New method enables construction of complete mycobacteriophage genomes

A team co-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 therapies to fight the worsening problem of antibacterial resistance.   

“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? 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.” 

Hatfull 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 were published online this week in Proceedings of the National Academy of Sciences (PNAS).

The team constructed synthetic DNA modeled after two naturally occurring phages that attack mycobacterium (which include the pathogens responsible for tuberculosis and leprosy, among others). They then added and removed genes, successfully editing the synthetic genomes of both.  

Their work is published in Proceedings of the National Academy of Sciences (PNAS).

And now, the sky's the limit. You can make any genome you want. You're only limited by what you can imagine would be useful and interesting to make.”

Graham Hatfull, University of Pittsburgh