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Updated: Aug 8, 2026

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Synthesis of Infectious Bacteriophages in an E. coli-based Cell-free Expression System
Published on: August 17, 2017
Generative design of bacteriophages with genome language models
Samuel H King1,2, Claudia L Driscoll2,3, David B Li1,2
1Department of Bioengineering, Stanford University, Stanford, CA, USA.
Summary
Researchers generated complete bacteriophage genomes using AI, creating viable phages with specific host targeting. This AI-driven approach offers a new path for developing phage therapies against drug-resistant bacteria.
Area of Science:
- Synthetic biology
- Genomics
- Artificial intelligence
Background:
- Biological functions often result from complex genomic interactions, not just single genes.
- Bacteriophages (phages) are viruses that infect bacteria and have therapeutic potential.
- Developing novel phages for specific applications requires advanced design tools.
Purpose of the Study:
- To report the first generative design of complete bacteriophage genomes using genome language models.
- To create viable phages with targeted host tropism.
- To demonstrate a pathway for AI-generated phage therapies.
Main Methods:
- Utilized genome language models for generative design of bacteriophage genomes.
- Employed the phage ΦX174 as a design template.
- Conducted experimental testing of generated phages and used cryo-electron microscopy for structural analysis.
Main Results:
- Successfully generated viable bacteriophages with targeted host tropism.
- Obtained 16 phages with diverse fitness profiles under laboratory conditions.
- Confirmed the use of an evolutionarily distant DNA packaging protein in a generated phage's capsid via cryo-electron microscopy.
- Demonstrated that a cocktail of generated phages can overcome phage-resistant *Escherichia coli* strains.
Conclusions:
- Generative design of complete bacteriophage genomes is feasible using genome language models.
- AI-generated phages show potential for overcoming antibiotic-resistant bacterial pathogens.
- This work provides a blueprint for designing diverse synthetic bacteriophages and genome-scale biological systems.
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