Doudna Lab

🚀 New preprint! @jacobsenucla.bsky.social x @doudna-lab.bsky.social collaboration: High-activity TnpB (Ymu1-WFR) + a multi-gRNA system in TRV enables heritable, tissue-culture-free multiplex editing in plants. Big potential for plant biotech 🧬🌾🌱
doi.org/10.64898/202...

How do the ancestors of CRISPR-Cas unwind DNA and how can this lead to better genome editing? With our collaboration between @doudna-lab.bsky.social x @jacobsenucla.bsky.social x Zev Bryant's lab x @savagecatsonly.bsky.social we've uncovered the secrets behind TnpB's dynamics!

Victoria Gray

Check out the latest episode of Rewriting the Code, featuring Jennifer Doudna and #SickleCell patient pioneer Victoria Gray who was cured with a #CRISPR-based treatment in a groundbreaking clinical trial: https://ow.ly/t6FY50XVNO7

Targeted delivery of genome editors in vivo - @doudna-lab.bsky.social @innovativegenomics.bsky.social go.nature.com/4qKp6Tb

Stepwise DNA unwinding gates TnpB genome-editing activity TnpB is a compact RNA-guided endonuclease and evolutionary ancestor of CRISPR-Cas12 that offers a promising platform for genome engineering. However, the genome-editing activity of TnpBs remains limit...

New preprint 👉Doudna x Bryant x Jacobsen x Savage collaboration!
Work led by @zehanzhou.bsky.social, I. Saffarian-Deemyad, @honglue.bsky.social, T. Weiss
We dissect how stepwise DNA unwinding gates TnpB genome editing, revealing how unwound DNA states enhance cleavage
www.biorxiv.org/content/10.6...

Fig. 5. Phylogenetic distribution of VchCAST activator and inhibitor genes. The phylogenetic distribution of 11 E. coli regulatory genes was mapped across 80,789 representative bacterial genomes from 92 phyla in Genome Taxonomy Database, release 214.0 (GTDB version 214.0) (72, 73), with at least 10 members. Homologs were identified using AnnoTree (60) and confirmed with the eggNOG database (70).

New in Science Magazine Science Advances from the Doudna Lab, Rubin Lab and Cress Lab —Identification of proteins influencing #CRISPR-associated #transposases for enhanced #GenomeEditing. Read here: https://ow.ly/U0s450XS82n

During my postdoc in @therubinlab.bsky.social, @leosong.bsky.social and I aimed to make CRISPR-associated transposons more efficient for editing bacteria.

Couldn’t have done it w/o a CAST of characters at IGI and beyond @innovativegenomics.bsky.social, @cresslab.bsky.social, @doudna-lab.bsky.social

Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap - Nature Chemical Biology A multiscale photoproximity labeling proteomics workflow captures dynamic neighborhoods of extracellular and intracellular epidermal growth factor (EGF) receptor interactomes during early, middle and late signaling upon activation by EGF.

🎺New paper alert🎺 Out now in Nature Chemical Biology from IGI's Jennifer Doudna (Doudna Lab) and collaborators: Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap

Read here: https://ow.ly/izGo50XAkog

Excited to share our work designing genome editors with machine learning! 🧬💻 Huge thanks to
@petrskopintsev.bsky.social @isabelesain.bsky.social @doudna-lab.bsky.social and all co-authors. Check out the thread for a summary of what we found 👇

Viral enzymes degrade to evade Across all domains of life, immune systems rely on nucleotide-based signaling molecules to activate defense responses. In a recent Cell Host & Microbe study, Doherty, Nomburg, and colleagues identify ...

A very nice Preview of our work in
@cp-cellhostmicrobe.bsky.social
this morning from Chrishan Fernando & Nicole D. Marino! www.cell.com/cell-host-mi...

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Congrats to IGI's Jill Banfield, Jennifer Doudna, Mary Firestone, Patrick Hsu, Alex Marson, Kris Niyogi, Eva Nogales, Dan Nomura, and Jennifer Puck — each is on Clarivate's Highly Cited Researchers 2025 list for ranking in the top 1% in their field by citations!

Excited to share our first work on protein design! Huge thanks to the entire team, and especially to Bel, Evan, to the Doudna, Jacobsen, Cate, Banfield labs, all co-authors, and my D-lab mates! 💫

First co-led work from the Doudna lab 🤜🤛
We designed minimal RNA-guided nucleases with AI, and even did Cryo-EM during an earthquake (!) Huge honor working with @petrskopintsev.bsky.social, @evandeturk.bsky.social, Jennifer Doudna and co-authors, everyone at D-Lab and @innovativegenomics.bsky.social

🧵4/4 We solved the first experimental structure of an AI-designed RNA-guided nuclease, which revealed new protein-nucleic acid contacts across conformational states.

🔗 See our preprint:
www.biorxiv.org/content/10.6...

🧵3/4 We assessed activity using a high-throughput bacterial assay, followed by editing the human and plant genomes 🧫🌱

🧵2/4 By coupling inverse folding with evolutionary information, we generated highly active and diverse variants with a high design success rate ⚙️

✨New preprint!

🧵1/4 Excited to share our work on AI-guided design of minimal RNA-guided nucleases. Amazing work by @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social et al!
Multi-lab collaboration @banfieldlab.bsky.social @jhdcate.bsky.social @jacobsenucla.bsky.social🧬

🔗👇

Structure and evolution-guided design of minimal RNA-guided nucleases The design of RNA-guided nucleases with properties not limited by evolution can expand programmable genome editing capabilities. However, generating diverse multi-domain proteins with robust enzymatic...

🧵4/4 We solved the first experimental structure of an AI-designed RNA-guided nuclease, which revealed new protein-nucleic acid contacts across conformational states.

🔗 See our preprint at the link below!
www.biorxiv.org/content/10.6...

🧵3/4 We assessed activity using a high-throughput bacterial assay, followed by editing the human and plant genomes! 🧫🌱

🧵2/4 By coupling inverse folding with evolutionary information, we generated highly active and diverse variants with a high design success rate ⚙️

Career update: I'm happy to say that I've accepted a postdoc position at UC Berkeley at @innovativegenomics.bsky.social in Jennifer Doudna's lab! I'm looking forward to this exciting new chapter of my scientific career!

We're excited to share our lab's first lead paper!

We developed OriGen, a language model trained to generate plasmid origins of replication. 🔄🦠

The model generates sequences that are significantly different from wild type origins and, remarkably, they allow for replication in vivo.

Read it here ⬇️

New Method Uncovers How Viruses Evade Immune Responses — and How We Might Fight Back Explore how viruses evade immune responses by developing enzymes that disrupt molecular alarm signals in host cells.

1/2 New from co-first authors @erinedoherty.bsky.social and @jnoms.bsky.social of the @doudna-lab.bsky.social — Bacteria fight off viruses using tiny molecular “alarm signals” made of nucleotides. To survive, viruses must find ways to shut these signals down.

My lab is hiring postdocs! We combine AI, protein structure prediction and comparison, and high-throughput virology to study the virus-host conflict.

You can read more about my lab's research here: jasonnomburg.com/research/

Apply here to join us in lovely Vienna! aithyra.onlyfy.jobs/job/0khkxp82

So happy to see this work out! Was such a pleasure to co-lead this effort with Erin. Do you like viral immune evasion, and using protein structure to study immune antagonists? Give it a read!

Divergent viral phosphodiesterases for immune signaling evasion Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to …

Work I co-led with @jnoms.bsky.social is now online at
@cp-cellhostmicrobe.bsky.social ! We revealed a previously unrealized diversity of viral immune-evasion proteins that selectively destroy different cyclic nucleotide signals used in bacterial immunity.

www.sciencedirect.com/science/arti...

Now online at @cp-cellhostmicrobe.bsky.social from co-first authors @erinedoherty.bsky.social & @jnoms.bsky.social

Recurrent acquisition of nuclease-protease pairs in antiviral immunity Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin-like protease repeatedly acquired by multiple, ...

New in Science Magazine from the Doudna Lab and first author Owen Tuck: Recurrent acquisition of nuclease-protease pairs in antiviral immunity. Read here: https://ow.ly/pIWQ50XtEtM

New from the @doudna-lab.bsky.social and first author @owentuck.bsky.social!

Recurrent acquisition of nuclease-protease pairs in antiviral immunity Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin...

Our nuclease-protease story is out! We explored a fascinating case of coevolution and modularity in prokaryotic immune systems: www.science.org/doi/10.1126/...

Thanks to wonderful coauthors/collaborators/friends, the whole @doudna-lab.bsky.social and everyone at @innovativegenomics.bsky.social