Viruses join fight against harmful bacteria To help achieve that goal, MIT biological engineers have devised a new mix-and-match system to genetically engineer viruses that target specific bacteria. This approach could generate new weapons against bacteria for which there are no effective antibiotics, says Timothy Lu, an associate professor of electrical engineering and computer science and biological engineering.ArrayArray"We'd like to be able to remove specific members of the bacterial population and see what their function is in the microbiome," Lu says. "In the longer term you could design a specific phage that kills that bug but doesn't kill the other ones, but more information about the microbiome is needed to effectively design such therapies."The paper's lead author is Hiroki Ando, an MIT research scientist. Other authors are MIT research scientist Sebastien Lemire and Diana Pires, a research fellow at the University of Minho in Portugal.ArrayThe Food and Drug Administration has approved a handful of bacteriophages for treating food products, but efforts to harness them for medical use have been hampered because isolating useful phages from soil or sewage can be a tedious, time-consuming process. Also, each family of bacteriophages can have a different genome organization and life cycle, making it difficult to engineer them and posing challenges for regulatory approval and clinical use.The MIT team set out to create a standardized genetic scaffold for their phages, which they could then customize by replacing the one to three genes that control the phages' bacterial targets.Array"You keep the majority of the phage the same and all you're changing is the tail region, which dictates what its target is," Lu says.To find genes to swap in, the researchers combed through databases of phage genomes looking for sequences that appear to code for the key tail fiber section, known as gp17.After the researchers identified the genes they wanted to insert into their phage scaffold, they had to create a new system for performing the genetic engineering. Existing techniques for editing viral genomes are fairly laborious, so the researchers came up with an efficient approach in which they insert the phage genome into a yeast cell, where it exists as an "artificial chromosome" separate from the yeast cell's own genome. During this process the researchers can easily swap genes in and out of the phage genome."Once we had that method, it allowed us very easily to identify the genes that code for the tails and engineer them or swap them in and out from other phages," Lu says. "You can use the same engineering strategy over and over, so that simplifies that workflow in the lab."ArrayArrayOne advantage of the engineered phages is that unlike many antibiotics, they are very specific in their targets. "Antibiotics can kill off a lot of the good flora in your gut," Lu says. "We aim to create effective and narrow-spectrum methods for targeting pathogens."Lu and his colleagues are now designing phages that can target other strains of harmful bacteria, which could have applications such as spraying on crops or disinfecting food, as well as treating human disease. Another advantage of this approach is that all of the phages are based on an identical genetic scaffold, which could streamline the process of getting regulatory approval, Lu says.