Ben Kleinstiver
@bkleinstiver.bsky.social
Associate Professor @ Mass General Hospital & Harvard Medical School
Genome editing / Protein eng. / Molecular medicine 🇨🇦🧬
Kayden-Lambert MGH Research Scholar '23-28
Genome editing / Protein eng. / Molecular medicine 🇨🇦🧬
Kayden-Lambert MGH Research Scholar '23-28
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". ❤️👏
Crescendo: KJ's Dad on watching 🏈 with his son: "This is what we thought we would never get". ❤️👏
October 16, 2025 at 12:15 AM
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". ❤️👏
Crescendo: KJ's Dad on watching 🏈 with his son: "This is what we thought we would never get". ❤️👏
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
Really well deserved recognition for an innovator and emerging leader in our field! 👏 🙌
@mgbresearch.bsky.social @harvardmed.bsky.social
October 16, 2025 at 12:07 AM
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
Really well deserved recognition for an innovator and emerging leader in our field! 👏 🙌
@mgbresearch.bsky.social @harvardmed.bsky.social
Reposted by Ben Kleinstiver
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
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
https://bit.ly/gene_therapy_R179H
t.co
September 12, 2025 at 1:12 PM
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
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...
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 ...
www.nature.com
September 12, 2025 at 2:00 AM
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...
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...
Reposted by Ben Kleinstiver
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...
www.nature.com/articles/s41...
August 27, 2025 at 4:14 PM
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...
www.nature.com/articles/s41...
Reposted by Ben Kleinstiver
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)
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)
July 3, 2025 at 3:21 AM
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)
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)
Reposted by Ben Kleinstiver
🚨 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
Since the preprint, we added two super interesting findings. Short 🧵👇 (1/5)
www.cell.com/molecular-th...
#ImmunoSky #GeneEditing #CARTcells
May 23, 2025 at 7:39 PM
🚨 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
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..
Having a hard time processing this. HHMI is pausing all competitions. Very demoralizing for early career scientists like me @hhmi.org
May 16, 2025 at 4:52 PM
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..
Reposted by Ben Kleinstiver
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...
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...
May 15, 2025 at 10:49 PM
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...
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...
Reposted by Ben Kleinstiver
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
In new work @arcinstitute.org, we report the discovery and engineering of the first programmable DNA recombinases capable of megabase-scale human genome rearrangement
May 15, 2025 at 1:47 PM
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
In new work @arcinstitute.org, we report the discovery and engineering of the first programmable DNA recombinases capable of megabase-scale human genome rearrangement
Reposted by Ben Kleinstiver
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
www.nytimes.com
May 16, 2025 at 1:38 AM
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...
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 🙏
Congratulations to @rachelsilverstein9.bsky.social who designed the Cas9 enzyme that went into this drug.
Wishing K.J. & his family all the best 🙏
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.
A promising genetic treatment tailor-made for a baby born with a rare disorder
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.
www.npr.org
May 16, 2025 at 1:33 AM
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 🙏
Congratulations to @rachelsilverstein9.bsky.social who designed the Cas9 enzyme that went into this drug.
Wishing K.J. & his family all the best 🙏
Reposted by Ben Kleinstiver
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...
—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...
May 15, 2025 at 6:05 PM
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...
—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...
Reposted by Ben Kleinstiver
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
May 13, 2025 at 11:37 PM
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
Reposted by Ben Kleinstiver
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/
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/
May 12, 2025 at 8:00 PM
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/
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/
Reposted by Ben Kleinstiver
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
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
May 6, 2025 at 2:48 AM
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
rdcu.be/ekKtv
Reposted by Ben Kleinstiver
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
Custom CRISPR—Cas9 PAM variants via scalable engineering and machine learning - Nature
Nature - Custom CRISPR—Cas9 PAM variants via scalable engineering and machine learning
www.nature.com
April 23, 2025 at 10:57 AM
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
Reposted by Ben Kleinstiver
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...
www.nature.com/articles/s41...
Custom CRISPR—Cas9 PAM variants via scalable engineering and machine learning - Nature
Nature - Custom CRISPR—Cas9 PAM variants via scalable engineering and machine learning
www.nature.com
April 22, 2025 at 8:57 PM
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...
www.nature.com/articles/s41...
Reposted by Ben Kleinstiver
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
April 22, 2025 at 8:21 AM
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 👇
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 👇
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...
massgeneralbrigham.wd1.myworkdayjobs.com
March 13, 2025 at 4:39 PM
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 👇
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 👇
Reposted by Ben Kleinstiver
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.
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.
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
media.tenor.com
March 9, 2025 at 4:33 AM
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.
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.
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?...
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?...
Trump 2.0: Last Week Tonight with John Oliver (HBO)
YouTube video by LastWeekTonight
youtu.be
February 21, 2025 at 1:02 AM
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?...
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?...
Reposted by Ben Kleinstiver
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...
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...
www.biorxiv.org
December 9, 2024 at 1:05 PM
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...
Reposted by Ben Kleinstiver
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...
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...
www.biorxiv.org
November 26, 2024 at 5:32 AM
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...