Phage design and directed evolution to evolve phage for therapy

Prog Mol Biol Transl Sci. 2023:200:103-126. doi: 10.1016/bs.pmbts.2023.03.019. Epub 2023 Jun 19.

Abstract

Phage therapy or Phage treatment is the use of bacteriolysing phage in treating bacterial infections by using the viruses that infects and kills bacteria. This technique has been studied and practiced very long ago, but with the advent of antibiotics, it has been neglected. This foregone technique is now witnessing a revival due to development of bacterial resistance. Nowadays, with the awareness of genetic sequence of organisms, it is required that informed choices of phages have to be made for the most efficacious results. Furthermore, phages with the evolving genes are taken into consideration for the subsequent improvement in treating the patients for bacterial diseases. In addition, direct evolution methods are increasingly developing, since these are capable of creating new biological molecules having changed or unique activities, such as, improved target specificity, evolution of novel proteins with new catalytic properties or creation of nucleic acids that are capable of recognizing required pathogenic bacteria. This system is incorporates continuous evolution such as protein or genes are put under continuous evolution by providing continuous mutagenesis with least human intervention. Although, this system providing continuous directed evolution is very effective, it imposes some challenges due to requirement of heavy investment of time and resources. This chapter focuses on development of phage as a therapeutic agent against various bacteria causing diseases and it improvement using direct evolution of proteins and nucleic acids such that they target specific organisms.

Keywords: CAVE; PACE; Phage therapy; antibiotic resistance; bacterial resistance; continuous evolution; directed evolution.

MeSH terms

  • Anti-Bacterial Agents
  • Bacteriophages* / genetics
  • Catalysis
  • Humans
  • Mutagenesis
  • Nucleic Acids*

Substances

  • Anti-Bacterial Agents
  • Nucleic Acids