Noah Holzleitner
@noahholzleitner.bsky.social
PhD Student at Grünewald Lab (TUM)
🧬Protein Design for CRISPR proteins🧑🏽💻👨🏽🎨
🧬Protein Design for CRISPR proteins🧑🏽💻👨🏽🎨
Reposted by Noah Holzleitner
Check out our newest work! This is a story on how to get selectivity in binders - both isoform and site selectivity. Read the paper or enjoy this brief Skytorial of what we did!
www.biorxiv.org/content/10.1...
1/n
www.biorxiv.org/content/10.1...
1/n
PANCS-spec-Binders: A system for rapidly discovering isoform- or epitope-specific binders
Proteins that bind to a target protein of interest, termed "binders," are essential components of biological research reagents and therapeutics. Target proteins present multiple binding surfaces with ...
www.biorxiv.org
November 19, 2025 at 6:10 PM
Check out our newest work! This is a story on how to get selectivity in binders - both isoform and site selectivity. Read the paper or enjoy this brief Skytorial of what we did!
www.biorxiv.org/content/10.1...
1/n
www.biorxiv.org/content/10.1...
1/n
Reposted by Noah Holzleitner
Our work developing a parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording is now out @natbiotech.nature.com
A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording - @jshendure.bsky.social @troymcdiarmid.bsky.social @uwgenome.bsky.social go.nature.com/49eTPCu
A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording - Nature Biotechnology
Prime editing in mammalian cells benefits from a comprehensive list of genetic parts.
go.nature.com
November 12, 2025 at 6:06 PM
Our work developing a parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording is now out @natbiotech.nature.com
Reposted by Noah Holzleitner
New preprint from
@gocastelobranco.bsky.social lab!! We use MPRA & scCRISPRi/a to interrogate possible functions of GWAS-identified Multiple sclerosis risk SNPs in iPSC-derived oligodendrocytes.
www.biorxiv.org/content/10.1...
@gocastelobranco.bsky.social lab!! We use MPRA & scCRISPRi/a to interrogate possible functions of GWAS-identified Multiple sclerosis risk SNPs in iPSC-derived oligodendrocytes.
www.biorxiv.org/content/10.1...
www.biorxiv.org
November 13, 2025 at 8:35 AM
New preprint from
@gocastelobranco.bsky.social lab!! We use MPRA & scCRISPRi/a to interrogate possible functions of GWAS-identified Multiple sclerosis risk SNPs in iPSC-derived oligodendrocytes.
www.biorxiv.org/content/10.1...
@gocastelobranco.bsky.social lab!! We use MPRA & scCRISPRi/a to interrogate possible functions of GWAS-identified Multiple sclerosis risk SNPs in iPSC-derived oligodendrocytes.
www.biorxiv.org/content/10.1...
Reposted by Noah Holzleitner
Fantastic Gioele!
🧠 The Lipid #Brain Atlas is out now! If you think #lipids are boring and membranes are all the same, prepare to be surprised. Led by @lucafusarbassini.bsky.social with Giovanni D'Angelo's lab, we mapped membrane lipids in the mouse brain at high resolution.
www.biorxiv.org/cgi/content/...
www.biorxiv.org/cgi/content/...
October 16, 2025 at 7:47 AM
Fantastic Gioele!
Super interesting! Love the “Turning an Art into Science” aspect 🧬
Our latest work seeks to answer a longstanding question: why is discovering new protein binders seemingly unpredictable – and can we better quantify and understand the de novo binder discover process? 1/12
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Mapping the diverse topologies of protein-protein interaction fitness landscapes
De novo binder discovery is unpredictable and inefficient due to a lack of quantitative understanding of protein-protein interaction (PPI) sequence-function landscapes. Here, we use our PANCS-Binder t...
www.biorxiv.org
October 15, 2025 at 6:52 PM
Super interesting! Love the “Turning an Art into Science” aspect 🧬
Reposted by Noah Holzleitner
Anyone from the Bio community already got their hands on a NVidia DGX Spark for structure prediction and Protein design workloads ?
October 15, 2025 at 5:43 AM
Anyone from the Bio community already got their hands on a NVidia DGX Spark for structure prediction and Protein design workloads ?
Reposted by Noah Holzleitner
Mapping the diverse topologies of protein-protein interaction fitness landscapes https://www.biorxiv.org/content/10.1101/2025.10.14.682342v1
October 15, 2025 at 3:03 AM
Mapping the diverse topologies of protein-protein interaction fitness landscapes https://www.biorxiv.org/content/10.1101/2025.10.14.682342v1
Reposted by Noah Holzleitner
Two group leader positions available in the broader areas of RNA science, RNA technologies, and RNA medicine. Attractive packages and a great environment. Come and join us at Helmholtz RNA Würzburg, Bavaria.
October 8, 2025 at 9:45 PM
Two group leader positions available in the broader areas of RNA science, RNA technologies, and RNA medicine. Attractive packages and a great environment. Come and join us at Helmholtz RNA Würzburg, Bavaria.
Reposted by Noah Holzleitner
In any case, I am happy that we were lucky enough to receive funding and am excited to be working on the project. To everyone else who have also been rejected multiple times, I wish you the best of luck—if you are lucky enough to be in a position where you can try again. 13/n; n=13
October 8, 2025 at 8:06 AM
In any case, I am happy that we were lucky enough to receive funding and am excited to be working on the project. To everyone else who have also been rejected multiple times, I wish you the best of luck—if you are lucky enough to be in a position where you can try again. 13/n; n=13
Reposted by Noah Holzleitner
Directed evolution of a compact TranC11a system for efficient genome editing [new]
Evolved compact TranC11a matched SpCas9 edit, trait mod in plant/human.
Evolved compact TranC11a matched SpCas9 edit, trait mod in plant/human.
September 29, 2025 at 3:17 AM
Directed evolution of a compact TranC11a system for efficient genome editing [new]
Evolved compact TranC11a matched SpCas9 edit, trait mod in plant/human.
Evolved compact TranC11a matched SpCas9 edit, trait mod in plant/human.
Reposted by Noah Holzleitner
The team is already working to expand the platform’s abilities, including testing in clinically relevant immune and stem cells, and engineering future versions of the system that can rearrange sequences beyond one megabase.
Learn more in the full paper: www.science.org/doi/10.1126/...
Learn more in the full paper: www.science.org/doi/10.1126/...
Megabase-scale human genome rearrangement with programmable bridge recombinases
Bridge recombinases are naturally occurring RNA-guided DNA recombinases that we previously demonstrated can programmably insert, excise, and invert DNA in vitro and in Escherichia coli. In this study,...
www.science.org
September 25, 2025 at 6:27 PM
The team is already working to expand the platform’s abilities, including testing in clinically relevant immune and stem cells, and engineering future versions of the system that can rearrange sequences beyond one megabase.
Learn more in the full paper: www.science.org/doi/10.1126/...
Learn more in the full paper: www.science.org/doi/10.1126/...
Looks very nice!
Or go behind-the-scenes with the co-authors in this conversation about the work: arcinstitute.org/news/buildin...
Building “Germinal” for AI-Designed Antibody Molecules | Arc Institute
Going from designing individual genes to complete genomes is an incredibly challenging problem. We have previously shown that the genomic foundation models like the Evo series can generate single prot...
arcinstitute.org
September 24, 2025 at 4:16 PM
Looks very nice!
Reposted by Noah Holzleitner
Reduction of prime editing errors by engineered Cas9 variants with relaxed nick positioning. #NBThighlight www.nature.com/articles/s41...
Engineered prime editors with minimal genomic errors - Nature
Engineered prime editor systems with reduced occurrences of unwanted insertions or deletions during genome editing are developed.
www.nature.com
September 22, 2025 at 11:54 AM
Reduction of prime editing errors by engineered Cas9 variants with relaxed nick positioning. #NBThighlight www.nature.com/articles/s41...
Reposted by Noah Holzleitner
very cool work and a milestone in synthetic biology. how impressive are the new phage genomes?
with generative bioML, i'm always looking at how similar the generated sequences are to known sequences. let's take a look
with generative bioML, i'm always looking at how similar the generated sequences are to known sequences. let's take a look
Many of the most complex and useful functions in biology emerge at the scale of whole genomes.
Today, we share our preprint “Generative design of novel bacteriophages with genome language models”, where we validate the first, functional AI-generated genomes 🧵
Today, we share our preprint “Generative design of novel bacteriophages with genome language models”, where we validate the first, functional AI-generated genomes 🧵
September 18, 2025 at 3:30 AM
very cool work and a milestone in synthetic biology. how impressive are the new phage genomes?
with generative bioML, i'm always looking at how similar the generated sequences are to known sequences. let's take a look
with generative bioML, i'm always looking at how similar the generated sequences are to known sequences. let's take a look
Reposted by Noah Holzleitner
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 Noah Holzleitner
Looking for a new approach to studying or eliminating phages? Check out our study introducing anti-phage ASOs (antisense oligos) out in @Nature today. nature.com/articles/s4158…
September 10, 2025 at 3:40 PM
Looking for a new approach to studying or eliminating phages? Check out our study introducing anti-phage ASOs (antisense oligos) out in @Nature today. nature.com/articles/s4158…
Reposted by Noah Holzleitner
Recently tested some de-novo minibinders against two targets (thanks Adaptyv!) designed using our open-source design library, `mosaic`; our best method got hit rates of 7/10 and 8/10 and affinities as low as single-digit nanomolar. Wrote up some thoughts here: blog.escalante.bio/minibinder-d...
September 2, 2025 at 2:39 PM
Recently tested some de-novo minibinders against two targets (thanks Adaptyv!) designed using our open-source design library, `mosaic`; our best method got hit rates of 7/10 and 8/10 and affinities as low as single-digit nanomolar. Wrote up some thoughts here: blog.escalante.bio/minibinder-d...
Reposted by Noah Holzleitner
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 Noah Holzleitner
RFdiffusion2 is now live!
github.com/RosettaCommo...
You can now design proteins, and in particular enzymes from just partially defined amino acid side chains, and without defining their sequence position or order!
github.com/RosettaCommo...
You can now design proteins, and in particular enzymes from just partially defined amino acid side chains, and without defining their sequence position or order!
August 22, 2025 at 12:51 AM
RFdiffusion2 is now live!
github.com/RosettaCommo...
You can now design proteins, and in particular enzymes from just partially defined amino acid side chains, and without defining their sequence position or order!
github.com/RosettaCommo...
You can now design proteins, and in particular enzymes from just partially defined amino acid side chains, and without defining their sequence position or order!
Reposted by Noah Holzleitner
If you use Boltz1/2, BioEmu, Chai1, or other MSA-dependent models, you’re likely using our ColabFold server. Please be considerate! Avoid large submissions across many IPs instead generate the MSA locally. Our server is an old-timer from 2014 and can’t handle that load.
August 15, 2025 at 5:48 PM
If you use Boltz1/2, BioEmu, Chai1, or other MSA-dependent models, you’re likely using our ColabFold server. Please be considerate! Avoid large submissions across many IPs instead generate the MSA locally. Our server is an old-timer from 2014 and can’t handle that load.
Reposted by Noah Holzleitner
(1/7)
Training biomolecular foundation models shouldn't be so hard. And open-source structure prediction is important. So today we're releasing two software packages: AtomWorks and RosettaFold3 (RF3)
[https://www.biorxiv.org/content/10.1101/2025.08.14.670328v2](www.biorxiv.org/content/10.1...)
Training biomolecular foundation models shouldn't be so hard. And open-source structure prediction is important. So today we're releasing two software packages: AtomWorks and RosettaFold3 (RF3)
[https://www.biorxiv.org/content/10.1101/2025.08.14.670328v2](www.biorxiv.org/content/10.1...)
Accelerating Biomolecular Modeling with AtomWorks and RF3
Deep learning methods trained on protein structure databases have revolutionized biomolecular structure prediction, but developing and training new models remains a considerable challenge. To facilita...
www.biorxiv.org
August 15, 2025 at 5:17 PM
(1/7)
Training biomolecular foundation models shouldn't be so hard. And open-source structure prediction is important. So today we're releasing two software packages: AtomWorks and RosettaFold3 (RF3)
[https://www.biorxiv.org/content/10.1101/2025.08.14.670328v2](www.biorxiv.org/content/10.1...)
Training biomolecular foundation models shouldn't be so hard. And open-source structure prediction is important. So today we're releasing two software packages: AtomWorks and RosettaFold3 (RF3)
[https://www.biorxiv.org/content/10.1101/2025.08.14.670328v2](www.biorxiv.org/content/10.1...)
Reposted by Noah Holzleitner
Exploring the deletion landscape of S. aureus Cas9 with SABER [new]
SABER maps SaCas9 deletion tolerance for DNA binding, informing design of minimized CRISPRi repressors, revealing insights into SaCas9 structure.
SABER maps SaCas9 deletion tolerance for DNA binding, informing design of minimized CRISPRi repressors, revealing insights into SaCas9 structure.
August 13, 2025 at 3:27 AM
Exploring the deletion landscape of S. aureus Cas9 with SABER [new]
SABER maps SaCas9 deletion tolerance for DNA binding, informing design of minimized CRISPRi repressors, revealing insights into SaCas9 structure.
SABER maps SaCas9 deletion tolerance for DNA binding, informing design of minimized CRISPRi repressors, revealing insights into SaCas9 structure.
Reposted by Noah Holzleitner
This preprint from Helen Sakharova is one of the coolest things to come out of my lab: “Protein language models reveal evolutionary constraints on synonymous codon choice.” Codon choice is a big puzzle in how information is encoded in genomes, and we have a new angle. www.biorxiv.org/content/10.1...
Protein language models reveal evolutionary constraints on synonymous codon choice
Evolution has shaped the genetic code, with subtle pressures leading to preferences for some synonymous codons over others. Codons are translated at different speeds by the ribosome, imposing constrai...
www.biorxiv.org
August 7, 2025 at 8:29 AM
This preprint from Helen Sakharova is one of the coolest things to come out of my lab: “Protein language models reveal evolutionary constraints on synonymous codon choice.” Codon choice is a big puzzle in how information is encoded in genomes, and we have a new angle. www.biorxiv.org/content/10.1...
Reposted by Noah Holzleitner
PANCS-Binders (phage-assisted noncontinuous selection of protein binders) screens multiple high-diversity protein libraries against a panel of dozens of targets for high-throughput binder discovery. @chembiobryan.bsky.social @mstyles-chembiol.bsky.social
www.nature.com/articles/s41...
www.nature.com/articles/s41...
August 6, 2025 at 7:49 PM
PANCS-Binders (phage-assisted noncontinuous selection of protein binders) screens multiple high-diversity protein libraries against a panel of dozens of targets for high-throughput binder discovery. @chembiobryan.bsky.social @mstyles-chembiol.bsky.social
www.nature.com/articles/s41...
www.nature.com/articles/s41...