ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Antibiotic Resistance and New Antimicrobial drugs
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1561443
This article is part of the Research TopicAdvances in Bacteriophage Research & Development with Therapeutic ApplicationsView all 6 articles
High-yield bioproduction of virus-free virus-like P4-EKORhE multi-lysin transducing particles as an antimicrobial gene therapeutic
Provisionally accepted
- 1Monash-Warwick Alliance Joint Doctoral Programme, United Kindgom, Australia
- 2School of Life Sciences, Faculty of Science, Engineering and Medicine, The University of Warwick, Coventry, United Kingdom
- 3School of Biological Sciences, Faculty of Sciences, Monash University, Clayton, Melbourne, Australia
- 4Department of Computing, Faculty of Engineering, Imperial College London, London, England, United Kingdom
- 5SynbiCITE, Innovation and Translation Hub, Imperial College London, London, United Kingdom
- 6ACGTx, London, United Kingdom
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A description of the construction of the bioengineered P4-EKORhE and a comprehensive method for producing very high yields (up to 10\textsuperscript{12} particles per millilitre) enable the use of virus-like particles to transduce genetically encoded antimicrobials through a combination of synthetic biology and optimised upstream and downstream processing. The final product, a gene-delivered antimicrobial in the form of the multi-lysins cassette, is fully functional before and after packaging within P4-EKORhE particles. The antimicrobial activity of the multi-lysins cassette, characterised by its lysis proteins, was tested \textit{in vivo} in both pure bacterial \textit{Escherichia coli} (\textit{E. coli}) cultures and in a model of phage infection in co-culture with A549 immortalised human epithelial tissue cells. This work exemplifies several bioproduction methods and demonstrates how the virology of the P4 and P2 phages can be harnessed to establish a bioprocess for producing transducing particles at very high yields, avoiding contamination by the natural virus while maintaining the antimicrobial effectiveness of the final product.
Keywords: high-yield bioproduction, Bioprocess engineering, Virus-like particles, Transducing particles, antimicrobials, Gene therapeutics, A549-model of infection, P4-EKORhE
Received: 15 Jan 2025; Accepted: 14 May 2025.
Copyright: © 2025 Ramirez-Garcia, Sagona and Barr. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Robert Ramirez-Garcia, Monash-Warwick Alliance Joint Doctoral Programme, United Kindgom, Australia
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