Treating and preventing E coli infections
Inventors
HAABER, Jakob Krause • SEMSEY, Szabolcs • Grove, Mette • DAMHOLT, Birgitte • Jasinskyte, Dziuginta • Gençay, Yilmaz Emre
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Assignees
MemberSNIPR BiomeSNIPR BiomeSNIPR Biome develops precision medicines for infections and diseases linked to antimicrobial resistance and microbiome dysbiosis, using CRISPR-based gene editing to selectively target pathogenic bacteria while sparing the rest of the microbial community. The company applies programmable CRISPR platforms, delivered by engineered phages or probiotics, to address difficult-to-treat infections and modulate the human microbiome. Its programs span discovery through Phase 2 clinical trials, with a significant patent portfolio supporting these innovations.
SNIPR Biome develops precision medicines for infections and diseases linked to antimicrobial resistance and microbiome dysbiosis, using CRISPR-based gene editing to selectively target pathogenic bacteria while sparing the rest of the microbial community. The company applies programmable CRISPR platforms, delivered by engineered phages or probiotics, to address difficult-to-treat infections and modulate the human microbiome. Its programs span discovery through Phase 2 clinical trials, with a significant patent portfolio supporting these innovations.
Publication Number
US-12076375-B2
Publication Date
2024-09-03
Expiration Date
Abstract
The invention relates to methods and compositions for treating or preventing an infection by E coli cells in human or animal subjects. The method comprises administering to the subject a plurality of transduction particles that encode a nuclease for targeting the genomes of B2 phylogroup E coli cells.
Core Innovation
The invention provides a method for treating or preventing an infection by Escherichia coli (E. coli) cells in a human or animal subject. The method administers a plurality of transduction particles that contact the cells and introduce nucleic acid into the cells. The introduced nucleic acid encodes a Cas nuclease and a crRNA or guide RNA operable with the Cas nuclease for targeting genomes or chromosomes of E. coli cells.
The Cas nuclease is expressed in the cells and cuts genomic DNA or chromosomes of the cells, thereby killing the cells or reducing growth or proliferation of the cells in the subject. The E. coli cells are cells of E. coli phylogroup B2, thereby linking targeting activity to phylogroup B2 cells. The transduction particles are configured as phage or phage capsid systems, including cases where the nucleic acid encoding Cas nuclease or crRNA or guide RNA is integrated into a phage genome or contained as a phagemid in a phage capsid.
To improve selective contact and delivery to phylogroup B2 cells, the plurality of transduction particles includes a first type and a second type with different adhesion moieties. The first adhesion moiety recognizes and binds to LPS displayed on the surface of phylogroup B2 E. coli cells, and the second adhesion moiety recognizes and binds to Tsx displayed on the surface of phylogroup B2 E. coli cells. In some configurations, additional particle types provide adhesion moieties recognizing and binding to LamB.
Claims Coverage
The partial content provides three independent claims. Across these independent claims, the inventive coverage is centered on phage-based transduction particles delivering Cas nuclease and guide RNA for genome or chromosome cutting in E. coli phylogroup B2, combined with adhesion-moiety targeting of B2 surface moieties (LPS, Tsx, and optionally LamB) and specified phage or phage capsid configurations.
Treating or preventing infection in human or animal subjects with phage transduction particles encoding Cas nuclease and crRNA or guide RNA for genome targeting of E. coli phylogroup B2
Administering a plurality of transduction particles to a human or animal subject for treating or preventing an infection by E. coli cells of E. coli phylogroup B2, where each particle comprises nucleic acid encoding a Cas nuclease and nucleic acid encoding a crRNA or guide RNA operable for targeting E. coli genomes; the particles contact the cells, introduce the nucleic acid, express the Cas nuclease, and cut genomic DNA to kill cells or reduce growth or proliferation, with each transduction particle being a phage or a phage capsid.
Synthetic T-even phage transduction with genome-targeting Cas nuclease and adhesion moiety binding to LPS, LamB, or Tsx on E. coli phylogroup B2
Administering a plurality of transduction particles for treating or preventing an infection by E. coli cells in a human or animal subject, where the particles comprise a nucleotide sequence encoding a Cas nuclease and nucleic acid encoding a crRNA or guide RNA for targeting E. coli genomes, the Cas nuclease is expressed in the cells and cuts genomic DNA to kill or reduce growth or proliferation, the E. coli cells are of E. coli phylogroup B2, each particle comprises an adhesion moiety recognizing and binding to a cognate moiety selected from LPS, LamB and Tsx displayed on the surface of phylogroup B2 E. coli cells, and each particle is a synthetic T-even phage.
Chromosomal targeting using phage transduction particles expressing guide RNA to direct Cas nuclease cutting of E. coli phylogroup B2 chromosomes with adhesion-moiety selection
Administering a plurality of transduction particles to treat or prevent an infection by E. coli cells in a human or animal subject, where each particle comprises nucleic acid encoding a crRNA or guide RNA operable with a Cas nuclease for chromosomal targeting in the cells; each particle is a phage or a phage capsid, the particles contact the cells and introduce the nucleic acid, the crRNA or guide RNA is expressed and guides the Cas nuclease, the nuclease cuts the chromosomes thereby killing the cells or reducing growth or proliferation, the E. coli cells are of E. coli phylogroup B2, and the plurality comprises a first type and a second type with adhesion moieties recognizing LPS and Tsx displayed on the surface of phylogroup B2 E. coli cells.
Across the independent claims, the coverage is directed to phage-based transduction particles that deliver nucleic acids for Cas nuclease expression and crRNA or guide RNA function to cut E. coli genomes or chromosomes in E. coli phylogroup B2, with selective engagement via adhesion moieties for LPS and Tsx and, in one claim, LamB. The claims further specify phage or phage capsid configurations for delivering the nucleic acids and directing chromosome cutting.
Stated Advantages
Killing E. coli cells.
Reducing growth or proliferation of E. coli cells.
Treating or preventing an infection by E. coli cells in a human or animal subject.
Documented Applications
Treating or preventing an infection by Escherichia coli (E. coli) cells in a human or animal subject.
Targeting E. coli phylogroup B2 infections using phage-based transduction particles that introduce nucleic acids and reduce or eliminate cell viability.
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