Thanks to my co-first author, Paul, for being a fantastic scientist to work with, the Balzarotti lab, especially @fbzt.bsky.social for his mentoring across my PhD, the @plaschkalab.bsky.social and I hope you are as excited as we are about the future of combinatorial DNA-PAINT and RNA imaging! 10/10

For the full story, including code to help you create your own fluorogenic DNA-PAINT strands, description of our MINFLUX imaging and improvements, and the full extent of what we were able to learn about mRNA ultrastructure, head to bioRxiv and take a look at the preprint. 9/10

Finally, we used our MINFLUX for 3D mRNP imaging. Dealing with nuclear background required some work, but we managed to obtain high quality images. mRNPs appeared much more complex in shape than what was known before, hinting at inhomogeneous mRNA distributions in mRNPs. 8/10

We combined optimized RNA-FISH with regional Combi-PAINT labelling and super-resolved three mRNAs, MDN1, AHNAK1 and EPRS1. We extracted various parameters, describing mRNP shape and size, obtaining interesting hints of what could be directing mRNA organization in the nucleus. 7/10

We used Combi-PAINT to study mRNA. While we know a lot about the proteins that together with mRNA form messenger ribonucleprotein particles (mRNPs), we know much less about the ultrastructure of mRNA in mRNPs, what influences it, or if it changes upon export from the nucleus. 6/10

The second way uses chains of speed-optimized binding sites, and we show different stoichiometries can be used to encode even more targets. We prove up to 9 targets with the 3 purinic imagers, but we calculate much more can be achieved if you were to use all available strands. 5/10

We did the former via a pipeline that engineers base pair mismatches in silico, followed by testing on DNA origamis. We obtained 3 new fluorogenic imagers, which allow a total of 6 targets to be imaged. We also thoroughly analyzed their kinetics, brightness and fluorogenicity. 4/10

In Combi-PAINT, additional targets are encoded as combinations of individual DNA-PAINT signals, increasing the number of targets exponentially without more washing steps. We show this using both fluorogenic DNA-PAINT strands and conventional, speed-optimized imagers. 3/10

Additionally, there is another excellent work on Combi-PAINT by the @jungmannlab.bsky.social, also on bioRxiv, which I strongly suggest checking out, and shows high-degree Combi-PAINT on proteins! www.biorxiv.org/content/10.6... 2/10