Spatial Proofreading Amplification of in situ Transcript and Protein Signals

Tischbirek, C. H.; Colon, K. L.; Lobbia, S.; Cronin, C. J.; Cai, L.

doi:10.1101/2025.06.11.659176

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bioRxiv · 10.1101/2025.06.11.659176

Spatial Proofreading Amplification of in situ Transcript and Protein Signals

Tischbirek, C. H.·Colon, K. L.·Lobbia, S.·Cronin, C. J.·Cai, L.

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Abstract

Spatial transcriptomics experiments greatly benefit from brighter signals that improve detection efficiency and shorten imaging times. Here, we introduce a new enzyme-free signal amplification method inspired by the kinetic proofreading principle, in which short oligonucleotide probes are iteratively deposited at their target site and covalently photo-crosslinked to the cell, forming highly stable DNA assemblies. The method results in more than 500-fold signal amplification and supports multiplex readout capabilities.

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Tischbirek, C. H., Colon, K. L., Lobbia, S., Cronin, C. J., Cai, L.. 2025-06-15. Spatial Proofreading Amplification of in situ Transcript and Protein Signals. https://doi.org/10.1101/2025.06.11.659176

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