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Phage engineering: how advances in molecular biology and synthetic biology are being utilized to enhance the therapeutic potential of bacteriophages |
Russell Brown1,2,Andreas Lengeling3,Baojun Wang1,2( ) |
1. School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FF, UK
2. Centre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh, EH9 3FF, UK
3. Infection and Immunity Division, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK |
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Abstract Background: The therapeutic potential of bacteriophages has been debated since their first isolation and characterisation in the early 20th 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.
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Author Summary A bacteriophage (phage) is a virus that infects and replicates within bacteria, often leading to bacterial lysis and death. Phages that are able to efficiently kill specific bacterial pathogens have long been identified as having therapeutic potential in the context of treating bacterial disease in animals and humans; however the efficacies of phage therapies have rarely reached those of antibiotic drugs. This article aims to summarise recent developments in the field of phage engineering, where the tools of molecular biology and synthetic biology are being used to modify phages in ways that enhance or alter their natural antimicrobial function. |
Keywords
bacteriophage
phage therapy
phage engineering
synthetic biology
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Fund: |
Corresponding Author(s):
Baojun Wang
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Issue Date: 22 March 2017
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