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Connor Tou

@connorjtou.bsky.social
321 followers 124 following 20 posts

PhD from MIT BE, Kleinstiver lab || Editing genes and running mountains

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Reposted by Connor Tou
Molecular Cell @cp-molcell.bsky.social · 26/05/2026
INSTALLing recombinase-driven genome writing: Engineered single-stranded donors bypass innate immunity to enable large DNA integration
dlvr.it
INSTALLing recombinase-driven genome writing: Engineered single-stranded donors bypass innate immunity to enable large DNA integration
In a recent Nature article, Tou et al. introduce INSTALL, a strategy that couples immune-evasive circular single-stranded DNA (cssDNA) technology with recombinase-based genome editing to overcome innate immune barriers and enable the integration of large DNA cargos.
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Reposted by Connor Tou
Buchholz Lab @buchholzlab.bsky.social · 26/05/2026
Read the research highlight from Frank Buchholz in Molecular Cell on INSTALL - a recombinase-driven approach using engineered single-stranded donors that bypass innate immunity. www.sciencedirect.com/science/arti... #Science #Biotech #GeneTherapy #Innovation
sciencedirect.com
INSTALLing recombinase-driven genome writing: Engineered single-stranded donors bypass innate immunity to enable large DNA integration
In a recent Nature article, Tou et al.1 introduce INSTALL, a strategy that couples immune-evasive circular single-stranded DNA (cssDNA) technology wit…
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Reposted by Connor Tou
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 Connor Tou
Nature Reviews Genetics @natrevgenet.nature.com · 14/05/2026
New online! Immune-evasive DNA integration with INSTALL
dlvr.it
Immune-evasive DNA integration with INSTALL
Nature Reviews Genetics, Published online: 13 May 2026; doi:10.1038/s41576-026-00971-1In this Tools of the Trade article, Connor Tou presents INSTALL, a recombinase-driven, kilobase-scale DNA integration method that employs partially duplexed circular single-stranded DNA to evade the cellular immune system.
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Connor Tou @connorjtou.bsky.social · 13/05/2026
Lots of great advances on kilobase-sized DNA integration & non-viral DNA delivery from many groups at #ASGCT2026! More progress on INSTALL in the works as well. The future looks promising!
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Connor Tou @connorjtou.bsky.social · 13/05/2026
A small piece in @natrevgenet.nature.com on our INSTALL technology: Immune-evasive DNA + recombinases for non-viral gene insertion. www.nature.com/articles/s41...
nature.com
Immune-evasive DNA integration with INSTALL - Nature Reviews Genetics
In this Tools of the Trade article, Connor Tou presents INSTALL, a recombinase-driven, kilobase-scale DNA integration method that employs partially duplexed circular single-stranded DNA to evade the c...
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Reposted by Connor Tou
Nature Biotechnology @natbiotech.nature.com · 24/04/2026
Research Highlight: Immune-stealth DNA for large cargo integration www.nature.com/articles/s41...
nature.com
Immune-stealth DNA for large cargo integration - Nature Biotechnology
Nature Biotechnology - Immune-stealth DNA for large cargo integration
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Reposted by Connor Tou
Waggoner Lab @labwaggoner.bsky.social · 18/03/2026
Genome editing that avoids immune detection to integrate large DNA sequences @nature.com www.nature.com/articles/d41... on paper released last week by @bkleinstiver.bsky.social www.nature.com/articles/s41...
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Reposted by Connor Tou
Nature Biotechnology @natbiotech.nature.com · 13/03/2026
Immune-evasive cssDNA donors combined with recombinases facilitate kilobase-scale insertion of custom genetic cargos in human cells and mice. #NBThighlight 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 Connor Tou
Nature @nature.com · 12/03/2026
Nature research paper: Immune evasive DNA donors and recombinases license kilobase-scale writing go.nature.com/4b3e0E2
go.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 viral vectors.
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Connor Tou @connorjtou.bsky.social · 11/03/2026
This was a collaborative effort between Kleinstiver Lab (@bkleinstiver.bsky.social, @ferreiradasilvaj.bsky.social, David Rufino-Ramos), Musolino Lab (Patricia Musolino, Palani Kalailingam), Artzi Lab (Natalie Artzi, Eliz Amar-Lewis, Will Sawyer), & Full Circle Therapeutics (Howard We, Keqiang Xie).
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Connor Tou @connorjtou.bsky.social · 11/03/2026
While this study establishes initial POC, we’re excited about next-gen INSTALL systems and solutions to the recombinase side of the problem. Stay tuned! 👀 🚀 (13/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
Multiplexed immune marker assays and blood work further showed that INSTALL was largely immune-evasive at the physiological level. Minimization of CpG motifs, which are sensed by TLR9 in the endosome, further decreased markers to background levels in adult mice. (12/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
A hallmark sign of infection is recruitment of monocytes / macrophages to the site of inflammation. We stained for CD68+ cells in the liver and saw dramatic differences between dsDNA-treated and INSTALL-treated liver, confirming that INSTALL evaded DNA innate immunity at the cellular level. (11/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
Next, we stained liver tissue from our in vivo experiments for activated STING (= immune response): INSTALL looked very similar to PBS and mRNA-only controls, whereas dsDNA could make nearly every cell light up! This confirmed that INSTALL evaded DNA innate immunity at the molecular level. (10/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
Next, we conducted experiments to characterize immune response. First, we performed RNA-seq from primary human T-cells or THP-1 derived macrophages that were treated with recombinase mRNA and various donor types. dsDNA induced stark transcriptomic disruption whereas INSTALL minimized this. (9/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
INSTALL might enable non-viral DNA integration in vivo for the first time. We delivered INSTALL via LNPs into mice and saw striking differences in survival compared to dsDNA-treated mice, enabling us to detect in vivo integration. Further work to increase efficiencies is now underway. (8/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
We found that using a chemically modified “ePIP” (INSTALL-2e) outperformed dsDNA donors in immune-proficient contexts and more modestly in immune-deficient contexts. INSTALL functioned independently of cell cycle arrest, hinting that its more compact structure might aid nuclear localization. (7/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
By coupling recombinases and redesigned cssDNA in mammalian cells, we created INSTALL. We found that simple oligo annealing to reconstitute the recombinase binding site was sufficient for integration of a cssDNA donor. We call this oligo a “PIP” and the resulting molecule an “oDNA”. (6/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
Circular single-stranded DNA (cssDNA) offers immune-evasive promise, showing far better tolerance than dsDNA in primary T cells and in mice. However, canonical recombinases are incompatible with ssDNA. We looked to how cssDNA viruses and mobile elements have evolved around this. (5/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
Yet nearly all recombinase systems are bottlenecked by a key challenge: mammalian cells have evolved potent innate immune responses against double-stranded DNA (dsDNA) - the very form canonically required as a donor for integration. (4/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
Recombinases are powerful enzymes capable of integrating kilobase-sized DNA into a human genome. Recent technological advances are starting to expand their therapeutic potential by retargeting them to desired genomic loci. (3/13)
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Connor Tou @connorjtou.bsky.social · 11/03/2026
A persistent challenge in genome editing is allelic heterogeneity: dozens, hundreds, or thousands of different mutations can cause the same genetic disease. To scale genome editing, mutation-agnostic strategies that can insert a healthy gene at a specific genomic site are needed. (2/13)
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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 Connor Tou
Emma Chory, Ph.D. @chorye.bsky.social · 04/03/2026
Evolution navigated billions of challenges to get to us to where we are today. Directed evolution compresses this to a 1D axis. Imagine if you could sample 200 dimensions at once, with data to boot 📈 First @chorylab.bsky.social PACE preprint on our new system to tackle this: bit.ly/turboprance
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Reposted by Connor Tou
Endpoints News @endpts.com · 29/12/2025
🔎 Special report: Gene editing’s toolbox problem. Endpoints Senior Science Correspondent @scienceboss.bsky.social spoke with dozens of biotech leaders and scientists about the promise of new tools — and the growing frustration over how few cures have followed.
endpoints.news
Gene editing's search for a 'holy grail' has led to an explosion of tools, but few cures
Former Intellia scientist John Finn reflects on gene editing's evolution and the closure of Tome Biosciences, highlighting the industry's focus on tools over medicines.
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Reposted by Connor Tou
Innovative Genomics Institute @innovativegenomics.bsky.social · 20/10/2025
Congrats to IGI alum Connor Tou on being named a 2025 #STATWunderkind! At the IGI, Connor worked on CRISPR EvolvR in John Dueber's lab and now, as a Ph.D. student at MIT, he's working on genome engineering with large insertions.
STAT 2025 Wunderkinds Connor Tou he/him
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Reposted by Connor Tou
Sternberg Lab @sternberglab.bsky.social · 17/10/2025
1/10 Genome maintenance by telomerase is a fundamental process in nearly all eukaryotes. But where does it come from? Today, we report the discovery of telomerase homologs in a family of antiviral RTs, revealing an unexpected evolutionary origin in bacteria. www.biorxiv.org/content/10.1...
biorxiv.org
Antiviral reverse transcriptases reveal the evolutionary origin of telomerase
Defense-associated reverse transcriptases (DRTs) employ diverse and distinctive mechanisms of cDNA synthesis to protect bacteria against viral infection. However, much of DRT family diversity remains ...
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Reposted by Connor Tou
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 Connor Tou
STAT @statnews.com · 15/10/2025
Taking the stage are three of this year's #STATWunderkinds! Meet the class of 2025: www.statnews.com/wunderkinds/ #STATSummit
3 Wunderkinds sit on stage with a moderator
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Connor Tou @connorjtou.bsky.social · 15/10/2025
Thanks Dimitrios! 🙏
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Reposted by Connor Tou
Jason Ukman @jasonukman.bsky.social · 15/10/2025
At a time when conflict and cynicism seem to be shadowing much of health and medicine, @statnews.com is recognizing some of the brightest young minds in their fields this morning. www.statnews.com/wunderkinds/
statnews.com
Meet the 2025 STAT Wunderkinds
This year, as in past years, we've found inspiring stories and innovative research. All are blazing new trails as they attempt to answer some of the
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Connor Tou @connorjtou.bsky.social · 15/10/2025
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
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Kranzusch Lab @kranzuschlab.bsky.social · 05/09/2025
How can we understand the earliest events in evolution of eukaryotic immunity? @yao-li.bsky.social reports incredible molecular fossils of complete bacterial-like operons in eukaryotes that illuminate how animal immunity was first acquired from anti-phage defense www.biorxiv.org/content/10.1...
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Microsoft Research @msftresearch.bsky.social · 10/07/2025
Today in the journal Science: BioEmu from Microsoft Research AI for Science. This generative deep learning method emulates protein equilibrium ensembles – key for understanding protein function at scale. www.science.org/doi/10.1126/...
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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 Connor Tou
Nature Biotechnology @natbiotech.nature.com · 24/06/2025
Click editing uses DNA polymerases, HUH endonucleases and oligonucleotide templates for genome modification go.nature.com/3zPEIjp rdcu.be/erfhL
go.nature.com
Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases - Nature Biotechnology
Click editing uses DNA polymerases, HUH endonucleases and oligonucleotide templates for genome modification.
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Reposted by Connor Tou
Sternberg Lab @sternberglab.bsky.social · 11/06/2025
1/10 New pre-print(s) from the Sternberg Lab in collaboration with Leifu Chang's Lab! We uncover the unprecedented molecular mechanism of CRISPR-Cas12f-like proteins, which drive RNA-guided transcription independently of canonical promoter motifs. Full story here: www.biorxiv.org/content/10.1...
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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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Chris Fell @cfell.bsky.social · 09/04/2025
So excited to share our new paper out today in @nature.com. We repurposed R2 retrotransposons to create STITCHR, a tool that can make virtually any kind of edit in mammalian genomes including the scarless multi-kilobase scale insertions 🧵 www.nature.com/articles/s41...
nature.com
Reprogramming site-specific retrotransposon activity to new DNA sites - Nature
A study of retrotransposon activity repurposes a retroelement called R2Tocc to create a programmable system called STITCHR that enables diverse genome edits including efficient, scarless large pa...
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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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Connor Tou @connorjtou.bsky.social · 26/11/2024
Would also love to be added! 🙏
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Connor Tou @connorjtou.bsky.social · 17/11/2024
Thanks Dimitrios! Maybe almost time for a starter pack 🤔
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