Samuel King
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samuelhking.bsky.social
Samuel King
@samuelhking.bsky.social
Stanford Bioengineering PhD candidate / Biological AI in Brian Hie’s lab at Arc Institute

https://samuelking.cargo.site
Reposted by Samuel King
Tomorrow, at the #SystemsVirologyJournalClub, @samuelhking.bsky.social will present his work with @brianhie.bsky.social using AI genome language models to generate novel, high-fitness bacteriophages.
🚨 Systems Virology Journal Club – 8th Series! 🚨
#BillSchneider and I are delighted to announce another round of cutting-edge talks in #SystemsVirology! 🦠💡
Join us and an outstanding lineup of speakers, starting Oct 30.
Free registration: shiraweingartengabbay.com/systems-viro... 🔬✨
January 7, 2026 at 11:52 PM
Reposted by Samuel King
What if we could autocomplete DNA based on function?

Today in @Nature, we share semantic design—a strategy for function-guided design with genomic language models that leverages genomic context to create de novo genes and systems with desired functions. 🧵

www.nature.com/articles/s41...
November 19, 2025 at 4:31 PM
Reposted by Samuel King
In a new preprint from @brianhie.bsky.social's lab, the team reports the first generative design of viable bacteriophage genomes.

Leveraging Evo 1 & Evo 2, they generated whole genome sequences, resulting in 16 viable phages with distinct genomic architectures.
September 17, 2025 at 3:12 PM
Reposted by Samuel King
A landmark paper from Brian Hie’s group at the Arc Institute. The de novo design of the synthetic genome of an entirely novel biological entity

www.biorxiv.org/content/10.1...
Generative design of novel bacteriophages with genome language models
Many important biological functions arise not from single genes, but from complex interactions encoded by entire genomes. Genome language models have emerged as a promising strategy for designing biol...
www.biorxiv.org
September 17, 2025 at 5:37 PM
Reposted by Samuel King
Genome foundation models, Evo 1 and Evo 2, have now generated viable bacteriophage genomes, demonstrating experimental validation of whole genomes designed by AI!

@arcinstitute.org @brianhie.bsky.social @samuelhking.bsky.social

Read more at GEN:
www.genengnews.com/topics/artif...
AI Designs Viable Bacteriophage Genomes, Combats Antibiotic Resistance
AI-guided design of 16 functional bacteriophage genomes offers a path for phage-based therapies against antibiotic-resistant infections.
www.genengnews.com
September 17, 2025 at 3:21 PM
Also, check out our blog post giving a concise overview of the technical developments required for phage genome design arcinstitute.org/news/hie-kin.... Thanks to Arc Institute, Stanford Bioengineering, and all the other amazing people who supported this work 🧬
How We Built the First AI-Generated Genomes | 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 17, 2025 at 3:03 PM
We’re beyond excited for a new era of genome design and to see where researchers might take this. Read more in our preprint, and reach out if you have questions or thoughts! www.biorxiv.org/content/10.1...
Generative design of novel bacteriophages with genome language models
Many important biological functions arise not from single genes, but from complex interactions encoded by entire genomes. Genome language models have emerged as a promising strategy for designing biol...
www.biorxiv.org
September 17, 2025 at 3:03 PM
To explore the utility of our genome design method for creating resilient phage therapies, we evolved a generated phage cocktail against three different ΦX174-resistant E. coli strains. The generated cocktail rapidly overcame resistance against all strains while ΦX174 did not.
September 17, 2025 at 3:03 PM
By directly competing the phages against each other, we observed several generated phages that outcompeted ΦX174 or showed faster lytic dynamics, highlighting the ability of our method for designing high fitness mutations.
September 17, 2025 at 3:03 PM
The viable generated phages harbored hundreds of novel mutations, many of which do not map to any sequence seen in nature. The cryo-EM structure of one phage revealed a genome packaging mechanism designed by Evo that was previously found lethal in rational engineering attempts.
September 17, 2025 at 3:03 PM
We synthesized and tested 285 generated phage genomes in E. coli C. 16 generated phages inhibited growth in E. coli C but showed no off-target infection in E. coli strains outside of ΦX174’s natural range, demonstrating the intended host specificity.
September 17, 2025 at 3:03 PM
By fine-tuning Evo 1 and Evo 2 on Microviridae sequences, we honed the models’ understanding of ΦX174-like genomes, which allowed us to generate sequences fulfilling our design criteria with a high success rate.
September 17, 2025 at 3:03 PM
ΦX174 is a small Microviridae phage that infects its host E. coli C. It has a very intricate genetic architecture, making it a challenging template. We established our design criteria on ΦX174 and Microviridae sequences, including a “tropism constraint” for host specificity.
September 17, 2025 at 3:03 PM
We first needed clear design criteria to guide our genome generation process. As a design template, we chose ΦX174, a classic phage in molecular biology, which was the first genome ever sequenced and synthesized.
September 17, 2025 at 3:03 PM
But can DNA language models generate complete, viable genomes? To investigate this, we developed a modular framework for designing phages targeting a chosen bacteria, to maximize benefit for phage-based biotechnologies and therapeutics.
September 17, 2025 at 3:03 PM
DNA language models such as Evo 1 and Evo 2, trained on millions of genomes, learn complex features of genomes at an unfathomable scale. These models work much like ChatGPT, except for DNA. We’ve previously shown that they can generate novel CRISPR-Cas systems, amongst others.
We trained a genomic language model on all observed evolution, which we are calling Evo 2.

The model achieves an unprecedented breadth in capabilities, enabling prediction and design tasks from molecular to genome scale and across all three domains of life.
September 17, 2025 at 3:03 PM
Designing a genome is an incredibly complex task. The overwhelming number of considerations has limited what we’ve previously been able to achieve in synthetic biology.
September 17, 2025 at 3:03 PM
We chose to generate bacteriophage genomes, given their utility in biotechnology and therapeutics, and because they are safe and feasible to test in the lab. Phages are viruses that infect and kill bacteria, and are emerging as a promising strategy to combat rising antibiotic resistance.
September 17, 2025 at 3:03 PM
I’ll start by recognizing that this work wouldn’t have been possible without the incredible support of my PhD advisor @brianhie, and the brilliant labmates and scientists who I had the honor of working with:
September 17, 2025 at 3:03 PM
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 🧵
September 17, 2025 at 3:03 PM
Reposted by Samuel King
We trained a genomic language model on all observed evolution, which we are calling Evo 2.

The model achieves an unprecedented breadth in capabilities, enabling prediction and design tasks from molecular to genome scale and across all three domains of life.
February 19, 2025 at 4:42 PM
Reposted by Samuel King
Excited to have the first project of my PhD out!! By leveraging genomic language model Evo’s ability to learn relationships across genes (i.e., "know a gene by the company it keeps"), we show that we can use prompt-engineering to generate highly divergent proteins with retained functionality. 🧵1/N
December 19, 2024 at 6:54 PM