Is that a phage tail in Fig 4?? 👀

This project was a huge team effort.
The hugest shoutout to @kedmonds.bsky.social for her HEROIC engineering and optimisation (+ birb drawing 🐦🥚)
Also to Hongyu Chen and Dangliang Liu for RNA chemistry, Feng Zhang for fearless leadership, and all the amazing authors who made this possible. (6/n)

RNA stability may limit efficiency. With help from Xiao Wang and her lab, we added chemical modifications to protect donor RNA from exonucleases.
Combined with LNP delivery, this boosted integration efficiency to >80% in multiple human cell lines, all with an RNA system. Which is kinda nuts. (5/n)

The fabulous Grace then took over. She replaced parts of R2Tg RNA with custom sequences — “tricking” the retrotransposon into integrating cargo instead of itself.
She then defined the minimal R2 elements required for integration, leading to a compact, efficient “mini donor”. (4/n)

We found that the R2 retrotransposon from zebra finch (Taeniopygia guttata, “R2Tg”) looked really promising! I had fun playing around with its biochemistry, and solved the cryo-EM structure of it copying its own RNA. We found key features that differ from the more well-studied insect R2. (3/n)

R2 retrotransposons are neat! They're pretty widespread across the animal kingdom, and they propagate by copying themselves into ribosomal DNA, a highly repetitive region of the genome.
This natural system inspired our design: we thought the rDNA could be a good 'safe harbour' for transgenes. (2/n)

If you like transposons...
If you you love genome editing...
Or if you just like random bird animations,

we have the paper for you!

We (@kedmonds.bsky.social et al) are happy to share our work turning a songbird retrotransposon into a genome editing tool. 🐣 (1/n)

TIGR might have some advantages over CRISPR in genome editing (absolutely tiny, no PAM), but more importantly it's just some really neat, mysterious biology. Maybe TIGR is used by phages to fight other viruses? We don't know yet! Many many many questions left.

we recently found some really neat RNA-guided DNA-cutting systems in phages. Despite remarkable similarities to CRISPR systems, including encoding guide RNAs in arrays, they appear entirely evolutionarily distinct (but definitely related to snoRNAs 🤓)
We decided to call them TIGR-Tas systems 🐯

gonna start shamelessly crossposting some of my molecular movies from the Other Place. Starting with my favourite: showing how wacky reverse transcription can defeat viruses. Bonus: some noises 🎹🎻