In recent years, a growing body of research has linked the complex microbial ecologies that inhabit our bodies to diseases ranging from obesity to cancer. However, the ability to directly test hypotheses and to treat microbiome imbalances is hindered by the limited tools we have to manipulate these systems. Broad spectrum antibiotics that wipe out half of our gut flora and fecal transplants (transplantation of fecal bacteria from a healthy subject to a patient’s gut) are akin to conducting heart surgery with a shotgun or weeding your garden with gasoline.
Eligo Bioscience is here to change that.
The French startup spun out of MIT and Rockefeller last year, where cofounders developed highly precise antimicrobials. The novelty of these therapeutics is how easily they can be targeted to the bug of your choice. Eligo’s technology is based on CRISPR/Cas9, the trendy and invaluable molecular tool for making sequence-specific cuts in DNA. Cas9 is a nuclease that binds a small guide RNA (sgRNA). The nuclease will cleave DNA if, and only if, it encounters DNA with a sequence complementary to its guide RNA. Rewriting the guide RNA readily repurposes Cas9 to target new DNA sequences.
CRISPR as the new generation of antimicrobials
So what does everyone’s favorite genome editing tool have to do with antimicrobials? In the labs of Timothy Lu and Luciano Marraffini, two of the leading experts in CRISPR, cofounders Xavier Duportet and David Bikard realized they could use sequence-targeting to eliminate a single bacterial species from our rich internal ecosystems. In the gut, it can be difficult to differentiate friend from foe, because pathogens, like Shigella and Salmonella, are often closely related to beneficial flora, like E. coli. The small differences that do exist, however, are encoded in DNA that can be targeted with Cas9.
The founders of Eligo have constructed bacteriophage particles packed with Cas9 and guide RNAs to target specific genes in specific bacteria. The phage injects this package with little discrimination into a broad range of bacteria, but most bacteria will experience no effect. However, if the target gene is present, the guide RNA will bind, Cas9 will cut the genome, and the bacterium will die. So far they’ve used this groundbreaking technology to target the methicillin resistance gene in Staphylococcus aureus, and the carbapenem resistance genes in enterohemorrhagic Escherichia coli, singling out these deadly pathogens and killing them.
These preliminary demonstrations are impressive, but the true power of Eligo’s technology is the modularity and rapid prototyping of the CRISPR/Cas9 system. With the steady rise of antibiotic resistance and challenges of antibiotic development, there is a vital need for antimicrobials that can kill the current and future resistant pathogens. Small molecule development pipelines are slow and expensive, and any new antimicrobial faces the harsh reality that resistance will arise at some rate. Eligo’s technology is poised not only to target emerging superbugs, but to rapidly adapt as pathogens learn to resist it.
Eligo Bioscience also plans to combat diseases caused by microbiome disturbance. “New evidence is exposed every day that the microbiome plays a major role in our health and that it is as critical to take care of it as any other organ of our body,” says Dr. Duportet, Eligo’s CEO.
We believe that Eligo technology will not only enable the development of next-generation drugs for the treatment of infectious diseases but also the design of new tools for precise microbiome engineering to combat imbalances associated with inflammatory diseases such as IBD or acne.
Last week, the value of Eligo was recognized by Seventure, who invested €2 in seed round financing. Sebastien Groyer, a partner at Seventure and new board member for Eligo, expressed his confidence in the young company:
Its products have the potential to dramatically change the way in which we treat multiple infectious diseases while contributing to the understanding of others.
Angel investors will join the seed round this summer, before Eligo moves out of an incubator at Paris’ Institut Pasteur and into it’s own lab space.
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