A team led by University of Pittsburgh’s Graham Hatfull has developed a method to construct bacteriophages with entirely synthetic genetic material, allowing researchers to add and subtract genes at will. The findings open the field to new pathways for understanding how these bacteria-killing viruses work, and for potential therapy of bacterial infections.
As phages’ secrets are revealed, researchers will be able to engineer them with genomes tailor-made to attack specific bacteria, leading to new ways to combat the worsening problem of antibacterial resistance.
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“This will speed up discovery,” Hatfull said. There is massive variation among phages, but researchers don’t know the roles played by many individual genes. “How are the genes regulated? If a phage has 100 genes, does it need all 10? What happens if we remove this one or that one? We don’t have the answers to those questions,” he said, “but now we can ask–and answer–almost any question we have about phages.”
Reconstructing phages
For this research, the team reconstructed two naturally occurring phages that attack mycobacterium (which include the pathogens responsible for tuberculosis and leprosy, among others) using synthetic material. They then added and removed genes, successfully editing the synthetic genomes of both.
“And now, the sky’s the limit,” Hatfull said. “You can make any genome you want. You’re only limited by what you can imagine would be useful and interesting to make.”
Graham collaborated with Ansa Biotech and New England Biolabs, combining their unique techniques for synthesizing and assembling DNA with his expertise in phages and mycobacterium. The results of their work will be published in Proceedings of the National Academy of Sciences (PNAS).
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