In a major scientific advancement, Eligo Bioscience has successfully achieved in vivo bacterial genome editing, marking a significant milestone in the field of microbial gene therapy. Published in the journal Nature, Eligo's work demonstrates for the first time the ability to precisely and efficiently edit the genomes of bacteria directly within the gut, achieving nearly 100% efficiency without disturbing surrounding microbial communities.

This development paves the way for new treatments targeting microbiome-associated diseases. While gene therapies have progressed since the 1970s, culminating in the approval of CRISPR-based drugs, the vast array of genes within the human microbiome has remained largely inaccessible until now. The microbiome, consisting of billions of commensal bacteria, plays a crucial role in our health and immune system. However, an increasing number of bacterial genes have been linked to chronic diseases, autoimmune disorders, infections, tumors, and neurodegenerative conditions. Non-targeted therapeutics affecting microbiome composition can cause serious side effects, highlighting the need for targeted microbiome editing approaches.

"What Eligo Bioscience has achieved shows that it’s now possible to make specific changes to the DNA of bacteria in the gut, similar to how scientists have been editing human genes to investigate or treat genetic disorders," said David Bikard, co-founder of Eligo Bioscience and researcher at the Institut Pasteur in Paris.

Eligo's breakthrough involves engineering, producing, and purifying a bacteriophage-derived capsid containing a synthetic DNA payload encoding a base-editor system. When administered orally to mice, the capsid delivered the payload with extreme precision to target specific bacterial populations in the gut. The system effectively inactivated antibiotic resistance genes or virulence factors by inducing single-base pair mutations. In experiments targeting E. coli strains in the mouse gut, the technology modified the target gene in over 90% of the bacteria, reaching up to 99.7% in some cases, with modifications remaining stable for at least 42 days.

Jesus Fernandez, Eligo's VP of Technology and senior author of the study, highlighted the significance of this achievement: "This achievement is the culmination of eight years of work by the team at Eligo Bioscience and represents a paradigm shift in microbiome research. This leap forward provides Eligo with a unique edge to develop microbial genetic medicines, and also to find novel therapeutic targets with a novel tool to interrogate the role and function of bacterial genes in health and disease."

Eligo Bioscience is already applying this patented approach to create new treatments for various conditions affecting millions worldwide. Xavier Duportet, CEO and co-founder of Eligo, emphasized the potential impact: "This technology enhances Eligo's pioneering arsenal of in-vivo editing tools, and can be applied to various bacteria and genes, opening the door to treatments for a wide range of health issues. ‘It therefore broadens the landscape of addressable therapeutic targets in the gene editing field’.

‍