ASO-Based mRNA Silencing Technology for Phage

Challenge

Understanding the function of essential genes in bacteriophages is challenging due to the lack of versatile, non-genetic tools for gene silencing, especially in complex DNA and RNA phages. Current genetic approaches are often limited, impractical, or unsuitable for regulated and industrial settings, restricting progress in phage biology, phage contamination control, and the optimization of phage therapy.

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Technology

This technology employs programmable ASOs to target specific mRNA sequences in phages, preventing the production of essential proteins. Successful experiments with the ΦKZ phage demonstrated the ability to identify and silence key genes, revealing new insights into phage biology and host-pathogen interactions. The method is also effective in studying host defense systems, even in genetically intractable strains. Furthermore, repressing of repressors of lytic phages is a possible application. This leads to the production of large numbers of lytic phages, which cause lysis of the bacterial host and could therefore be used to treat infected patients. In addition, phage production for biotechnological processes can be optimized by the repression of repressors.

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Commercial Opportunity

The technology has broad commercial potential in phage therapy, biotechnology research, pharmaceutical applications, and industrial processes. The technology is available for in-licensing and co-development.

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Development Status

Currently, the technology is at the experimental validation stage, with successful proof-of-concept studies completed. Further development is needed to optimize ASO delivery and expand its application.

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Patent Situation

A European patent application was filed in July 2024 and a PCT application in July 2025. 

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Further Reading

Gerovac, M., Buhlmann, L., Zhu, Y. et al. Programmable antisense oligomers for phage functional genomics. Nature (2025). doi.org/10.1038/s41586-025-09499-6 

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