Synthetic Biology Journal ›› 2023, Vol. 4 ›› Issue (2): 283-300.doi: 10.12211/2096-8280.2022-070

• Invited Review • Previous Articles     Next Articles

Merging the frontiers: synthetic biology for advanced bacteriophage design

Qingli CHEN, Yigang TONG   

  1. College of Life Science and Technology,Beijing University of Chemical Technology,Beijing 100029,China
  • Received:2022-12-06 Revised:2022-12-30 Online:2023-04-30 Published:2023-04-27
  • Contact: Yigang TONG


Bacteriophages (phages), natural viruses known for infecting and killing bacteria, are the most diverse and abundant organisms on Earth. Within the past 100 years of research on phages, breakthroughs in genetics, molecular biology, and synthetic biology have been successfully achieved. The fascinating scientific history of phage therapy has been repeatedly reported, as drug-resistant bacteria are becoming increasingly prevalent. Although phages outnumber other species combined in nature (1031 in total), only a small fraction of them have been successfully exploited for fighting infections caused by drug-resistant bacteria. Therefore, there is an urgent need for implementing the motto of synthetic biology, "build to learn, build to use", and also using methods such as high-throughput sequencing and precise genome editing to create enhanced variants with unique features, improving efficacy and programmability for phage therapy. In the review, we discuss recent technological advances in phage genome engineering approaches and the potential applications of synthetic biology to engineer phages, such as modifying the host range of phages for practical needs, mining the extensive resources of phages in nature with the help of macro genomes, combining multi-omics technologies to reveal molecular mechanisms underlying phage-host interactions, regulating intestinal phages to maintain intestinal homeostasis for human health, and using big data and artificial intelligence to guide rational phage design. Synthetic biology is driving a paradigm shift in traditional experimental research by combining "Design-Build-Test-Learn (DBTL) cycles" to rational design for phages, making synthetically designed phages promising for both top-down system optimization and bottom-up life-form reconstruction.

Key words: phage, synthetic biology, engineered phage, reprogramming genome, rational design, phage therapy

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