Arc Institute
@arcinstitute.org
A new scientific institution for curiosity-driven biomedical science and technology.
By enabling exploration of a combinatorial perturbation space that approaches the diversity accessed by natural evolution, CRISPR All opens new possibilities for both biological discovery and therapeutic design.
Learn more in the preprint: www.biorxiv.org/content/10.1...
Learn more in the preprint: www.biorxiv.org/content/10.1...
A unified genetic perturbation language for human cellular programming
Evolution simultaneously and combinatorially explores complex genetic changes across perturbation classes, including gene knockouts, knockdowns, overexpression, and the creation of new genes from exis...
www.biorxiv.org
November 20, 2025 at 6:35 PM
By enabling exploration of a combinatorial perturbation space that approaches the diversity accessed by natural evolution, CRISPR All opens new possibilities for both biological discovery and therapeutic design.
Learn more in the preprint: www.biorxiv.org/content/10.1...
Learn more in the preprint: www.biorxiv.org/content/10.1...
The strongest constructs from the pooled CACTUS proliferation screens were then validated independently, showing clear advantages in head-to-head competitive assays across all four major CRISPR All perturbation classes.
November 20, 2025 at 6:35 PM
The strongest constructs from the pooled CACTUS proliferation screens were then validated independently, showing clear advantages in head-to-head competitive assays across all four major CRISPR All perturbation classes.
Using this framework, the team built CACTUS, a curated library of 600+ proposed CAR and T-cell enhancements.
Evaluating them in matched conditions allowed the team to precisely identify which edits enhance function under chronic stimulation.
Evaluating them in matched conditions allowed the team to precisely identify which edits enhance function under chronic stimulation.
November 20, 2025 at 6:35 PM
Using this framework, the team built CACTUS, a curated library of 600+ proposed CAR and T-cell enhancements.
Evaluating them in matched conditions allowed the team to precisely identify which edits enhance function under chronic stimulation.
Evaluating them in matched conditions allowed the team to precisely identify which edits enhance function under chronic stimulation.
CRISPR All standardizes these approaches by giving every perturbation type a common DNA architecture. Genes, domains, knockouts and knockdowns are all interoperable and linked to a single mRNA-expressed barcode, enabling precise recovery of each cell’s engineered program.
November 20, 2025 at 6:35 PM
CRISPR All standardizes these approaches by giving every perturbation type a common DNA architecture. Genes, domains, knockouts and knockdowns are all interoperable and linked to a single mRNA-expressed barcode, enabling precise recovery of each cell’s engineered program.
Other editing methods remain siloed because knockouts, knockdowns, overexpression, and synthetic gene insertions each rely on distinct molecular systems.
November 20, 2025 at 6:35 PM
Other editing methods remain siloed because knockouts, knockdowns, overexpression, and synthetic gene insertions each rely on distinct molecular systems.
Leveraging semantic design across varied genomic systems, these findings suggest that Evo can reliably generate sequence diverse yet functional genes directly from context, opening the door to new possibilities in large-scale sequence exploration.
Read more: www.nature.com/articles/s41...
Read more: www.nature.com/articles/s41...
Semantic design of functional de novo genes from a genomic language model - Nature
By learning a semantics of gene function based on genomic context, the genomic language model Evo autocompletes DNA prompts to generate novel genes encoding protein and RNA molecules with defined acti...
www.nature.com
November 19, 2025 at 6:17 PM
Leveraging semantic design across varied genomic systems, these findings suggest that Evo can reliably generate sequence diverse yet functional genes directly from context, opening the door to new possibilities in large-scale sequence exploration.
Read more: www.nature.com/articles/s41...
Read more: www.nature.com/articles/s41...
Finally, the team scaled semantic design across prokaryotic genomes, using Evo to generate SynGenome––a collection of 120+ billion base pairs of AI-generated DNA that mirrors native genomic structure while producing sequences beyond those found in nature.
November 19, 2025 at 6:17 PM
Finally, the team scaled semantic design across prokaryotic genomes, using Evo to generate SynGenome––a collection of 120+ billion base pairs of AI-generated DNA that mirrors native genomic structure while producing sequences beyond those found in nature.
They next evaluated whether the approach extended to anti-CRISPR systems.
Evo was able to produce novel proteins that inhibited SpCas9 and improved phage survival, demonstrating its ability to propose functional products in systems where sequence-based approaches often fail.
Evo was able to produce novel proteins that inhibited SpCas9 and improved phage survival, demonstrating its ability to propose functional products in systems where sequence-based approaches often fail.
November 19, 2025 at 6:17 PM
They next evaluated whether the approach extended to anti-CRISPR systems.
Evo was able to produce novel proteins that inhibited SpCas9 and improved phage survival, demonstrating its ability to propose functional products in systems where sequence-based approaches often fail.
Evo was able to produce novel proteins that inhibited SpCas9 and improved phage survival, demonstrating its ability to propose functional products in systems where sequence-based approaches often fail.
To validate the approach, the team then applied semantic design to toxin–antitoxin systems.
Prompted on the genomic contexts typical of these pairs, Evo successfully generated a range of diverse candidates, including several experimentally confirmed toxins and antitoxins.
Prompted on the genomic contexts typical of these pairs, Evo successfully generated a range of diverse candidates, including several experimentally confirmed toxins and antitoxins.
November 19, 2025 at 6:17 PM
To validate the approach, the team then applied semantic design to toxin–antitoxin systems.
Prompted on the genomic contexts typical of these pairs, Evo successfully generated a range of diverse candidates, including several experimentally confirmed toxins and antitoxins.
Prompted on the genomic contexts typical of these pairs, Evo successfully generated a range of diverse candidates, including several experimentally confirmed toxins and antitoxins.
They began by testing if Evo had learned genomic semantics—the idea that genes with related functions appear in similar sequence contexts.
In sequence-recovery tests, Evo reliably reconstructed conserved genes from partial inputs, with accuracy improving across model versions.
In sequence-recovery tests, Evo reliably reconstructed conserved genes from partial inputs, with accuracy improving across model versions.
November 19, 2025 at 6:17 PM
They began by testing if Evo had learned genomic semantics—the idea that genes with related functions appear in similar sequence contexts.
In sequence-recovery tests, Evo reliably reconstructed conserved genes from partial inputs, with accuracy improving across model versions.
In sequence-recovery tests, Evo reliably reconstructed conserved genes from partial inputs, with accuracy improving across model versions.
In his award-winning essay, Uche describes how a failed model became a breakthrough that would reshape his research and open doors for new approaches to understanding and treating neurodegeneration.
Read today in @science.org: www.science.org/doi/10.1126/...
Read today in @science.org: www.science.org/doi/10.1126/...
The missing piece: Solving the 50-year puzzle of BMP synthesis in neurodegeneration
Solving the 50-year puzzle of BMP synthesis in neurodegeneration
www.science.org
November 13, 2025 at 8:19 PM
In his award-winning essay, Uche describes how a failed model became a breakthrough that would reshape his research and open doors for new approaches to understanding and treating neurodegeneration.
Read today in @science.org: www.science.org/doi/10.1126/...
Read today in @science.org: www.science.org/doi/10.1126/...
Hear from lead author, Alison Fanton as she walks through how the team achieved these results and what they could mean for the future of gene editing.
Blog: arcinstitute.org/news/large-s...
Video: youtube.com/watch?time_continue=1&v=DHg_TkN15XY
Blog: arcinstitute.org/news/large-s...
Video: youtube.com/watch?time_continue=1&v=DHg_TkN15XY
Site-specific DNA insertion into the human genome with engineered recombinases
YouTube video by Arc Institute
youtube.com
November 6, 2025 at 5:46 PM
Hear from lead author, Alison Fanton as she walks through how the team achieved these results and what they could mean for the future of gene editing.
Blog: arcinstitute.org/news/large-s...
Video: youtube.com/watch?time_continue=1&v=DHg_TkN15XY
Blog: arcinstitute.org/news/large-s...
Video: youtube.com/watch?time_continue=1&v=DHg_TkN15XY
The optimized enzymes work across difficult cell types, with 33% efficiency in non-dividing cells, 24% in embryonic stem cells & 17% in human T cells, providing a new blueprint for engineering precise genome-editing tools.
Learn more in the paper: www.nature.com/articles/s41...
Learn more in the paper: www.nature.com/articles/s41...
Site-specific DNA insertion into the human genome with engineered recombinases - Nature Biotechnology
Engineered DNA recombinases efficiently and specifically insert genetic cargos without the use of landing pads.
www.nature.com
November 6, 2025 at 5:46 PM
The optimized enzymes work across difficult cell types, with 33% efficiency in non-dividing cells, 24% in embryonic stem cells & 17% in human T cells, providing a new blueprint for engineering precise genome-editing tools.
Learn more in the paper: www.nature.com/articles/s41...
Learn more in the paper: www.nature.com/articles/s41...
The best variants achieved 97% specificity & up to 53% efficiency, a 7.5-fold increase in accuracy & 12-fold increase in efficiency over the starting enzyme.
This means researchers can now choose variants optimized for maximum efficiency, specificity, or a balance of both.
This means researchers can now choose variants optimized for maximum efficiency, specificity, or a balance of both.
November 6, 2025 at 5:46 PM
The best variants achieved 97% specificity & up to 53% efficiency, a 7.5-fold increase in accuracy & 12-fold increase in efficiency over the starting enzyme.
This means researchers can now choose variants optimized for maximum efficiency, specificity, or a balance of both.
This means researchers can now choose variants optimized for maximum efficiency, specificity, or a balance of both.
They tested thousands of mutations to identify which improved the enzyme, then used computational models to predict how combining mutations would impact performance, allowing them to build highly optimized variants rapidly.
November 6, 2025 at 5:46 PM
They tested thousands of mutations to identify which improved the enzyme, then used computational models to predict how combining mutations would impact performance, allowing them to build highly optimized variants rapidly.
The team developed a comprehensive engineering strategy to improve both efficiency & specificity, combining evolutionary screening to find better mutations, machine learning to predict which mutations work together & fusing the enzyme to dCas9 to guide it to the correct location.
November 6, 2025 at 5:46 PM
The team developed a comprehensive engineering strategy to improve both efficiency & specificity, combining evolutionary screening to find better mutations, machine learning to predict which mutations work together & fusing the enzyme to dCas9 to guide it to the correct location.
Recombinases are enzymes capable of inserting DNA at specific sites in the genome without needing to create double-strand breaks like CRISPR does.
Existing recombinases, however, have limitations–managing only ~5% efficiency & often hitting hundreds of off-target sites.
Existing recombinases, however, have limitations–managing only ~5% efficiency & often hitting hundreds of off-target sites.
November 6, 2025 at 5:46 PM
Recombinases are enzymes capable of inserting DNA at specific sites in the genome without needing to create double-strand breaks like CRISPR does.
Existing recombinases, however, have limitations–managing only ~5% efficiency & often hitting hundreds of off-target sites.
Existing recombinases, however, have limitations–managing only ~5% efficiency & often hitting hundreds of off-target sites.
By showing PTGES3 is an essential AR regulator, this work points to a new therapeutic strategy for overcoming treatment resistance in metastatic prostate cancer.
Learn more in the full paper: www.nature.com/articles/s41...
Learn more in the full paper: www.nature.com/articles/s41...
Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer - Nature Genetics
Genome-wide CRISPRi screens for modulators of androgen receptor (AR) protein levels using live-cell quantitative endogenous AR fluorescence reporters identify PTGES3 as a new regulator of AR stability...
www.nature.com
November 5, 2025 at 4:21 PM
By showing PTGES3 is an essential AR regulator, this work points to a new therapeutic strategy for overcoming treatment resistance in metastatic prostate cancer.
Learn more in the full paper: www.nature.com/articles/s41...
Learn more in the full paper: www.nature.com/articles/s41...
Importantly, PTGES3 is selectively required in AR-driven prostate cancer cells but not AR-independent cancer cells.
Unlike targeting HSP90, inhibiting PTGES3 offers a potentially more specific way to block AR without broadly disrupting the heat shock response.
Unlike targeting HSP90, inhibiting PTGES3 offers a potentially more specific way to block AR without broadly disrupting the heat shock response.
November 5, 2025 at 4:21 PM
Importantly, PTGES3 is selectively required in AR-driven prostate cancer cells but not AR-independent cancer cells.
Unlike targeting HSP90, inhibiting PTGES3 offers a potentially more specific way to block AR without broadly disrupting the heat shock response.
Unlike targeting HSP90, inhibiting PTGES3 offers a potentially more specific way to block AR without broadly disrupting the heat shock response.
In clinical findings, high PTGES3 expression predicts worse outcomes in patients treated with drugs like abiraterone & enzalutamide.
But loss of PTGES3 blocked tumor growth across multiple models of aggressive, therapy-resistant prostate cancer.
But loss of PTGES3 blocked tumor growth across multiple models of aggressive, therapy-resistant prostate cancer.
November 5, 2025 at 4:21 PM
In clinical findings, high PTGES3 expression predicts worse outcomes in patients treated with drugs like abiraterone & enzalutamide.
But loss of PTGES3 blocked tumor growth across multiple models of aggressive, therapy-resistant prostate cancer.
But loss of PTGES3 blocked tumor growth across multiple models of aggressive, therapy-resistant prostate cancer.
Through biochemical experiments & structural modeling, researchers showed that PTGES3 binds directly to AR in the nucleus. This binding interaction stabilizes AR protein & is required for AR to activate its target genes.
November 5, 2025 at 4:21 PM
Through biochemical experiments & structural modeling, researchers showed that PTGES3 binds directly to AR in the nucleus. This binding interaction stabilizes AR protein & is required for AR to activate its target genes.