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

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 provides a method of treating or reducing the risk of an acute infection in a human or animal subject in need of a transplant or that has been administered a transplant, where the infection is caused by first bacteria of a first pathogenic species or strain of Escherichia coli. The method selectively kills the first bacteria by cutting a target site comprised by the genomes of the first bacteria, and the cutting is performed by guiding a Cas nuclease to the target site to effect genome cutting.

The method comprises administering to the subject a nucleic acid sequence comprising or encoding a guide RNA, where the guide RNA hybridizes to the target site to guide a Cas nuclease to cut the target site, thereby killing the first bacteria. The disclosed approach is applied in the context of a transplant that is a tissue, organ or stem cell transplant, and the subject-matter frames the treatment as selectively killing bacteria in a transplant recipient by genome-targeted cutting.

The disclosed teachings further define conditions under which bacteria other than the first bacteria are spared, by using genomes that do not include a target site. In particular, the method includes a sparing mechanism in which a subject containing second bacteria with genomes lacking a target site is not cut by a Cas nuclease, thereby allowing the second bacteria to survive in the presence of the Cas nuclease.

Claims Coverage

The provided material includes one independent claim describing a transplant-related treatment method using genome-targeted CRISPR cutting directed by an administered guide RNA and a Cas nuclease. The claim set centers on selective killing of first pathogenic Escherichia coli in a transplant recipient, with dependent refinements including transplant type, sparing of second bacteria lacking the target site, vector types, Cas nuclease type, and quantitative performance constraints.

The invention is directed to selectively killing first pathogenic Escherichia coli bacteria in a transplant recipient by administering a nucleic acid encoding a guide RNA that hybridizes to a genome target site and guides a Cas nuclease to cut that target site. The transplant is limited to tissue, organ or stem cell transplant, and dependent refinements include sparing second bacteria lacking the target site and specifying particular Cas nuclease or delivery vector formats.

Stated Advantages

Documented Applications