The disclosure describes novel systems, methods, and compositions for the manipulation of nucleic acids in a targeted fashion. The disclosure describes non-naturally occurring, engineered CRISPR systems, components, and methods for targeted modification of nucleic acids. Each system includes one or more protein components and one or more nucleic acid components that together target nucleic acids.

The disclosure describes novel systems, methods, and compositions for the manipulation of nucleic acids in a targeted fashion. The disclosure describes non-naturally occurring, engineered CRISPR systems, components, and methods for targeted modification of nucleic acids. Each system includes one or more protein components and one or more nucleic acid components that together target nucleic acids.

The present disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides mutated Cas13 proteins and their use in modifying target sequences as well as mutated Cas13 nucleic acid sequences and vectors encoding mutated Cas13 proteins and vector systems or CRISPR-Cas13 systems.

The present disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides mutated Cas13 proteins and their use in modifying target sequences as well as mutated Cas13 nucleic acid sequences and vectors encoding mutated Cas13 proteins and vector systems or CRISPR-Cas13 systems.

The present invention provides a use of a Cas protein, and a method and a kit for detecting target nucleic acid molecules. The method for detecting target nucleic acid molecules comprises adding a guide RNA, a Cas12a, and a nucleic acid probe into a reaction system containing target nucleic acid molecules to be detected, and detecting it after the reaction is completed.

The present invention provides a use of a Cas protein, and a method and a kit for detecting target nucleic acid molecules. The method for detecting target nucleic acid molecules comprises adding a guide RNA, a Cas12a, and a nucleic acid probe into a reaction system containing target nucleic acid molecules to be detected, and detecting it after the reaction is completed.

The present invention provides a use of a Cas protein, and a method and a kit for detecting target nucleic acid molecules. The method for detecting target nucleic acid molecules comprises adding a guide RNA, a Cas12a, and a nucleic acid probe into a reaction system containing target nucleic acid molecules to be detected, and detecting it after the reaction is completed.

Provided is a labeling method for nucleic acid including a reaction step for hybridizing a nucleic acid probe that has a nucleotide sequence complementary to that of a nucleic acid to be labeled and contains a reactive nucleobase derivative incorporated at a position complementary to that of a target nucleobase as a target of labeling in the nucleic acid to be labeled, to the nucleic acid to be labeled; a transferring step for transferring a transfer group contained in the reactive nucleobase derivative to the nucleotide residue containing the target nucleobase in the nucleic acid to be labeled; and a labeling step for labeling the transfer group transferred to the nucleotide residue with a radioactive material.

Provided is a labeling method for nucleic acid including a reaction step for hybridizing a nucleic acid probe that has a nucleotide sequence complementary to that of a nucleic acid to be labeled and contains a reactive nucleobase derivative incorporated at a position complementary to that of a target nucleobase as a target of labeling in the nucleic acid to be labeled, to the nucleic acid to be labeled; a transferring step for transferring a transfer group contained in the reactive nucleobase derivative to the nucleotide residue containing the target nucleobase in the nucleic acid to be labeled; and a labeling step for labeling the transfer group transferred to the nucleotide residue with a radioactive material.

The present disclosure, at least in part, relates to a miRNA based logic gate that comprises an engineered RNA carrier that comprises an nuclear export signal, a target site for a first miRNA and a pre-miRNA sequence for a second miRNA. Also provided by the disclosure are recombinant viruses (e.g., recombinant adeno-associated viruses (rAAV)) for delivery of the miRNA based logic gates.