Researchers at the Helmholtz Institute for RNA-based Infection Research (HIRI) and the Institute of Molecular Infection Biology (IMIB) have developed a new RNA-based method to investigate bacteriophage biology. Bacteriophages, or phages, are viruses that infect bacteria and rely on host machinery to replicate, eventually causing the bacterial cell to burst. Understanding this interaction is increasingly important as phages gain attention as possible tools against antibiotic-resistant infections.
The team, led by Jörg Vogel, applied antisense oligomers (ASOs) short synthetic strands of RNA that can bind to messenger RNA (mRNA) and block protein production. By designing ASOs to target specific phage transcripts, the researchers were able to interrupt the synthesis of proteins critical for phage replication. This approach effectively “hacked” the phage life cycle and revealed new insights into which phage proteins are essential for successful infection.
One focus of the work was the jumbo phage ΦKZ, which infects Pseudomonas aeruginosa, a major pathogen in clinical settings. By applying ASOs, the team reduced replication of ΦKZ and other phages in different bacterial hosts, showing the method’s versatility across systems.
The study demonstrates that programmable ASOs can serve as a powerful functional genomics tool, enabling systematic probing of phage genes and their roles in infection. Beyond advancing basic understanding of phage biology, this strategy may help in developing phage-based therapies or in designing ways to disrupt harmful phage-bacteria interactions.
Image credit: Nature (2025). DOI: 10.1038/s41586-025-09499-6
Article can be accessed on: Medical Express
