Methods of depleting a target molecule from an initial collection of nucleic acids, and compositions and kits for practicing the same

A method of selectively separating one or more target nucleic acids from a composition, the method comprising:

• obtaining a composition comprising both target nucleic acids and non-target nucleic acids;
• contacting the composition with one or more cleavage-deficient nucleases that lack nuclease activity and one or more guide nucleic acids that guide the one or more cleavage-deficient nucleases to the one or more target nucleic acids to produce a contacted composition, wherein the contacted composition comprises the target nucleic acids, the non-target nucleic acids, the one or more cleavage-deficient nucleases, and the one or more guide nucleic acids, and the one or more cleavage-deficient nucleases, the one or more guide nucleic acids, and the one or more target nucleic acids form a complex in which the one or more guide nucleic acids specifically hybridize with the one or more target nucleic acids;
• and
• separating the complex from the contacted composition, thereby selectively separating the one or more target nucleic acids from the composition.