I'm excited to share our work providing the first complete mechanistic picture of how R2 proteins nick the second strand, out today in @pnas.org! ✂️🧬 This step in retrotransposition has long been mysterious, but crucial for understanding R2's. Check it out: www.pnas.org/doi/10.1073/... A thread 🧵:

Out now! In collaboration with Hiroshi Nishimasu's lab, we uncover how a dual reverse transcriptase immune system builds double-stranded DNA from both RNA and protein templates. www.cell.com/cell/abstrac... Previous thread for the preprint: bsky.app/profile/ster...

Coordinated RNA- and protein-templated synthesis of double-stranded DNA by a dual reverse transcriptase immune system

Bacterial reverse transcriptases defend against viruses, yet how their DNA products stop infection remains unknown. Bacteriophage inhibition of a host recombination enzyme activates the DRT3 defense s...

cell.com

Our AI-guided design of RNA-guided nucleases is now out in @science.org 💻🧬 We used structure and evolutionary data to generate minimal, active and divergent gene editors! www.science.org/doi/10.1126/... Congrats to @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social & team!

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 multidomain proteins with robust enzymatic ...

science.org

A belated re-post after a brief sci-media hiatus - congratulations to @connorjtou.bsky.social & the team! We sought to overcome a key challenge for inserting large DNAs into the genome: toxicity & innate immune responses. 🧬 🚫 Our paper was published in @nature.com: www.nature.com/articles/s41...

Immune evasive DNA donors and recombinases license kilobase-scale writing - Nature

INSTALL overcomes fundamental challenges for DNA delivery and integration methods by synergizing immune-stealth nucleic acids with recombinases to enable kilobase-scale integration strategies without ...

nature.com

Connor Tou@connorjtou.bsky.social · 7mo ago

Today in @nature.com we introduce INSTALL, which bypasses mammalian DNA immune sensing to enable non-viral DNA integration with recombinases—a step toward safe, and mutation-agnostic genome editing. 🧬 🧵 (1/13) www.nature.com/articles/s41... @harvardmed.bsky.social @mgbresearch.bsky.social

Congratulations to Emily King, PhD (mentored by @bkleinstiver.bsky.social) who successfully defended her PhD thesis last week! The broader goal of her work is to shorten the path between technology development and therapeutic translation.

This project was driven by @m--mueller.bsky.social, a sharp and hardworking student who I had the pleasure of supervising the past 1.5 years (Here he is rocking one of our new POGO-PANCE t-shirts). He's now moved on to @bkleinstiver.bsky.social's group for an internship — definitely one to watch! 😄

Today in @nature.com we introduce INSTALL, which bypasses mammalian DNA immune sensing to enable non-viral DNA integration with recombinases—a step toward safe, and mutation-agnostic genome editing. 🧬 🧵 (1/13) www.nature.com/articles/s41... @harvardmed.bsky.social @mgbresearch.bsky.social

Immune evasive DNA donors and recombinases license kilobase-scale writing - Nature

INSTALL overcomes fundamental challenges for DNA delivery and integration methods by synergizing immune-stealth nucleic acids with recombinases to enable kilobase-scale integration strategies without ...

nature.com

Congratulations to CGM and Pathology Faculty Dr. Benjamin Kleinstiver (@bkleinstiver.bsky.social), winner of the 2026 Martin Prize in Fundamental Research!

Interested in gaining research experience, and curious about genome editing tool development and their application to treat human diseases? 🧬 🧫 We are hiring!! Join us at Mass General Hospital in Boston! 📣 massgeneralbrigham.wd1.myworkdayjobs.com/MGBExternal/...

An inspirational panel this morning with none other than baby KJ himself - highlighting the stories of heroes @ahrensnicklas.bsky.social & @kiranmusunuru.bsky.social ( hosted by @jasonmast.bsky.social). Crescendo: KJ's Dad on watching 🏈 with his son: "This is what we thought we would never get". ❤️👏

STAT@statnews.com · 12mo ago

Baby KJ, in a tiny tuxedo, shows up at the #STATSummit. His parents Kyle and Nicole Muldoon give an update on how he’s doing after his life-saving CRISPR treatment for a rare liver disease earlier this year. Read their story: www.statnews.com/2025/05/15/c...

Congrats to @connorjtou.bsky.social on being named a 2025 #STATWunderkind. His enthusiasm in the lab is contagious and he thrives on doing really hard things. Really well deserved recognition for an innovator and emerging leader in our field! 👏 🙌 @mgbresearch.bsky.social @harvardmed.bsky.social

Connor Tou@connorjtou.bsky.social · 12mo ago

Honored to be part of the 2025 #STATWunderkinds! Grateful for the many supportive mentors, colleagues, and friends with special shoutout to @bkleinstiver.bsky.social. Full list: www.statnews.com/wunderkinds/ @statnews.com @mitdeptofbe.bsky.social @mgbresearch.bsky.social @harvardmed.bsky.social

Back in June, at our MSMDS conference, we shared how researchers were advancing their work on gene editing for ACTA2 R179H. Today, we can celebrate that this effort is now peer-reviewed & published in @nature.com! 🎉 t.co/6WjTMRnAOi #MSMDS #ACTA2 @markelindsay.bsky.social @bkleinstiver.bsky.social

Optimization of a bespoke base editor to treat a severe pediatric vascular disease! 🫀🧬 Our manuscript describes: 1️⃣ Engineering a target-specific BE🧬 2⃣ A *must avoid* bystander edit that occurs with WT SpCas9 BEs! 🙅‍♂️ 3⃣ Extension of lifespan after in vivo editing! 🐁✅ www.nature.com/articles/s41...

Treatment of a severe vascular disease using a bespoke CRISPR–Cas9 base editor in mice - Nature Biomedical Engineering

Engineering a mutant-specific customized base editor precisely corrects a mutation while minimizing bystander edits, leading to substantial phenotypic recovery in mouse models of multisystemic smooth ...

nature.com

Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators. www.nature.com/articles/s41...

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)

🚨 Our work on optimizing single-stranded DNA donors with Cas12a binding moieties is published at @moltherapy.bsky.social Nucleic Acids! 🧪 Since the preprint, we added two super interesting findings. Short 🧵👇 (1/5) www.cell.com/molecular-th... #ImmunoSky #GeneEditing #CARTcells

Less than one day to celebrate a major win for science, before returning to our regularly scheduled programming of destruction of the American scientific enterprise and capitulation..

Chiara Masnovo@chiaramasnovophd.bsky.social · last yr.

Having a hard time processing this. HHMI is pausing all competitions. Very demoralizing for early career scientists like me @hhmi.org

1/10 Today in @science.org in collaboration with the Liu group we report the development of a laboratory-evolved CRISPR-associated transposase (evoCAST) that supports therapeutically relevant levels of RNA-programmable gene insertion in human cells. drive.google.com/file/d/1I-Ub...

Genomes encode biological complexity, which is determined by combinations of DNA mutations across millions of bases In new work @arcinstitute.org, we report the discovery and engineering of the first programmable DNA recombinases capable of megabase-scale human genome rearrangement

A gene-editing treatment used on a 9½-month-old boy with a rare condition has the potential to help people with thousands of other uncommon genetic diseases #NBTNewsBeat www.nytimes.com/2025/05/15/h...

Baby Is Healed With World’s First Personalized Gene-Editing Treatment

nytimes.com

An incredible collaborative effort led by @kiranmusunuru.bsky.social @ahrensnicklas.bsky.social @urnov.bsky.social & others. Congratulations to @rachelsilverstein9.bsky.social who designed the Cas9 enzyme that went into this drug. Wishing K.J. & his family all the best 🙏

NPR@npr.org · last yr.

For the first time, doctors have created a customized treatment using the revolutionary gene-editing technique known as CRISPR to treat a baby with a rare, life-threatening genetic disorder.

Today "a milestone in the evolution of personalized therapies for rare & ultra-rare inborn errors of metabolism" —the 1st human to undergo custom genome editing —from decades of NIH funded research www.nejm.org/doi/full/10.... @nejm.org www.nejm.org/doi/full/10.... www.nytimes.com/2025/05/15/h...

Yesterday, the NIH R35 “Outstanding Investigator” grant to fund scientists in my lab studying antibiotic resistance was terminated for reasons not related to the content of the science, or any actions taken by me or members of my lab

pCMV-T7-SpCas9(MKRCMV)-P2A-EGFP (AHK162) Depositor: Benjamin Kleinstiver @bkleinstiver.bsky.social Purpose: pCMV and pT7 Human expression plasmid for SpCas9 enzyme with MKRCMV amino acid substitutions www.addgene.org/223075/

The genome-wide landscape of Cas-induced double-strand breaks and end structures is profiled at nucleotide resolution go.nature.com/44DO2Cc rdcu.be/ekKtv

Linking CRISPR–Cas9 double-strand break profiles to gene editing precision with BreakTag - Nature Biotechnology

The genome-wide landscape of Cas-induced double-strand breaks and end structures is profiled at nucleotide resolution.

go.nature.com

By combining high-throughput protein engineering with machine learning, bespoke SpCas9 enzymes are identified that outperform evolution-based and engineered nucleases and base editors in human cells. www.nature.com/articles/s41... #NBTHighlight

In @nature.com we describe the use of scalable #proteinengineering & #machinelearning to predict millions of bespoke CRISPR enzymes, offering safer & more efficient genome editing tools 🧬🖥️ @rachelsilverstein9.bsky.social @mgbresearch.bsky.social @harvardmed.bsky.social www.nature.com/articles/s41...

Cas9 gets an upgrade! Check out our new paper in The CRISPR Journal: bit.ly/hiNLS-Cas9 Eric Noel (who is on the job market!) created Cas9 constructs w/ nuclear localization signals (NLS) in the backbone, boosting genome editing activity in T cells, as seen by editor @srishtisahu.bsky.social #CRISPR

Interested in learning more about genome editing tool dev & their application to treat human diseases? 🧬 🏥 We're hiring graduating seniors who are seeking ~2 years of post-bac research experience. If you're interested in gaining experience in next gen medicines, please reach out and apply! Link 👇