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Ben Kleinstiver

@bkleinstiver.bsky.social
685 followers 152 following 62 posts

Associate Professor @ Mass General Hospital & Harvard Medical School Genome editing / Protein eng. / Molecular medicine 🇨🇦🧬 Kayden-Lambert MGH Research Scholar '23-28

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Reposted by Ben Kleinstiver
Connor Horton @connorhorton.bsky.social · 11/08/2026
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 🧵:
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Reposted by Ben Kleinstiver
Sternberg Lab @sternberglab.bsky.social · 03/08/2026
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...
cell.com
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...
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Reposted by Ben Kleinstiver
Doudna Lab @doudna-lab.bsky.social · 16/07/2026
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!
science.org
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 ...
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Ben Kleinstiver @bkleinstiver.bsky.social · 16/07/2026
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...
nature.com
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 ...
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Reposted by Ben Kleinstiver
CGM at MGB @cgm-mgh.bsky.social · 12/05/2026
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.
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Reposted by Ben Kleinstiver
Nicholas Southern @neuroscinikolai.bsky.social · 05/07/2026
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! 😄
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Connor Tou @connorjtou.bsky.social · 11/03/2026
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
nature.com
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 ...
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Reposted by Ben Kleinstiver
CGM at MGB @cgm-mgh.bsky.social · 16/03/2026
Congratulations to CGM and Pathology Faculty Dr. Benjamin Kleinstiver (@bkleinstiver.bsky.social), winner of the 2026 Martin Prize in Fundamental Research!
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Ben Kleinstiver @bkleinstiver.bsky.social · 10/03/2026
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/...
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Ben Kleinstiver @bkleinstiver.bsky.social · 16/10/2025
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". ❤️👏
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Ben Kleinstiver @bkleinstiver.bsky.social · 16/10/2025
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
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Reposted by Ben Kleinstiver
ACTA2 Alliance @acta2alliance.bsky.social · 12/09/2025
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
t.co
https://bit.ly/gene_therapy_R179H
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Ben Kleinstiver @bkleinstiver.bsky.social · 12/09/2025
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...
nature.com
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 ...
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Martin Pacesa @martinpacesa.bsky.social · 27/08/2025
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...
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Max Wilkinson @maxewilkinson.bsky.social · 03/07/2025
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)
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Reposted by Ben Kleinstiver
Dimitrios L. Wagner @dlwagner.bsky.social · 23/05/2025
🚨 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
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Ben Kleinstiver @bkleinstiver.bsky.social · 16/05/2025
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..
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Reposted by Ben Kleinstiver
Sternberg Lab @sternberglab.bsky.social · 15/05/2025
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...
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pdhsu.bsky.social @pdhsu.bsky.social · 15/05/2025
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
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Reposted by Ben Kleinstiver
Nature Biotechnology @natbiotech.nature.com · 16/05/2025
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...
nytimes.com
Baby Is Healed With World’s First Personalized Gene-Editing Treatment
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Ben Kleinstiver @bkleinstiver.bsky.social · 16/05/2025
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 🙏
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Eric Topol @erictopol.bsky.social · 15/05/2025
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...
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Michael Baym @baym.lol · 14/05/2025
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
A screenshot of the termination notice showing "Outstanding Investigator Grants"A screenshot of the termination notice with "This award is terminated effective the date of this award, due to unsafe antisemitic actions that suggest the institution lacks concern for the safety and wellbeing of Jewish students." highlighted
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Addgene @addgene.bsky.social · 12/05/2025
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/
Plasmid of the Day
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Reposted by Ben Kleinstiver
Nature Biotechnology @natbiotech.nature.com · 06/05/2025
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
go.nature.com
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.
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Reposted by Ben Kleinstiver
Nature Biotechnology @natbiotech.nature.com · 23/04/2025
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
nature.com
Custom CRISPR—Cas9 PAM variants via scalable engineering and machine learning - Nature
Nature - Custom CRISPR—Cas9 PAM variants via scalable engineering and machine learning
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Nature [Unofficial] @nature.com.web.brid.gy · 23/04/2025
nature.com
Custom CRISPR—Cas9 PAM variants via scalable engineering and machine learning
Nature, Published online: 22 April 2025; doi:10.1038/s41586-025-09021-y Custom CRISPR—Cas9 PAM variants via scalable engineering and machine learning
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Ben Kleinstiver @bkleinstiver.bsky.social · 22/04/2025
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...
nature.com
Custom CRISPR—Cas9 PAM variants via scalable engineering and machine learning - Nature
Nature - Custom CRISPR—Cas9 PAM variants via scalable engineering and machine learning
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Reposted by Ben Kleinstiver
Ross Wilson @rosswilsonlab.org · 22/04/2025
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
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Ben Kleinstiver @bkleinstiver.bsky.social · 13/03/2025
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 👇
massgeneralbrigham.wd1.myworkdayjobs.com
Research Technician I - Center for Genomic Medicine
Site: The General Hospital Corporation At Mass General Brigham, we know it takes a surprising range of talented professionals to advance our mission—from doctors, nurses, business people and tech expe...
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Jeremy Berg @jeremymberg.bsky.social · 09/03/2025
Bluetorial: Women, courage, and leadership What follows will include some generalizations based on population averages of what I have experienced over the course of my career. There are, of course, exceptions in every group who are substantially more to one extreme or the other.
media.tenor.com
a cartoon says hey everybody an old man 's talking while bart simpson looks on
ALT: a cartoon says hey everybody an old man 's talking while bart simpson looks on
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Ben Kleinstiver @bkleinstiver.bsky.social · 21/02/2025
If you're unsure whether advocacy or protest to save life-saving research matters, an important message here starting at 33:00. Together we can prevent devastating healthcare & economic impacts, and save science that doesn't see red or blue.. We need your support! ✊🧬🔬🧑‍🔬 youtu.be/cw0F8G4-dMw?...
youtu.be
Trump 2.0: Last Week Tonight with John Oliver (HBO)
YouTube video by LastWeekTonight
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Reposted by Ben Kleinstiver
Haley Lab @labohaley.bsky.social · 09/12/2024
Have you been interested combining Perturb-Seq screening with Cas12a’s unique capabilities for multiplexed guide RNA expression? Us too! So, we figured out some useful tricks to make that possible, which you can find in our new pre-print. Short thread below: www.biorxiv.org/content/10.1...
biorxiv.org
Degron-modified Cas12a enhances single-cell CRISPR screening
Single-cell CRISPR (Perturb-seq) screens have primarily relied on Cas9 whereas Cas12a, despite its unique effectiveness for multiplex guide expression, remains underexplored. This may be due to Cas12a...
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Rezwan Siddiquee @rezwansiddiquee.bsky.social · 26/11/2024
Very excited to share our new pre-print! We’ve developed a new way to put any type of cargo (biological or synthetic) into protein cages! All in-vitro! This enables massively scalable in vitro packaging technology for multiple lucrative applications. www.biorxiv.org/content/10.1...
biorxiv.org
High-fidelity in vitro packaging of diverse synthetic cargo into encapsulin protein cages
Cargo-filled protein cages are powerful tools in biotechnology with demonstrated potential as catalytic nanoreactors and vehicles for targeted drug delivery. While endogenous biomolecules can be packa...
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Julian Grünewald @grunewald.bsky.social · 26/11/2024
Very excited about the first preprint from our lab at TUM! This is a fun gene & cell therapy collaboration led by @schmidts.bsky.social's lab. We use generative #AI to design new #CARTcell therapies. Check out Andrea's thread & thanks to the whole team! www.biorxiv.org/content/10.1...
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Andrea Schmidts @schmidts.bsky.social · 26/11/2024
Cancer escapes immunotherapies by mutating its surface, meaning even groundbreaking #CARTCell therapies fail too often. But what if #GenerativeAI could design CAR-T with de novo binders faster, targeting resistant tumors? 🧵 www.biorxiv.org/content/10.1... (1)
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Ben Neely @benneely.com · 24/11/2024
I took biochem in 2001, and for nearly 20 years read amino acid sequences daily… and I never knew Dayhoff named them or even the logic behind things like Q until last Friday (h/t Mike Janech). Also, this is another big Dayhoff moment for me. She was incredible! #proteomics #bioinformatics
biology.arizona.edu
Dr. Margaret Oakley Dayhoff
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Anne O'Donnell-Luria @anneotation.bsky.social · 24/11/2024
We are pleased to share a preprint on the gene curation progress from the first 4 years of the ClinGen Syndromic Disorders Gene Curation Expert Panel (GCEP).
buff.ly
The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the Clinical Validity of 111 Gene-Disease Relationships
Purpose The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels (GCEPs) have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders GCEP…
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JT Neal @jtneal.bsky.social · 20/11/2024
new building, same problems
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John Doench @johndoench.bsky.social · 15/11/2024
Happy Friday! New preprint to discuss, led by @ekaplan.bsky.social, entitled "Activity-based selection for enhanced base editor mutational scanning" www.biorxiv.org/content/10.1... A thread...
biorxiv.org
Activity-based selection for enhanced base editor mutational scanning
Base editing is a CRISPR-based technology that enables high-throughput, nucleotide-level functional interrogation of the genome, which is essential for understanding the genetic basis of human disease...
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