Synthetic engineering and biological containment of bacteriophages

The serious threats posed by drug-resistant bacterial infections and recent developments in synthetic biology have fueled a growing interest in genetically engineered phages with therapeutic potential. To date, many investigations on engineered phages have been limited to proof of concept or fundame...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 119; no. 48; p. e2206739119
Main Authors Mitsunaka, Shoichi, Yamazaki, Kohei, Pramono, Ajeng K, Ikeuchi, Megumi, Kitao, Tomoe, Ohara, Naoya, Kubori, Tomoko, Nagai, Hiroki, Ando, Hiroki
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 29.11.2022
Subjects
Bacteria
Bacterial diseases
Bacterial infections
Bacterial Infections - therapy
Bacteriophages - genetics
Biological Sciences
Biology
Containment of Biohazards
Drug resistance
Genetic engineering
Genomes
Gram-negative bacteria
Humans
Infections
Phage display
Phage Therapy
Phages
Sepsis
Synthetic Biology
biological containment
synthetic biology
cell-free genome engineering
bacteriophage
phage therapy
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Summary:The serious threats posed by drug-resistant bacterial infections and recent developments in synthetic biology have fueled a growing interest in genetically engineered phages with therapeutic potential. To date, many investigations on engineered phages have been limited to proof of concept or fundamental studies using phages with relatively small genomes or commercially available "phage display kits". Moreover, safeguards supporting efficient translation for practical use have not been implemented. Here, we developed a cell-free phage engineering and rebooting platform. We successfully assembled natural, designer, and chemically synthesized genomes and rebooted functional phages infecting gram-negative bacteria and acid-fast mycobacteria. Furthermore, we demonstrated the creation of biologically contained phages for the treatment of bacterial infections. These synthetic biocontained phages exhibited similar properties to those of a parent phage against lethal sepsis in vivo. This efficient, flexible, and rational approach will serve to accelerate phage biology studies and can be used for many practical applications, including phage therapy.
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Edited by Martin J. Loessner, Eidgenossische Technische Hochschule Zurich, Zurich, Switzerland; received April 18, 2022; accepted October 11, 2022 by Editorial Board Member Richard P. Novick
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2206739119