Jesus Fernandez-Rodriguez: How Eligo Bioscience edits gut bacteria with phages

Welcome to the Podovirus podcast, episode 3! In this episode, I talk with Jesus Fernandez-Rodriguez from Eligo Bioscience, a Paris-based biotech company pioneering microbiome editing using modified bacteriophages. We talk about Eligo’s recent Nature publication, “In situ targeted base editing of bacteria in the mouse gut”, how it works, and what the team is thinking of doing with it. 💡 Takeaways: - Eligo Biosciences has developed a base editing technology using modified phages to precisely modify populations of E. coli and Klebsiella in the mouse gut microbiome without killing them. - Microbiome hype is not over yet! - Beyond using the editing tool to kill bacteria for therapeutic reasons, this tool can be used to delete a gene or bacterium to probe what happens in vivo, which could help us figure out what to try to drug next - Not all targets need to be infectious disease-based: the gut-brain axis is an interesting area that this approach could be useful for (or any bacteria-causing disease or phenotype) - The Eligo team designed their base editing system using a PICI (phage-inducible chromosomal island) origin of replication, which lets them produce their therapeutic 'cosmid' (plasmid containing lambda phage packaging instructions plus their payload) in an E. coli strain expressing PICI primase, but prevents replication of the cosmid in target bacteria. 📕 Read: Eligo's In Situ Base Editing paper, published July 2024 in Nature: https://www.nature.com/articles/s41586-024-07681-w 💻 Check out Eligo Bioscience's website, especially their open roles! https://eligo.bio/ Chapters 00:00 Introduction to Eligo Biosciences and their work 02:22 History and evolution of Eligo Biosciences' technology 03:23 Transition from antimicrobial focus to microbiome editing 05:21 Base editing, killing bacteria, and modifying bacteria 06:11 The importance of understanding and targeting bacterial genes in human disease 11:30 Distinguishing base editing from CRISPR and its applications 13:27 Different tools for different modifications in bacteria 16:16 Engineering phage particles for high transduction efficiencies 21:33 Challenges and process of publishing the paper 23:29 The value of publishing and attracting talent 27:19 Eligo Biosciences' plans for clinical trials and future applications 28:43 The importance of bacterial genes in human disease and the new way of thinking 29:12 Microbiome Research and Gut-Brain Axis 31:34 Challenges in Identifying Microbes and Genes 34:48 The PICI System in Eligo's Technology 37:14 Multiplexing the Base Editing Approach 52:04 Complexity of Identifying Disease-Causing Genes 56:25 The Importance of Research and Collaboration