Systems for modulating microbiome target cells, methods and compositions thereof

A system for modifying target bacterial cell/s and/or target bacterial cell population to produce a product of interest, comprising:

• (a) at least one microbiome modulating component comprising:
• (i) at least one nucleic acid sequence encoding and/or modulating said at least one product of interest and/or at least one element participating in the production and/or metabolism of said at least one product of interest;
• and
• (ii) at least one cas gene and at least one Clustered, Regularly Interspaced Short Palindromic Repeat (CRISPR) array, comprising at least one spacer;
• and
• (b) at least one selective component comprising at least one protospacer, wherein said at least one protospacer is targeted by at least one spacer of the CRISPR array of (a), thereby inactivating said selective component.

A method for modifying target bacterial cell/s and/or target bacterial cell population to produce a product of interest, the method comprising at least one of:

• a) contacting said cell/s or any cell population comprising said cell/s with at least one microbiome modulating component comprising:
• (i) at least one nucleic acid sequence encoding and/or modulating at least one said product of interest and/or at least one element participating in the production and/or metabolism of said at least one product of interest;
• and
• (ii) at least one cas gene and at least one CRISPR array comprising at least one spacer;
• and
• (b) contacting said cells or any cell population comprising said cell/s with at least one selective component comprising at least one protospacer, wherein said at least one protospacer is targeted by at least one spacer of the CRISPR array of (a), such that said selective component is inactivated;
• thereby modifying target bacterial cell/s and/or target bacterial cell population to produce said product of interest.

A method for treating, preventing, ameliorating, reducing or delaying the onset of at least one pathologic disorder in a subject in need thereof, the method comprising the step of administering to said subject an effective amount of at least one of:

• (I) (a) at least one microbiome modulating component comprising:
• (i) at least one nucleic acid sequence encoding and/or modulating at least one said product of interest and/or at least one element participating in the production and/or metabolism of said at least one product of interest;
• and
• (ii) at least one cas gene and at least one CRISPR array, comprising at least one spacer;
• and
• (b) at least one selective component comprising at least one protospacer, wherein said at least one protospacer is targeted by at least one spacer of the CRISPR array of (a), thereby inactivating said selective component;
• (II) at least one bacterial cell and/or a population of said bacterial cells, or any composition or product thereof, producing said product of interest;
• (III) at least one composition, kit or system comprising at least one of (I) and (II);
• and
• (IV) any combination of said at least one of (I), (II) and (III) with at least one therapeutic agent.

A pharmaceutical composition or kit comprising at least one of:

• (I) (a) at least one microbiome modulating component comprising:
• (i) at least one nucleic acid sequence encoding and/or modulating said at least one product of interest and/or at least one element participating in the production and/or metabolism of said at least one product of interest;
• and
• (ii) at least one cas gene and at least one CRISPR array, comprising at least one spacer;
• and
• (b) at least one selective component comprising at least one protospacer, wherein said at least one protospacer is targeted by at least one spacer of the CRISPR array of (a), thereby inactivating said selective component;
• (II) at least one bacterial cell and/or a population of said bacterial cells producing said product of interest, or any product thereof;
• and
• (III) any combination of said at least one of (I) and (II), optionally, with at least one therapeutic agent, said composition or kit optionally further comprises at least one of pharmaceutically acceptable carrier/s, diluent/s, excipient/s and additive/s.