- Setting the Stage for a Successful Launch Into the Microbiome Space
- The Skin Microbiome in Relation to the Clothing Microbiome
- Microbiome host interaction: Influence of FLG Loss-Of-Function Mutations in Host-Microbe Interactions During Atopic Skin Inflammation
- Developing Beneficial Bacteria as Topical Therapeutics to Treat Skin Diseases
- How Phage Capsids Can Be Engineered for Gene Therapy of the Microbiome
- Restoring Healthy Skin Ecology with Microbial Ensembles
- Biofilm Production & Inflammatory Skin Molecules Support the Growth & Persistence of Cutibacterium acnes in Acne Vulgaris
How Phage Capsids Can Be Engineered for Gene Therapy of the Microbiome
Eligobiotics® are a first-in-class proprietary modality that enables the delivery and expression of therapeutic DNA in target bacterial populations of the microbiome. This technology allows different types of strategies of modulation of the microbiome’s composition and function to address human disease with an unprecedented precision.
The first technology used is called SSAM (Sequence-Specific Anti-Microbials)
Armed with a CRISPR system, Eligobiotics® become highly precise antimicrobials. They kill only the harmful bacteria by creating lethal DNA breaks in target sequences of their genome, while leaving the beneficial bacteria completely intact. Once the DNA payload is injected in the bacteria, the nuclease is expressed and its corresponding guide RNA will guide it toward bacterial genomic sequences homologous to the guide RNA. If such sequences are present, the nuclease will create targeted DNA double-strand breaks, leading to the death of the bacteria. If these sequences are absent from the bacteria, the nuclease won’t create any double-strand breaks, and the bacteria will be left intact.
Shiga toxin producing Escherichia coli (STEC) is a pathogenic bacterium responsible for human infections with various clinical manifestations. The first symptoms are common diarrhea or hemorrhagic colitis and can lead to hemolytic-uremic syndrome, thrombotic microangiopathy, severe neurological complications, or chronic renal failure. Early treatment with EB003 (a CRISPR based system) leads to resolution of diarrhea via the killing of 99% of STEC E. coli and the reduction of toxin production and prevents evolution into haemolytic uremic syndrome and kidney damage.
This same technology has also been tested in acne. C. acnes strains associated with acne have a different genetic signature from C. acnes strains associated with healthy skin. Pathogenic C. acnes strains belonging to ribotypes RT4 and RT5 have unique genetic elements that can be used to robustly discriminate them from healt-associated strains. A topical formulation containing CRISPR-based Eligobiotics® (EB005) is able to rebalance skin microbiome by specifici removal of pro-inflammatory C. acnes strains.
A second technology is called FAME (Function Addition to the MicrobiomE)
Eligobiotics® can be used to leverage microbial populations to transiently produce, display, or secrete an exogenous gene or set of genes to have a therapeutic effect on the host. Once the non-replicative DNA payload is injected in the bacteria, the gene(s) will be efficiently expressed to have the desired effect on the host.
To learn more: https://eligo.bio/
