Sequence specific antimicrobials
AssigneeThe Rockfeller University
InventorsDavid Bikard, Luciano Marraffini
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Abstract
Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both.
Claims14
A method for killing targeted bacteria in a mixed bacterial population comprising:
- providing a pharmaceutical composition comprising a pharmaceutically acceptable carrier and packaged, recombinant phagemids that are packaged in phage capsids,
- wherein the packaged phagemids comprise a clustered regularly interspaced short palindromic repeats (CRISPR) system,
- wherein the CRISPR system comprises DNA encoding:
- i) a type II CRISPR-associated enzyme;
- and ii) a targeting RNA that targets at least one bacterial chromosome at a target site;
- and
- contacting the bacterial population with the pharmaceutical composition,
- wherein the contacting with the pharmaceutical composition introduces at least some of the phagemids into at least some of the bacteria in the bacterial population,
- wherein subsequent to the introduction of the phagemids, the bacteria into which the phagemid is introduced expresses the targeting RNA and the type II CRISPR-associated enzyme,
- wherein the expressed type II CRISPR-associated enzyme cleaves the bacterial chromosome at the target site of the targeting RNA, and
- wherein the cleavage of the bacterial chromosome at the target site kills the bacteria;
- wherein the mixed bacterial population consists of two different strains of Staphylococcus aureus.
A method for killing targeted bacteria in a bacterial population comprising:
- providing a pharmaceutical composition comprising a pharmaceutically acceptable carrier and packaged, recombinant phagemids that are packaged in phage capsids,
- wherein the packaged phagemids comprise a clustered regularly interspaced short palindromic repeats (CRISPR) system,
- wherein the CRISPR system comprises DNA encoding:
- i) a type II CRISPR-associated enzyme;
- and ii) a targeting RNA that targets at least one bacterial chromosome at a target site;
- and
- contacting the bacterial population with the pharmaceutical composition,
- wherein the contacting with the pharmaceutical composition introduces at least some of the phagemids into at least some of the bacteria in the bacterial population,
- wherein subsequent to the introduction of the phagemids, the bacteria into which the phagemid is introduced expresses the targeting RNA and the type II CRISPR-associated enzyme,
- wherein the expressed type II CRISPR-associated enzyme cleaves the bacterial chromosome at the target site of the targeting RNA, and
- wherein the cleavage of the bacterial chromosome at the target site kills the bacteria.
A method for killing targeted bacteria in a bacterial population comprising:
- providing packaged, recombinant phagemids that are packaged in phage capsids,
- wherein the packaged phagemids comprise a clustered regularly interspaced short palindromic repeats (CRISPR) system,
- wherein the CRISPR system comprises DNA encoding:
- i) a type II CRISPR-associated enzyme;
- and ii) a targeting RNA that targets at least one bacterial chromosome at a target site;
- and
- contacting the bacterial population with the packaged, recombinant phagemids,
- wherein the contacting with packaged, recombinant phagemids introduces at least some of the phagemids into at least some of the bacteria in the bacterial population,
- wherein subsequent to the introduction of the phagemids, the bacteria into which the phagemid is introduced expresses the targeting RNA and the type II CRISPR-associated enzyme,
- wherein the expressed type II CRISPR-associated enzyme cleaves the bacterial chromosome at the target site of the targeting RNA, and
- wherein the cleavage of the bacterial chromosome at the target site kills the bacteria.
Dependencies are inferred from the claim text.