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-11788085-B2
Publication Date
2023-10-17
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
The disclosed invention relates to treating or reducing the risk of a urinary tract infection caused by first bacteria in a subject by selectively killing the first bacteria. Selective killing is achieved by cutting a target site comprised by the genomes of the first bacteria using an RNA-guided Cas nuclease, with one or more guide RNAs that hybridize to the target site to guide the Cas nuclease to cut the target site and thereby kill the first bacteria.
The subject comprises second bacteria of one or more strains or species different from that of the first bacteria, and the genomes of the second bacteria do not comprise the target site. The genomes of the second bacteria 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 invention also specifies administering a nucleic acid sequence comprising or encoding one or more gRNAs at a first time (T1) and at a second time (T2), where T2 is at least 3 hours after T1. Performance is defined quantitatively by reducing the number of the first bacteria at least 100-fold by the first 30 minutes after exposing the subject to the one or more gRNAs, or maintaining reduction by at least 100-fold for at least 60 minutes after exposing the subject to the one or more gRNAs.
Claims Coverage
The partial record includes two independent claims. Across these claims, the inventive coverage centers on selective treatment of urinary tract infections by RNA-guided Cas nuclease cutting of a genomic target site, with gRNA administration at T1 and T2 separated by at least 3 hours and with quantitative reduction or maintained reduction of the first bacteria.
Selective genomic target cutting for urinary tract infection treatment
A method of treating or reducing the risk of a urinary tract infection caused by first bacteria by selectively killing the first bacteria in the subject by cutting a target site comprised by the genomes of the first bacteria using an RNA-guided Cas nuclease.
Time-separated administration of gRNA-encoding nucleic acid
Administering to the subject a nucleic acid sequence comprising or encoding one or more guide RNAs at a first time (T1) and at a second time (T2), wherein T2 is at least 3 hours after T1.
Non-target bacterial survival based on absence of target site
The subject comprises second bacteria of one or more strains or species different from that of the first bacteria, wherein the genomes of the second bacteria do not comprise the target site, wherein the genomes of the second bacteria are not cut by the Cas nuclease in the subject, whereby second bacteria survive in the presence of the Cas nuclease in the subject.
Rapid reduction of first-bacteria numbers
The number of the first bacteria is reduced at least 100-fold by the first 30 minutes after exposing the subject to the one or more gRNAs.
Sustained reduction of first-bacteria numbers
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 one or more gRNAs.
Across the independent claims, the core claimed coverage centers on RNA-guided Cas nuclease cutting of a genomic target site in first bacteria to treat or reduce the risk of urinary tract infection, while second bacteria survive because they lack the target site. The claims also require gRNA administration at T1 and T2 with T2 at least 3 hours after T1, together with a quantitative reduction limitation.
Stated Advantages
Selective killing of first bacteria by cutting a genomic target site using an RNA-guided Cas nuclease.
Second bacteria survive in the presence of the Cas nuclease when their genomes do not comprise the target site.
Reducing the number of the first bacteria by at least 100-fold by the first 30 minutes after exposing the subject to the one or more gRNAs.
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 one or more gRNAs.
Documented Applications
Treating or reducing the risk of a urinary tract infection caused by first bacteria in a subject.
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