maximilian University)

  • Taisha Tashrin

    (Max Planck Institute of Biochemistry)

  • Jisoo Kwon

    (Ludwig Maximilian University)

  • Sebastian Strauss

    (Max Planck Institute of Biochemistry)

  • Kristina Jevdokimenko

    (University Medical Center Göttingen)

  • Rafal Kowalewski

    (Ludwig Maximilian University
    Max Planck Institute of Biochemistry)

  • Felipe Opazo

    (University Medical Center Göttingen
    University Medical Center Göttingen
    NanoTag Biotechnologies GmbH)

  • Eugenio F. Fornasiero

    (University Medical Center Göttingen
    University of Trieste)

  • Luciano A. Masullo

    (Max Planck Institute of Biochemistry)

  • Ralf Jungmann

    (Ludwig Maximilian University
    Max Planck Institute of Biochemistry)

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 µm2 field of view.

Suggested Citation

  • Eduard M. Unterauer & Eva-Maria Schentarra & Isabelle Pachmayr & Taisha Tashrin & Jisoo Kwon & Sebastian Strauss & Kristina Jevdokimenko & Rafal Kowalewski & Felipe Opazo & Eugenio F. Fornasiero & Luc, 2025. "Left-handed DNA for efficient highly multiplexed imaging at single-protein resolution," Nature Communications, Nature, vol. 16(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64228-x
    DOI: 10.1038/s41467-025-64228-x
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    References listed on IDEAS

    as
    1. Maja Klevanski & Frank Herrmannsdoerfer & Steffen Sass & Varun Venkataramani & Mike Heilemann & Thomas Kuner, 2020. "Automated highly multiplexed super-resolution imaging of protein nano-architecture in cells and tissues," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    2. Alex M. Valm & Sarah Cohen & Wesley R. Legant & Justin Melunis & Uri Hershberg & Eric Wait & Andrew R. Cohen & Michael W. Davidson & Eric Betzig & Jennifer Lippincott-Schwartz, 2017. "Applying systems-level spectral imaging and analysis to reveal the organelle interactome," Nature, Nature, vol. 546(7656), pages 162-167, June.
    Full references (including those not matched with items on IDEAS)

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