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