Phage engineering: how advances in molecular biology and synthetic biology are being utilized to enhance the therapeutic potential of bacteriophages

Abstract

Background: The therapeutic potential of bacteriophages has been debated since their first isolation and characterisation in the early 20^th century. However, a lack of consistency in application and observed efficacy during their early use meant that upon the discovery of antibiotic compounds research in the field of phage therapy quickly slowed. The rise of antibiotic resistance in bacteria and improvements in our abilities to modify and manipulate DNA, especially in the context of small viral genomes, has led to a recent resurgence of interest in utilising phage as antimicrobial therapeutics.

Results: In this article a number of results from the literature that have aimed to address key issues regarding the utility and efficacy of phage as antimicrobial therapeutics utilising molecular biology and synthetic biology approaches will be introduced and discussed, giving a general view of the recent progress in the field.

Conclusions: Advances in molecular biology and synthetic biology have enabled rapid progress in the field of phage engineering, with this article highlighting a number of promising strategies developed to optimise phages for the treatment of bacterial disease. Whilst many of the same issues that have historically limited the use of phages as therapeutics still exist, these modifications, or combinations thereof, may form a basis upon which future advances can be built. A focus on rigorous in vivo testing and investment in clinical trials for promising candidate phages may be required for the field to truly mature, but there is renewed hope that the potential benefits of phage therapy may finally be realised.

Graphical abstract

Keywords

bacteriophage / phage therapy / phage engineering / synthetic biology

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ACKNOWLEDGMENTS

This work was supported by the Bill and Melinda Gates Foundation under the Grand Challenges Explorations grant (OPP1139488).

COMPLIANCE WITH ETHICS GUIDELINES

The authors Russell Brown, Andreas Lengeling and Baojun Wang declare that they have no conflict of interests.

This article does not contain any studies with human or animal subjects performed by any of the authors.

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