Updated
Updated · Nature.com · Apr 22
Banerjee, Anand, Srivastava et al develop 12 speed-optimized DNA-PAINT sequences for multiplexed nuclear imaging
Updated
Updated · Nature.com · Apr 22

Banerjee, Anand, Srivastava et al develop 12 speed-optimized DNA-PAINT sequences for multiplexed nuclear imaging

3 articles · Updated · Nature.com · Apr 22
  • The team achieved 9-plex super-resolution imaging of nuclear targets in single cells within four hours, reaching localization precision as fine as 8 nanometers.
  • Their expanded DNA-PAINT sequence repertoire enables simultaneous visualization of up to twelve targets, accelerating acquisition times and mapping chromatin organization changes after transcription inhibition.
  • This advancement addresses previous limitations in DNA-PAINT multiplexing and speed, supporting broader adoption for high-resolution spatial proteomics and cellular imaging applications.
As DNA-PAINT gets a major speed boost, are competing high-resolution imaging techniques becoming obsolete?
With cellular imaging now 12 times more complex, what biological mysteries can we finally solve?
Could these ultra-fast cellular snapshots become a key tool for diagnosing diseases or developing new drugs?
Generating detailed cell maps is now faster than ever. Will AI be the only way to read them?
Does accelerating super-resolution imaging to mere hours compromise the accuracy of what we see inside a cell?

12-Plex DNA-PAINT Enables High-Speed, Nanometer-Precision Multiplexed Super-Resolution Imaging of Nuclear Architecture

Overview

In 2026, Banerjee and colleagues overcame a major limitation in DNA-PAINT imaging by developing twelve speed-optimized DNA sequences, enabling simultaneous super-resolution imaging of up to twelve targets with high precision. Paired with a new analysis pipeline, this breakthrough allowed detailed mapping of nuclear organization, revealing how transcription inhibition disrupts chromatin interactions with nuclear speckles. This advance addressed key challenges in binding kinetics and non-specific background noise, balancing imaging speed and accuracy. Alongside, Combi-PAINT introduced combinatorial barcoding to achieve even higher multiplexing with faster imaging but more complex decoding. Together, these innovations open new possibilities for studying cellular architecture and disease mechanisms at the nanoscale.

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