Nanoparticles show great promise for a variety of therapeutic and diagnostic (theranostic) applications. In particular, bacteriophages—viruses that infect bacteria—provide an attractive platform for the engineering of semisynthetic theranostic nanoparticles: They are biocompatible, noninfectious in humans, and essentially nontoxic to eukaryotic cells.

Importantly, “phage” particles can be modified both genetically and chemically to alter their surface characteristics in a defined manner. These advantages derive from a detailed understanding of virus biology, gleaned from decades of fundamental genetic, biochemical, and structural studies that have provided mechanistic insight into virus assembly pathways. Given the wealth of biochemical information available, it is not surprising that phages have been adapted to biotechnology and theranostic applications.

Focusing on one such virus—bacteriophage lambda— Carlos E. Catalano discusses the path from fundamental biological research to the development of nano-theranostics. The biology of lambda, the tools developed to faithfully recapitulate the lambda assembly reactions in vitro, and the observations that have led to co-optation of the lambda system as a “designer” nanoparticle are described.

The lambda capsid can be decorated with multiple ligands in a rigorously defined manner to allow presentation of both biological and synthetic ligands. Simultaneously, the particle can be loaded with a “cargo” (DNA, proteins, drugs) of defined composition. The lambda designer nanoparticle system is modular, tunable, and rapidly modified so that particles can be easily tailored to specific delivery and/or detection requirements, and simultaneously packaged with protein, polynucleotide, and/or synthetic cargos in a user defined manner.

This combination of features allows the engineering of semisynthetic nanoparticles specifically adapted for particle tracking, diagnostic, therapeutic, nano-bioreactor, and vaccine applications. This illustrates how a fundamental understanding of virus biology serves as a gateway to applied science, and exemplifies the concept of benchtop-to-bedside translational research.

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