Enhancing phage therapy through synthetic biology and genome engineering

2020/12/11 by Bryan R. Lenneman, Bryan R Lenneman, Jonas Fernbach +5 · 2 citations
Agricultural and Biological Sciences · Biochemistry, Genetics and Molecular Biology · Environmental Science · #Bacteriophages and microbial interactions #CRISPR and Genetic Engineering #Plant Virus Research Studies

paper · doi:10.1016/j.copbio.2020.11.003

openalex publication_date 2020/12/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30

Abstract

The antimicrobial and therapeutic efficacy of bacteriophages is currently limited, mostly due to rapid emergence of phage-resistance and the inability of most phage isolates to bind and infect a broad range of clinical strains. Here, we discuss how phage therapy can be improved through recent advances in genetic engineering. First, we outline how receptor-binding proteins and their relevant structural domains are engineered to redirect phage specificity and to avoid resistance. Next, we summarize how phages are reprogrammed as prokaryotic gene therapy vectors that deliver antimicrobial 'payload' proteins, such as sequence-specific nucleases, to target defined cells within complex microbiomes. Finally, we delineate big data- and novel artificial intelligence-driven approaches that may guide the design of improved synthetic phage in the future.

Citations

• Phage Therapy in the Twenty-First Century: Facing the Decline of the Antibiotic Era; Is It Finally Time for the Age of the Phage?

Cited by

• Microbes as medicine
• PHEIGES, all-cell-free phage synthesis and selection from engineered genomes

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