Phage engineering and the evolutionary arms race

Phages are versatile agents for delivering a variety of cargo, including nanomaterials, nucleic acids, and small molecules. A potentially important application is treatment of antibiotic-resistant infections. All of these applications require molecular engineering of the phages, including chemical modification and genetic engineering. Phages are remarkably amenable to such engineering. We review some examples, including for controlled phage therapy. We suggest that the ability of phages to support extensive engineering may have evolutionary origins in the billions-year-old ‘arms race’ between bacteria and phages, which selects for sequences and structures that are robust in the face of rapid evolutionary change. This leads to high tolerance of both naturally evolved mutations and synthetic molecular engineering.