Treating and preventing microbial infections
Inventors
Sommer, Morten • MARTINEZ, Virginia • VAN DER HELM, Eric • HAABER, Jakob Krause • DE SANTIAGO TORIO, Ana • Grøndahl, Christian • Clube, Jasper
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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-11643653-B2
Publication Date
2023-05-09
Expiration Date
Abstract
The invention provides methods for treating or preventing microbial (eg, bacterial) infections and means for performing these methods. In particular, treatment of infections requiring rapid and durable therapy is made possible, such as for treating acute conditions such as septicemia, sepsis, SIRS or septic shock. The invention is particularly useful, for example, for treatment of microbes such as for environmental, food and beverage use. The invention relates inter alia to methods of controlling microbiologically influenced corrosion (MIC) or biofouling of a substrate or fluid in an industrial or domestic system. The invention also useful for the treatment of pathogenic bacterial infections in subjects receiving a treatment for a disease or condition, such as a transplant or a treatment for cancer, a viral infection or an autoimmune disease.
Core Innovation
A method is described for selectively killing first bacteria in a subject by cutting a target site comprised by the genomes of the first bacteria, where the cutting is carried out using a Cas nuclease programmed by a guide RNA (gRNA) to cut the target site. The target site is located in a pks gene, and the first bacteria are pks positive Escherichia coli (E. coli).
The subject further comprises second bacteria of one or more strains or species different from the first bacteria, where the genomes of the second bacteria do not comprise the target site and are not cut by the Cas nuclease in the subject, whereby the second bacteria survive in the presence of the Cas nuclease in the subject. The approach is framed around genome-targeted cutting at a gene-containing target site using a gRNA-programmed Cas nuclease, while relying on absence of the target site in non-target bacteria to preserve them.
The method further includes reducing the number of the first bacteria at least 100-fold by the first 30 minutes after exposing the subject to the Cas nuclease and/or the gRNA, and maintaining a reduction in the number of the first bacteria by at least 100-fold for at least 60 minutes after exposing the subject to the Cas nuclease and/or the guide RNA. Implementation is specified to use a Cas nuclease selected from Cpf1, Cas9, or Cas3, and the gRNA can include a sequence that hybridizes to a protospacer sequence at the target site.
Claims Coverage
Two independent claims are present. Across these independent claims, the coverage centers on genome-targeted Cas nuclease cutting programmed by a guide RNA at a pks gene target site in pks-positive E. coli, while sparing different second bacteria lacking the target site, together with specified timing and magnitude reduction requirements.
Selective killing using gRNA-programmed Cas nuclease targeting a pks gene
Selectively killing first bacteria in a subject by cutting a target site comprised by the genomes of the first bacteria, wherein the cutting is carried out using a Cas nuclease that is programmed by a guide RNA (gRNA) to cut the target site, wherein the target site is in a pks gene and the first bacteria are pks positive Escherichia coli (E. coli), and wherein the subject comprises second bacteria of one or more strains or species different from that of the first bacteria, where the genomes of the second bacteria do not comprise the target site and are not cut by the Cas nuclease in the subject, whereby second bacteria survive.
Rapid 100-fold reduction within first 30 minutes
Reducing the number of the first bacteria at least 100-fold by the first 30 minutes after exposing the subject to the Cas nuclease and/or the gRNA.
Maintained 100-fold reduction for at least 60 minutes
Maintaining reduction in the number of the first bacteria by at least 100-fold for at least 60 minutes after exposing the subject to the Cas nuclease and/or the guide RNA.
The independent claims require Cas nuclease cutting directed by a guide RNA to a pks gene target site in pks-positive E. coli, non-cutting and survival of different second bacteria lacking that target site, and specified first-bacteria reduction kinetics.
Stated Advantages
Second bacteria survive in the presence of the Cas nuclease in the subject because their genomes do not comprise the target site.
A reduction in the number of the first bacteria at least 100-fold is achieved by the first 30 minutes after exposing the subject to the Cas nuclease and/or the gRNA.
The reduction in the number of the first bacteria is maintained at least 100-fold for at least 60 minutes after exposing the subject to the Cas nuclease and/or the guide RNA.
Selective killing of first bacteria while allowing second bacteria that lack the target site to survive.
Documented Applications
A method of selectively killing first bacteria in a subject.
Concurrently administering therapy for a further disease/condition, notably cancer immunotherapy, together with precision genome-targeted nuclease killing of pathogenic bacteria.
Microbiome-related applications that involve maintaining therapy efficacy in the presence of second bacteria that do not have the nuclease target site.
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