Jonathan Gootenberg @jgooten Twitter profile | Pikagi

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Jonathan Gootenberg

@jgooten

4,662

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1,775

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Pull apart the double helix like a wishbone || Ars longa, tweeta brevis

Cambridge, MA

https://t.co/3bq3AMInjP

Joined December 2012

Don't wanna be here? Send us removal request.

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@jgooten

Jonathan Gootenberg

12 days

Directed evolution won a Nobel prize by unlocking new protein functions How can we augment evolution to engineer proteins 10-100 times better? By using large language models! Here we present EVOLVEpro, an LLM for accelerated protein evolution 1/

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Rapid protein evolution by few-shot learning with a protein language model

Directed evolution of proteins is critical for applications in basic biological research, therapeutics, diagnostics, and sustainability. However, directed evolution methods are labor intensive,...

www.biorxiv.org

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@jgooten

Jonathan Gootenberg

2 years

CRISPR-based genome editing has been transformative, but insertion of large sequences requires DNA damage machinery How can we efficiency place DNA cargos anywhere in the genome? Today we report on PASTE, out in @NatureBiotech w/ @omarabudayyeh @MIT 1/🦃

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@jgooten

Jonathan Gootenberg

1 year

CRISPR nucleases have been transformative. What if there were similar RNA-programmed nucleases in eukaryotic genomes? Turns out, they are abundant (>3500) and functional! Today we share findings on novel RNA-guided DNA nucleases in eukaryotes. 1/14

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Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses

TnpB proteins are RNA-guided nucleases that are broadly associated with IS200/605 family transposons in prokaryotes. TnpB homologs, named Fanzors, have been detected in genomes of some eukaryotes and...

www.biorxiv.org

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@jgooten

Jonathan Gootenberg

2 years

You know CRISPR complexes can cut DNA/RNA….what if some of them cleaved proteins too? Today in @biorxivpreprint , we (+ @omarabudayyeh @hnisimasu ) continue our study of Cas7-11 and type III-E systems, revealing a new triggered protease function 1/6

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RNA-triggered protein cleavage and cell death by the RNA-guided type III-E CRISPR-Cas nuclease-pr...

The type III-E Cas7-11 effector nuclease forms a complex with a CRISPR RNA (crRNA) and the putative caspase-like protease Csx29, catalyzes crRNA-guided target RNA cleavage, and has been used for RNA...

www.biorxiv.org

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@jgooten

Jonathan Gootenberg

11 months

Me when my gel fails

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@jgooten

Jonathan Gootenberg

3 years

Genome editing owes a huge debt to genome sequencing With efforts like @humancellatlas , we’re sequencing cells like mad. What is the "Cas9" of single cell? With @omarabudayyeh @insitubiology : RADARS, for programmable cell-specific sensing/expression 🧵👇

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Programmable eukaryotic protein expression with RNA sensors

The diversity of cell types and states can be scalably measured and defined by expressed RNA transcripts. However, approaches to programmably sense and respond to the presence of specific RNAs within...

www.biorxiv.org

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@jgooten

Jonathan Gootenberg

3 years

New preprint! How do you insert large genes efficiently + programmatically? CRISPR-based methods are programmable, integrases are efficient. Why not combine them? PASTE places short (~45bp) integrase landing sites that serve as beacons for insertion (up to 36kb)! @omarabudayyeh

@biorxivpreprint

bioRxiv

@biorxivpreprint

3 years

Drag-and-drop genome insertion without DNA cleavage with CRISPR-directed integrases #bioRxiv

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@jgooten

Jonathan Gootenberg

6 months

Genome editing has revolutionized the treatment of rare disease. What if we could put any change into RNA safely and reversibly? Today we (+ @omarabudayyeh ) debut PRECISE, allowing for RNA edits, deletions, and insertions from 1 to >1,000nt 🧵 1/x

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@jgooten

Jonathan Gootenberg

28 days

The AbuGoot lab is moving to HMS! Excited to be a faculty member at @BIDMChealth and @harvardmed . Interested in programmable biology, including nucleic acid editing, aging , and ML-driven protein/cell engineering? We're hiring - join us in pioneering biotech frontiers

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@jgooten

Jonathan Gootenberg

3 years

Our story on the newest CRISPR effector for RNA targeting, Cas7-11, is out now in @nature ! So what’s the deal with the newest member of the CRISPR club? (surprisingly not an ad for @7eleven ) @omarabudayyeh . Read the paper here . 1/n

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@jgooten

Jonathan Gootenberg

10 months

Can Eukaryotic RNA programmable DNA nucleases be used for efficient mammalian genome editing? Turns out they can! An update on our work on Fanzors (f.k.a Hermes) nucleases, now out! 1/6

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Programmable RNA-guided DNA endonucleases are widespread in eukaryotes and their viruses

Fanzor is an RNA-guided DNA endonuclease widespread in eukaryotes and their viruses.

www.science.org

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@jgooten

Jonathan Gootenberg

3 years

How can #CRISPR tools be applied to help diagnose and track disease? @omarabudayyeh and I cover how quickly the field has developed-with two(!) FDA-authorized products-in @ScienceMagazine . Sure there will be many more breakthroughs in CRISPRdx to come!

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@jgooten

Jonathan Gootenberg

2 years

How can we apply new structural insights to engineer the next generation of RNA-targeting CRISPR tools? Today, with @omarabudayyeh @hnisimasu , we reveal the structure of the Cas7-11 RNA-targeting nuclease 1/7

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@jgooten

Jonathan Gootenberg

8 months

With the the fantastic progress in recent weeks with Casgevy, it's clear a new wave of medicines will transform patient lives. @omarabudayyeh and I founded @Tome_bio to answer the question: What will the next generation of genomic medicines be? 🧵

@Tome_bio

Tome Biosciences

8 months

Tome Biosciences emerges from stealth with $200M+ Series B funding to advance genetic medicine with the ability to insert large DNA segments wherever they’re programmed to go. Read the press release here: #TomeBio #CRISPR #LastChapterofGenomicMedicine

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@jgooten

Jonathan Gootenberg

7 months

How can we make any change in the genome, regardless of size? Today, @Tome_bio announces the acquisition of Replace Therapeutics. Together, PASTE and Replace allow edits both big and small, paving the way for new gene and cell therapies. Excited to bring these to patients!

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@jgooten

Jonathan Gootenberg

3 years

The AbuGoot lab at @mcgovernmit @MIT @ScienceMIT is hiring research associates! Join me and @omarabudayyeh in developing next-generation molecular tools for cellular engineering. See more here:

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@jgooten

Jonathan Gootenberg

7 months

Want to work at the cutting edge of biomedical innovation? Join the Abudayyeh-Gootenberg Lab as a lab manager! A chance to be part of a team creating molecular technologies and AI for gene editing, RNA therapies, aging, and rejuvenation. Apply here:

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@jgooten

Jonathan Gootenberg

6 months

Check out our new review in @NatRevMCB on the landscape of CRISPR tools. Happy to see that the overview of clinical trials is already outdated with approval of Casgevy! Congrats to authors @lukas_villiger @JuliaJoung @omarabudayyeh @LukeKoblan @JswLab

@lukas_villiger

Lukas Villiger

@lukas_villiger

6 months

Impossible to do the field justice on a few pages but we ( @jgooten @omarabudayyeh @jsw @JuliaJoung @LukeKoblan ) tried our best to give an overview of current CRISPR technologies in @NatRevMCB

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@jgooten

Jonathan Gootenberg

5 months

Excited to move forward the next generation of CRISPR-based diagnostics and medicines with @jrkelly

@Ginkgo

Ginkgo Bioworks

5 months

We’re also thrilled to announce our acquisition of Proof Diagnostics! Proof was founded by gene editing pioneer Dr. @zhangf of the Broad Institute of MIT and Harvard, Drs. @omarabudayyeh and @jgooten of the @mcgovernmit , and Sid Shenai to develop a low cost, rapid, easy-to-use,

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@jgooten

Jonathan Gootenberg

3 years

We’re hiring -- looking for postdocs to work on a new suite of molecular tools for cellular engineering! Genome engineering as a field is just scratching the surface of what we’ll be able to do cells soon... With @omarabudayyeh Apply below:

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@jgooten

Jonathan Gootenberg

4 years

So proud of @rahulkdhanda and the @Sherlock_Bio team for making history. Glad that we have the opportunity to work with you! @omarabudayyeh @zhangf

@Sherlock_Bio

Sherlock Biosciences

4 years

#BREAKINGNEWS Sherlock Biosciences makes history for first ever #FDA authorized use of #CRISPR technology. Emergency Use Authorization granted for test kits which use the SHERLOCK™ CRISPR-based method to rapidly identify the virus that causes #COVID19

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@jgooten

Jonathan Gootenberg

5 years

Ever wanted to do CRISPR diagnostics but didn't know where to start? Check out our new protocol!

@NatureProtocols

Nature Protocols

@NatureProtocols

5 years

#FreeAccessProtocol this week: Heard about SHERLOCK yet? Detect any #DNA or #RNA with this #CRISPR -based diagnostic platform using protocol from Feng Zhang @zhangf

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@jgooten

Jonathan Gootenberg

2 years

How can we use RNA-programmable proteases to sense RNA in mammalian cells? Our updated manuscript with @omarabudayyeh @hnisimasu is out today @ScienceMagazine , describing the structure, mechanism, and application of a CRISPR-guided protease

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RNA-triggered protein cleavage and cell growth arrest by the type III-E CRISPR nuclease-protease

The type III-E CRISPR-Cas7-11–Csx29 effector is an RNA-dependent nuclease protease that can be applied for RNA sensing.

www.science.org

@jgooten

Jonathan Gootenberg

2 years

You know CRISPR complexes can cut DNA/RNA….what if some of them cleaved proteins too? Today in @biorxivpreprint , we (+ @omarabudayyeh @hnisimasu ) continue our study of Cas7-11 and type III-E systems, revealing a new triggered protease function 1/6

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@jgooten

Jonathan Gootenberg

9 months

Open house alert! Reminder that the AbuGoot lab is hosting a session on **Monday** for graduate students at @MIT @Harvard @harvardmed Come get pizza and hear about the next generation of technologies we're building and using to treat disease. RSVP here:

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AbuGoot Lab rotation student open house RSVP

The Abudayyeh-Gootenberg Lab (abugootlab.org) will be having an open house for prospective rotation students on November 20th from 5:30-7pm. We’ll have presentations from current lab members about...

docs.google.com

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@jgooten

Jonathan Gootenberg

2 years

The updated version of our RADARS manuscript is out at @NatureBiotech , including more optimizations on the sensor and a thorough dive into the effects the technology has on the cell. See more in @idmjky ’s tweetorial below!

@idmjky

Kaiyi Jiang

2 years

Excited to share that our latest RADARS story is finally out in Nature Biotech. Since the last arXiv, we extensively engineered our sensor and now present RADARSv2 with better safety profile and enhanced sensitivity to detect genes as low as 13 TPM.

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@jgooten

Jonathan Gootenberg

5 years

Looking to learn about the latest developments in genome editing and CRISPR tools? The Zhang lab is hosting its seventh annual genome engineering workshop, which will be held May 19th and 20th at the Broad Institute in Cambridge, MA. Check it out at !

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@jgooten

Jonathan Gootenberg

5 years

Looking to join our new team focused on molecular tool development and aging? Apply below 👇

@omarabudayyeh

Omar Abudayyeh

5 years

The Abudayyeh-Gootenberg lab () has open positions. We're molecular engineers working on novel tools for gene therapy and aging 🧬🧪 Look forward to hearing from you! Technical associate: Postdoctoral fellow:

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@jgooten

Jonathan Gootenberg

3 years

Looking to use Cas7-11? Plasmids are on @Addgene ! 👇

@Addgene

Addgene

3 years

pDF0229 DisCas7-11 bacterial expression vector with golden gate site for guides Depositor: Omar Abudayyeh @omarabudayyeh Purpose: Encodes DisCas7-11 protein alone with a golden gate site for spacer cloning

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@jgooten

Jonathan Gootenberg

3 years

...I will accomplish the goals outlined in this proposal with 5 synergistic, but independent aims: 1. Denial 2. Anger 3. Bargaining 4. Depression 5. Acceptance

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@jgooten

Jonathan Gootenberg

11 months

@genomerambler Hunch: 70% of the alien genome is Illumina adapters.

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@jgooten

Jonathan Gootenberg

4 years

Cool work from @stanleyqilab using Cas13d for targeting RNA viruses! (As with work from @PardisSabeti , @cambearon , @CatherineFreije on CARVER , delivery is an open question)

@biorxivpreprint

bioRxiv

@biorxivpreprint

4 years

Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza #bioRxiv

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@jgooten

Jonathan Gootenberg

2 years

Amazing gem from #cshlcrispr22 : “Where there is a will, there is a wei” - @wchenomics

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@jgooten

Jonathan Gootenberg

4 years

@omarabudayyeh @zhangf STOPCovid is a simple workflow with no extraction step, a single incubation, minimal user handling, and paper strip readout. NP swabs or saliva work. The test can sense as little as 100 viruses/sample with 97% sensitivity and 100% specificity, and can even run in a sous vide. 2/4

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@jgooten

Jonathan Gootenberg

2 years

What does the phrase “molecular tool” evoke for you?

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@jgooten

Jonathan Gootenberg

2 years

To help support adoption of the technology and innovation on the platform, we've put the plasmids up on @Addgene , and you can get them here: 9/🦃

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@jgooten

Jonathan Gootenberg

6 years

@omarabudayyeh defending his thesis!

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@jgooten

Jonathan Gootenberg

2 years

Well now we at least know that if plasmids don't work out, Addgene can at least pivot to a pun repository.

@Addgene

Addgene

2 years

Thanks to @omarabudayyeh and @jgooten for depositing their two exciting new CRISPR tools, Cas7-11 and PASTE, with us! We promise we're done with the puns. (for now.)

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@jgooten

Jonathan Gootenberg

3 years

Also be sure to check out @omarabudayyeh 's tweetorial for the key Austin Powers reference

@omarabudayyeh

Omar Abudayyeh

3 years

Today we report in @biorxiv programmable RNA sensors that express any protein gated on specific RNAs in a cell. Much like gene sequencing necessitated gene editing tools, we answer “What is the Cas9 of single cells?” 🧵👇🏼w @jgooten & @insitubiology 1/17

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@jgooten

Jonathan Gootenberg

3 years

Catch @omarabudayyeh and me chatting with @aurmanARK @ARKInvest about what's next in genome/transcriptome/cell editing and engineering!

@aurmanARK

Ali Urman

3 years

**Alert** looking forward to a very exciting evening tomorrow talking to the incredible Drs Jonathan Gootenberg and Omar Abudayyeh @jgooten @omarabudayyeh @ARKInvest

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@jgooten

Jonathan Gootenberg

2 years

Get your plasmids on @addgene

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New CRISPR Tools: Cas7-11 and PASTE

Two new CRISPR tools from the Abudayyeh-Gootenberg lab are now available at Addgene: Cas7/11 and PASTE.

blog.addgene.org

@Gabrus

gabrus🚽

2 years

we love PASTE!

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@jgooten

Jonathan Gootenberg

5 years

Award for most enthusiastic bioRxiv title goes to

@biorxivpreprint

bioRxiv

@biorxivpreprint

5 years

DO THESE CRAYFISH MAKE ME LOOK FAT? BODY CONDITION CORRELATES TO PREY ABUNDANCE IN THREE HELLBENDER (CRYPTOBRANCHUS ALLEGANIENSIS) POPULATIONS #bioRxiv

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@jgooten

Jonathan Gootenberg

5 years

Standing room only for @corinnefmaurice ’s talk on microbiome-phage interactions in child stunting at #ECCMID2019

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@jgooten

Jonathan Gootenberg

3 years

Mandatory reading

@TheOnion

The Onion

3 years

The Onion’s Guide To CRISPR

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@jgooten

Jonathan Gootenberg

2 years

Using Cas9, the reverse transcriptase, and the integrase simultaneously, we show that we can install cargo of up to 36kb (this was just the largest we tried--we actually don't know the upper limit) 6/🦃

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@jgooten

Jonathan Gootenberg

2 years

We put on our natural diversity mining hats, and scoured bacterial genomes and metagenomes for new integrases, finding >25,000 new family members. Sampling of this diversity, we show many of these new integrases are both functional in human cells and compatible with PASTE 8/🦃

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@jgooten

Jonathan Gootenberg

2 years

We've seen a fantastic array of CRISPR-based tools, including base and prime editing, combining the programmable nature of CRISPR effectors with deaminases, reverse transcriptases, etc for efficient installation of small edits. How can we do the same for large edits? 3/🦃

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@jgooten

Jonathan Gootenberg

5 years

Epitranscriptomics with Cas13!

@biorxivpreprint

bioRxiv

@biorxivpreprint

5 years

Targeted mRNA demethylation using an engineered dCas13b-ALKBH5 fusion protein #bioRxiv

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@jgooten

Jonathan Gootenberg

3 years

Like molecular tool discovery/engineering or random GIFs? We’re hiring, come work with us! (They didn't let us keep the sushi boat, unfortunately) 14/14

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@jgooten

Jonathan Gootenberg

4 years

@omarabudayyeh @zhangf An amazing effort with @zhangf , @omarabudayyeh , @JuliaJoung , @LadhaAlim , MSegel, MSaito, RMacrae, and EBlackwell who worked endlessly on COVID-19 testing. Huge thanks to support inclu @McGovernMIT , @broadinstitute , @NIH , @PJMFnd , @NEBiolabs , @Quintara_Bio , @Synthego , @MassCPR .4/4

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@jgooten

Jonathan Gootenberg

1 year

More broadly, HERMES are yet another example of how we can still find novel biological tools, both in prokaryotes and eukaryotes, and that we never know what we’ll find when we start searching! 14/14

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@jgooten

Jonathan Gootenberg

2 years

myeloid gf, lymphoid bf

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@jgooten

Jonathan Gootenberg

4 years

@omarabudayyeh @NEJM Building off of our preprint where we used Cas12b and LAMP as a one-pot formula for CRISPR diagnostics, we’ve added a portable concentration with magnetic beads (50x sensitivity boost), as well as an in-line human control using an additional fluor channel

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@jgooten

Jonathan Gootenberg

2 years

Integrases are a great natural approach for genome integration (and another tool from the ever-waging battle of bacteria+phages) that can insert >50kb at specific sites! However, their sequence preferences are strict. Previous efforts fusing with Cas9 have had low efficiency 4/🦃

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@jgooten

Jonathan Gootenberg

28 days

@omarabudayyeh and I are seeking passionate researchers for genetic disease interventions, anti-aging tech, and AI-driven bioengineering. Grateful for mentorship from @zhangf , Aviv Regev @broadinstitute , and Bob Desimone @mcgovernmit . Let's shape the future of biology together!

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@jgooten

Jonathan Gootenberg

2 years

We tackled the approach by breaking it down into two steps, occuring at the same time--PASTE: 1) Place the integrase using programmable genome editing (in the publication, we use prime editing from @davidrliu 2)Use the integrase to insert the cargo 5/🦃

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@jgooten

Jonathan Gootenberg

5 years

Ah...so that’s what MIT stands for.

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@jgooten

Jonathan Gootenberg

2 years

And given today, we're thankful for the great team, including co-first authors Matt Yarnall, Eleonora I. Ioannidi, Cian Schmitt-Ulms, @RohanKrajeski Justin Lim, @91_naynay , @lukas_villiger , @KevinHoldenSF , @lfoquet and many other collaborators! 11/gobble

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@jgooten

Jonathan Gootenberg

4 years

This actually blew my mind. Makes you wonder what current papers are going to have cross relevance in 12 years...

@ESontheimerLab

ErikSontheimerLab

@ESontheimerLab

4 years

Whoa — the two papers were not only in the same issue, they were back to back! Through the lens of hindsight and the current trailblazing SCD/CRISPR clinical trials, that’s a truly providential alignment. Amazing indeed — thank you for flagging it!

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Jonathan Gootenberg

3 years

We hope that RADARS will be useful to the community for basic research, diagnostics, and therapeutics. @omarabudayyeh are actively growing our team to apply across multiple applications – reach out if you’d like to be a part of it! 12/13

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@jgooten

Jonathan Gootenberg

3 years

Thanks to co-authors including Eleonora Ioannidi, Matt Yarnall, Cian Schmitt-Ulms, Rohan Krajeski, Justin Lim, Lukas Villiger( @lukas_villiger ), Wenyuan Zhou ( @91_naynay ), Kaiyi Jiang and collaboration from @KevinHoldenSF @Synthego and @idtdna

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@jgooten

Jonathan Gootenberg

2 years

Efficient, multiplexed integration of DNA into the genome is necessary to unlock multiple threads in basic and translational biology, including 1) Knock-in to tag genes to study function 2) Creation of new cell therapies 3) Treatment of genetic disease 2/🦃

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@jgooten

Jonathan Gootenberg

2 years

For the creation of cell therapies, we show that the system can be tweaked for multiplexing. By engineering the integrase attachment sites, we demonstrate parallel insertion of three cargo at three different sites (with no crosstalk). 7/🦃

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@jgooten

Jonathan Gootenberg

2 years

This flexibility means we can install complete replacement genes at their natural sites, instead of creating-variant specific treatments! 7/🦃

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@jgooten

Jonathan Gootenberg

3 years

RADARS flips this around: instead of guide editing the transcript, what if the transcript edited the guide? Put a stop codon in the guide, blocking expression of a “payload” gene downstream. When the transcript is present, binding->guide editing->viola, payload is expressed 4/13

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@jgooten

Jonathan Gootenberg

3 years

@elkingtonxy @omarabudayyeh Thanks so much! You forgot the most accurate duo comparison though.

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@jgooten

Jonathan Gootenberg

4 months

And since to look at things in bloom Fifty springs are little room, About the woodlands I will go To see the cherry hung with snow. -A. E. Housman

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@jgooten

Jonathan Gootenberg

2 years

If you’re interested in applications of Cas7-11, for either RNA cleavage or protein cleavage, or just want to discover and build cool molecular tools, the AbuGoot lab is hiring. Come join! 6/6

Join us! | AbuGoot Lab

www.abugootlab.org

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@jgooten

Jonathan Gootenberg

3 years

Looking forward to chatting with @pdhsu @omarabudayyeh @HishamYous about CRISPR and beyond. Shoot your shot for favorite nuclease

@medtechclub

MedTech Club

3 years

“Future of gene editing &biotech w Brkly/MIT CRISPR pioneers” with @HishamYous , @jgooten , @pdhsu , @omarabudayyeh , and MedTech. Sunday, Feb 21 at 18:00 EST on @joinclubhouse !

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@jgooten

Jonathan Gootenberg

3 years

RADARS can be used for more than just sensing – by swapping out the payload for a caspase, we can do transcript-dependent cell killing. Ever wanted to “knock out” a cell in your population as a perturbation? Now you can! (Also, tons of therapeutic applications here) 8/13

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@jgooten

Jonathan Gootenberg

1 year

See @omarabudayyeh 's tweetorial for a deeper dive into the transposon biology!

@omarabudayyeh

Omar Abudayyeh

1 year

Programmable biology is powerful. RNA-guided Argonautes enabled RNAi and CRISPR transformed gene editing. Ever wondered if other examples of RNA-guided biology exist? Today in @biorxivpreprint , we report on novel RNA-guided DNA nucleases in eukaryotes🧵👇🏼

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@jgooten

Jonathan Gootenberg

3 years

In case the bioRxiv PDF isn't working --

PASTE Manuscript.pdf

drive.google.com

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@jgooten

Jonathan Gootenberg

2 years

Since we posted the original pre-print in 2021 (alongside Twin-PE from @davidrliu ), we've had a great influx of requests, so don't hesitate to reach out 10/🦃

@jgooten

Jonathan Gootenberg

3 years

New preprint! How do you insert large genes efficiently + programmatically? CRISPR-based methods are programmable, integrases are efficient. Why not combine them? PASTE places short (~45bp) integrase landing sites that serve as beacons for insertion (up to 36kb)! @omarabudayyeh

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@jgooten

Jonathan Gootenberg

2 years

Not just a cool signaling cascade, this RNA-triggered protease has applications in vitro and in vivo…stay tuned! This great team effort was possible due to co-authors incl. @omarabudayyeh @hnisimasu Kazuki Kato, Sae Okazaki, @idmjky , Cian Schmitt-Ulms, and @91_naynay 5/6

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Jonathan Gootenberg

3 years

However, we quickly found out that Cas13 wasn’t exactly the “Cas9 for RNA” -- it had a property called the collateral effect, which meant that once it found its target and was activated, it would chew up other RNA species in solution. Not great for cells. 4/n

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Jonathan Gootenberg

2 years

To take PASTE all the way, we decided to go in vivo, testing the system in humanized mouse models, using adenoviral delivery to integrate into hepatocytes. We're excited to see how the technology is applied both in cells and in animals! 8/🦃

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Jonathan Gootenberg

3 years

Searching through and expanding diversity, we found many additional examples of these proteins, including a subclass that Eugene and Kira found weren’t actually 7-11 at all, but instead an evolutionary intermediate during the consolidation of the single-protein system! 8/n

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Jonathan Gootenberg

3 years

One morning, as Gregor Samsa was waking up from anxious dreams, he discovered that in bed he had been changed into a cat

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Jonathan Gootenberg

1 year

This work was a huge team effort from @omarabudayyeh , @eugene_koonin , Natalya Yutin, Kaiyi Jiang @idmjky , Justin Lim, Samantha Sgrizzi, Michael Trinh @MichaelTrinh18 , and Alisan Kayabolen @alisankayabolen 2/14

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Jonathan Gootenberg

3 years

This work wouldn't have been possible without support from Impetus Grants @MartinBJensen , NIH @NIBIBgov @genome_gov , K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics, G. Harold & Leila Y. Mathers Charitable Foundation, @CF_Foundation , and all our other supporters!

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Jonathan Gootenberg

4 years

@omarabudayyeh @NEJM @jeffhuber This work was the product of a great collaboration, including @zhangf , @juliajoung , @LadhaAlim , Alex Greninger, Keith Jerome, Deborah Hung, @brucedwalkermd , @drjli , and many others!

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Jonathan Gootenberg

5 years

@psuvafan007 Our originals, REJECT and RETRACT, didn’t test too well.

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Jonathan Gootenberg

5 years

Plz make anti CRISPR CRISPR club @joeBondyDenomy

@philfrankino

Phil Frankino, PhD (he/him)

5 years

So this happened today.. Matching lab hoodies! Guess what we study? 😎 @dillinlab @berkeleyMCB #aging #teambonding #antiagingagingclub

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Jonathan Gootenberg

6 months

PRECISE was a labor of love, coming from co-first authors Cian Schmitt-Ulms and @alisankayabolen along with with Marcos Manero Carranza, @91_naynay , Keira Donnelly, Sabrina Pia Nuccio, Kazuki Kato, and Hiroshi Nishimasu @hnisimasu . Congrats to all team members! 7/7

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Jonathan Gootenberg

1 year

@genomerambler “I am become death” I tell myself as I set up my MTT assay

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Jonathan Gootenberg

3 years

Of course, a single transcript isn’t often enough to characterize a cell state or type. What about some logic? We show both OR and AND logic. (We also find that 2-input logic is enough to distinguish 35/37 tissue types according to GTEx) 9/13

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Jonathan Gootenberg

10 months

We’d also like to note the fantastic work from @zhangf , Makoto Saito, Peiyu Xu , comprehensively mapping the structure and engineering of Fanzors. Excited to see where the field takes Fanzors! 6/6

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Fanzor is a eukaryotic programmable RNA-guided endonuclease

Nature - Fanzor is shown to be an RNA-guided DNA endonuclease, demonstrating that such endonucleases are found in all domains of life and indicating a potential new tool for genome engineering...

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Jonathan Gootenberg

1 year

What about the nucleus? To access the nuclear genome, HERMES elements harbor NLS, which we show are sufficient for nuclear localization. 11/14

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Jonathan Gootenberg

1 year

HERMES are abundant across the eukaryotic tree of life, and they’ve acquired introns as well, implying co-evolution with their host genomes. 9/14

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Jonathan Gootenberg

2 years

Amazing story (and biology, LMNB1 mutations are fascinating). Of course, a strong reminder of the need for gene/gene editing therapies @growingwisdom

@owasow

Omar Wasow | @[email protected]

2 years

“It seemed absolutely crazy. The idea that an Iowa housewife, equipped with the cutting-edge medical tool known as Google Images, would make a medical discovery about a pro athlete who sees doctors and athletic trainers as part of her job?”

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Jonathan Gootenberg

12 days

We view EVOLVEpro as a great example of “cyborg” methods, where synergistic iterations between the dry and wet lab can go farther than either alone. You can try it out now on any protein you want! 7/7

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GitHub - idmjky/EvolvePro: PLM based active learning model for protein engineering

PLM based active learning model for protein engineering - idmjky/EvolvePro

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Jonathan Gootenberg

3 years

As an aside -- this collateral activity enabled us to detect the presence of a target nucleic acid, forming the basis for #CRISPRDiagnostics . More on that here, if interested: 5/n

@omarabudayyeh

Omar Abudayyeh

3 years

In the latest issue of @ScienceMagazine , @jgooten and I share our perspective on how #CRISPR diagnostics have rapidly progressed from the lab to the clinic and the potential it has for transforming detection of disease. One day we will have #CRISPR in every home for personal dx

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Jonathan Gootenberg

1 year

We searched for eukaryotic relatives of TnpB, finding abundant examples (100x more than the previous Fanzors). These systems, which we name HERMES, have spread across eukaryotes and their viruses, including animals, fungi, and algae. 4/14

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Jonathan Gootenberg

1 year

RNA-guided nucleases are abundant in prokaryotes, including both CRISPR effectors and their ancestors. One CRISPR ancestor, TnpB, has eukaryotic homologs – the Fanzor proteins (first found in 2013!). Are these Fanzors nucleases? Could there be more proteins like them? 3/14

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Jonathan Gootenberg

3 years

Type III systems are known to target RNA, but they have a lot of different pieces...making them tough to use as a tool in mammalian cells. In type III-E systems, the Cas7-11 evolved by the consolidation of Cas7 and Cas11 domains...so Cas7-11 (Credit to Eugene for the name). 7/n

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Jonathan Gootenberg

4 years

@hsiung_chris Back in grad school we had a great version cooked up by @SKonermann -- it's in the screening Nature Protocols. Check out step 102!

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Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening

Nature Protocols - This protocol from Feng Zhang's lab enables genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system, as sgRNA libraries are constructed...

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Jonathan Gootenberg

1 year

HERMES nucleases raise a whole slew of questions – what is their role? Are they involved in transposon life cycles? How can we use them as a substrate for new biotechnologies? We hope these directions will serve as the starting point for many interesting stories! 13/14

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Jonathan Gootenberg

3 years

How does RADARS work? We were inspired by RNA editing tools, including our work on the REPAIR editing system, which use a guide RNA to direct RNA editing (A->I) on a transcript in the cell. Quite useful, especially for removal of stop codons in genetic disease (UAG -> UIG) 3/13

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Jonathan Gootenberg

8 months

With the efforts at @Tome_bio , we're looking forward to bringing these advances to patients. Incredibly proud of the team, especially CEO @rkmailbox , CSO John Finn and our amazing investors @JorgeCondeBio @rtnarch @drcwestphal , @aradovicm , Alan Crane, and Dan Lynch

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Jonathan Gootenberg

3 years

We showed that 7-11 could programmably target RNA in a test tube and in bacteria, and we were interested if it could target RNA in mammalian cells, without collateral. 10/n

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Jonathan Gootenberg

3 years

The unique evolutionary path of Cas7-11 and the type III-E systems blurs the lines in CRISPR taxonomy, and it’s a great example of how a neat thread of basic research can turn into a new platform for tools. Plasmids should be up on @addgene shortly! 12/n

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