Cell-free expression and synthesis of viruses and bacteriophages: applications to medicine and nanotechnology

The efficacy of cell-free gene expression (CFE) has been considerably improved in the last decade. As a consequence, CFE systems have now the capacity to express DNAs composed of tens of genes encoding for complex self-assembly processes. A recent example is a demonstration that infectious bacteriophages can be synthesized in one-pot CFE reactions from their genomes. This landmark result opens new perspectives for producing in vitro large biological systems from natural or synthetic DNA. In this article, we review the recent progress in the synthesis and self-assembly of viruses in one-pot CFE reactions, primarily covering bacteriophages. We discuss the advantages and potential of producing virus-like particles and phages in CFE systems for biomedical applications. Because they are the most abundant and diverse life forms on Earth, dynamically synthesizing whole or parts of bacteriophages in test tubes could facilitate uncovering novel biological functions and exploiting their self-assembly properties for material sciences applications.