Led by @sharan_janjuha with @AcuitasTx @pardi_lab, our Nat Biomed Eng paper is out 🧬 We use in situ sequencing to read base & prime editing directly in tissues - from mouse brain (AAV) to macaque liver (RNA–LNP)-mapping lobules & redosing. Open access: https://t.co/uhohboUWnb

Excited to share our new protocol in #NatureProtocols! 🧬👨‍💻🎉 A comprehensive guide for using PRIDICT2.0 and ePRIDICT machine learning tools to design efficient #CRISPR-Cas9 prime editing experiments. 🧵 @UZH_Science @schwanklab @krauthammerlab https://t.co/xsIu9WFfHi

Congrats to the entire team and collaborators @uzh @AcuitasTx @KispiZuerich @ETH @upenn. Step-by-step we are getting closer to clinical translation of prime editing to treat metabolic liver diseases!

Have you ever wanted to design protein binders with ease? Today we present 𝑩𝒊𝒏𝒅𝑪𝒓𝒂𝒇𝒕, a user-friendly and open-source pipeline that allows to anyone to create protein binders de novo with high experimental success rates. @befcorreia @sokrypton https://t.co/IPhMFpRgHh

Read the full study at https://t.co/9KuvCzNQlT and our media release at

Many thanks to @UZH_en @UZH_Science @UZH_IPT @ETH_en and @nicopmat @Amina_mollaysa #SaphiraMueller @KisslingLucas @tanjarothgangl @LSchmidheini @p_kulcsar #AhmedAllam and collaborators from the #ManfredKopf and #ToniCathomen labs!

6) To apply TnpBmax in vivo we delivered it together with a PCSK9-targeting ωRNA via AAV9 into mice. This led to a robust PCSK9 knockout in the liver and a reduction in LDL-cholesterol levels

5) ISDra2 TnpB requires a 5'-TTGAT TAM site to bind and cleave DNA. While this makes TnpB highly specific it also restricts its target range. Using structure-guided protein engineering we mutated amino acid 76 to altered the ISDra2 TnpB TAM preference from TTGAT to TTTAT or TTCAT

4) Using this dataset, we developed TEEP, a machine-learning model to predict ωRNA efficiencies and help select potent ωRNAs. The model is freely available via https://t.co/bSXwU9D55e.

3) We noticed that the activity of the TnpB system is strongly influenced by the ωRNA sequence that targets the DNA. This led us to screen over 10,000 target sites in cultured human cells to measure cleavage efficiency in high throughput.

2) To enhance the editing efficiency of ISDra2 TnpB in mammalian cells, we optimized its DNA sequence to match human codon usage and rearranged NLS sequences for nuclear uptake. Our design resulted in a TnpBmax system with a 4.4-fold improvement in editing efficiency.

1) TnpB is an RNA-guided endonuclease encoded on the IS200/IS605 transposon element and evolutionarily related to CRISPR-Cas12 proteins. A recent study from the Siksnys lab showed that ISDra2 TnpB can be programmed to induce targeted DNA breaks in human cells

Excited to share our latest study! Today in @naturemethods the @schwanklab and @krauthammerlab report in @marquark et al. 'Effective genome editing with an enhanced ISDra2 TnpB system and deep learning-predicted ωRNAs' (1/6) https://t.co/lqDc5Kn2Xw

Nature research paper: Structural mechanism of bridge RNA-guided recombination

Our first in vivo primary NK screen that discovered new NK cellular checkpoints. Kudos for team for their 5 years of work. https://t.co/d0e3Bguzou @YaleGenetics @YaleMed @YaleWestCampus @YaleCancer @YaleData

Our paper exploring the effect of chromatin on prime editing and diverse pegRNA designs was published today! 👨‍💻🧬🎉 https://t.co/hoygYAHbPH https://t.co/xvSlhTJvNV @UZH_Science @NatureBiotech @schwanklab @krauthammerlab @bvansteensellab 🧵

If you want to know the outcome of your prime editing experiment before you even conducted the experiment, visit https://t.co/tEG0mcEIEo Congrats to Nicolas and many thanks to all collaborators @krauthammerlab @bvansteensellab

Join us at the Latsis Symposium on Genome and Transcriptome Engineering organized by @MartinJinek @randall_platt @jcornlab and @schwanklab, with lots of great speakers from academia and industry! 🧬 #Zurich #Switzerland June 13-14. Register at: https://t.co/Ch8w6g2pqt

🌟New Postdoc opportunity🌟 for developing machine learning methods in biomedicine and healthcare research is open in our lab! Apply 👉 https://t.co/IkVhBsKaK1 Please RT and share widely! #MachineLearning #healthcare #postdoc #ArtificialIntelligence #biomedicine #bioinformatics

Join me at the Latsis Symposium on Genome Engineering #Zurich #switzerland June 13-14! Register now at https://t.co/O1IlrEpyuk @TreutleinLab @BKleinstiver @DiMiccoLab @skathire @janiceschen @cgersbach @CejkaLab @TeresaDavoli3 @jsvanleeuwen @CIBIOcrispr @obenaufa @priscaliberali