Left-handed DNA for efficient highly multiplexed imaging at single-protein resolution
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.
Authors
- Rafal Kowalewski
- Eduard M. Unterauer
- Eva-Maria Schentarra (ORCID: https://orcid.org/0000-0002-3243-8870)
- Eugenio F. Fornasiero
- Sebastian Strauss (ORCID: https://orcid.org/0000-0002-4653-1451)
- Ralf Jungmann (ORCID: https://orcid.org/0000-0003-4607-3312)
- Kristina Jevdokimenko
- Isabelle Pachmayr (ORCID: https://orcid.org/0000-0002-3422-8340)
- Jisoo Kwon
- Luciano A. Masullo (ORCID: https://orcid.org/0000-0001-8664-5448)
- Felipe Opazo (ORCID: https://orcid.org/0000-0002-4968-9713)
- Taisha Tashrin
Institutions
- University of Trieste (IT)
- Center for NanoScience (DE)
- Universitätsmedizin Göttingen (DE)
- Max Planck Institute of Biochemistry (DE)
- University of Göttingen (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-02
- DOI
- https://doi.org/10.1038/s41467-025-64228-x
- Citations
- 2
- Primary Topic
- Advanced Fluorescence Microscopy Techniques
- Type
- article
- Field-Weighted Citation Impact
- 3.27
Funders
- Max-Planck-Förderstiftung
- European Commission
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Max-Planck-Gesellschaft
- International Max Planck Research School for Advanced Methods in Process and Systems Engineering