In May, an international team of researchers and clinicians reported they successfully treated a seriously ill teenager with cystic fibrosis who had disseminated infection by Mycobacterium abscessus using a cocktail of genetically engineered phage1 . According to the University of Pittsburgh’s Graham Hatfull, who led the research team, this accomplishment represents a number of firsts: the first genetically engineered phage treatment—in this case, to convert a lysogenic phage to a lytic variety—and the first treatment of a mycobacterium. It also bodes well for a therapy that has long been dismissed by Western practitioners, as well as for the future of synthetic-biology approaches to the vexing problem of antibiotic-resistant bacteria. This news follows last year’s launch of a phage translational research center at the University of California, San Diego (UCSD), another sign of optimism in this old but controversial approach for treating bacterial infections. Supported with a three-year, $1.2 million grant from the UCSD chancellor, the new Center for Innovative Phage Applications and Therapeutics (IPATH) is applying “the same principles of clinical evaluation and development to phage therapy that would be applied to any other therapeutic entity,” says center co-director Robert Schooley, a physician and infectious disease specialist at UCSD. A worsening crisis of multi-drugresistant (MDR) infections, along with advanced technologies for characterizing viruses and their host interactions, is prompting a re-evaluation of phage therapy. And pharma, which has steered clear of antibiotics, let alone phage-derived ones, may be taking notice. Johnson & Johnson struck two deals centered on phage in January: one with Locus Biosciences, worth upwards of $818 million, to develop CRISPR phages, and the other with the Israeli company BiomX, which is applying phage therapy to dysbiosis of the microbiome. Still, previous experience, mostly in the context of compassionate-use phage treatments, has shown the approach to be hit-and-miss, time-consuming and expensive. To turn bacteriophage from a laboratory tool into an efficacious therapeutic for broader markets, companies are seeking to scale up production and deliver potent phage products under good manufacturing practices (GMP) quickly and reliably. Can companies deliver on expectations? We may get the answer soon as several companies developing phage therapies—AmpliPhi Biosciences, Adaptive Phage Therapeutics and Intralytix— move toward the clinic this year.
Read more at https://www.nature.com/articles/s41587-019-0133-z
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