Treating and preventing E coli infections
AssigneeSNIPR Biome ApS
InventorsJakob Krause Haaber, Szabolcs Semsey, Mette Grove, Birgitte Damholt, Dziuginta Jasinskyte, Yilmaz Emre Gençay
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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.
Claims31
A method for treating or preventing an infection by Escherichia coli (E. coli) cells in a human or animal subject, wherein the method comprises administering a plurality of transduction particles to the subject, wherein
- (a) each transduction particle comprises a nucleic acid encoding a Cas nuclease and a nucleic acid encoding a crRNA or guide RNA that is operable with the Cas nuclease for targeting the genomes of E. coli cells,
- wherein (i) each transduction particle is a phage and the nucleic acid encoding the Cas nuclease is integrated into the genome of the phage, or (ii) each transduction particle is a phage capsid and the nucleic acid encoding the Cas nuclease is a phagemid contained in the phage capsid,
- wherein the administered transduction particles contact the cells and introduce therein the nucleic acid, wherein the Cas nuclease is expressed in the cells and cuts genomic DNA of the cells, thereby killing the cells or reducing growth or proliferation of the cells in the subject;
- (b) the E. coli cells are cells of E. coli phylogroup B2;
- and
- (c) wherein the plurality of transduction particles comprises a first type of transduction particle and a second type of transduction particle, wherein the first type of transduction particle comprises a first adhesion moiety that is capable of recognizing and binding to LPS displayed on the surface of phylogroup B2 E. coli cells, and the second type of transduction particle comprises a second adhesion moiety that is capable of recognizing and binding to Tsx displayed on the surface of phylogroup B2 E. coli cells.
A method for treating or preventing an infection by Escherichia coli (E. coli) cells in a human or animal subject, wherein the method comprises administering a plurality of transduction particles to the subject, wherein
- (a) each transduction particle comprises a nucleotide sequence (N1) encoding a Cas nuclease for targeting the genomes of E. coli cells and a nucleic acid encoding a crRNA or guide RNA that is operable with the Cas nuclease for targeting the genomes of E. coli cells,
- wherein the administered transduction particles contact the cells and introduce therein the nucleic acid, wherein the Cas nuclease is expressed in the cells and cuts genomic DNA of the cells, thereby killing the cells or reducing growth or proliferation of the cells in the subject;
- (b) the E. coli cells are cells of E. coli phylogroup B2;
- and
- each transduction particle comprises an adhesion moiety recognizing and binding to a cognate moiety selected from the group consisting of a LPS, LamB and Tsx displayed on the surface of phylogroup B2 E. coli cells,
- wherein each transduction particle is a synthetic T-even phage comprising an insertion of N1 into the genome of the phage, wherein the insertion is between a pin (protease inhibitor) gene and an iPII (internal protein) gene.
A method for treating or preventing an infection by E. coli cells in a human or animal subject, the method comprising administering to the subject a plurality of transduction particles, wherein
- (a) each transduction particle comprises a nucleic acid encoding a crRNA or guide RNA that is operable with a Cas nuclease for chromosomal targeting in the cells,
- wherein (i) each transduction particle is a phage and the nucleic acid encoding the crRNA or guide RNA is integrated into the genome of the phage, or (ii) each transduction particle is a phage capsid and the nucleic acid encoding the crRNA or guide RNA is a phagemid contained in the phage capsid,
- wherein the administered transduction particles contact the cells and introduce therein the nucleic acid, wherein the crRNA or guide RNA is expressed and guides the Cas nuclease, wherein the nuclease cuts the chromosomes of the cells, thereby killing the cells or reducing growth or proliferation of the cells in the subject;
- (b) the E. coli cells are cells of E. coli phylogroup B2;
- and
- (c) wherein the plurality of transduction particles comprises a first type of transduction particle and a second type of transduction particle, wherein the first type of transduction particle comprises a first adhesion moiety that is capable of recognizing and binding to LPS displayed on the surface of B2 E. coli cells, and the second type of transduction particle comprises a second adhesion moiety that is capable of recognizing and binding to Tsx displayed on the surface of phylogroup B2 E. coli cells.
Dependencies are inferred from the claim text.