RRC ID 74401
著者 Shoichi Mitsunaka, Kohei Yamazaki, Ajeng K. Pramono, Megumi Ikeuchi, Tomoe Kitao, Naoya Ohara, Tomoko Kubori, Hiroki Nagai, Hiroki Ando
タイトル Synthetic engineering and biological containment of bacteriophages
ジャーナル Proceedings of the National Academy of Sciences
Abstract 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.
巻・号 119
公開日 2022-11-29
DOI 10.1073/pnas.2206739119
PMID 36409909
PMC PMC9860248
MeSH Bacterial Infections* / therapy Bacteriophages* / genetics Containment of Biohazards Humans Phage Therapy* Synthetic Biology
リソース情報
原核生物(大腸菌) ME9062