Abstract: A CRISPR inhibitor molecule is provided, comprising an artificial nucleic acid construct having a first polynucleotide, the inhibitor molecule capable of establishing several points of contact with a CRISPR protein and high binding affinity thereto, is provided. The first polynucleotide may comprise a sequence selected from the group consisting of: a polynucleotide that interacts with a protospacer adjacent motif (PAM)-interaction (PI) domain of a CRISPR-associated (Cas) protein, a polynucleotide that interacts with a guide sequence of a crRNA or an equivalent position of a single-guide RNA, and a polynucleotide that interacts with a repeat region of a tracrRNA or an equivalent position of a single-guide RNA. The CRISPR inhibitor molecule may also comprise a second polynucleotide and a linker. Methods of using the CRISPR inhibitor molecule in therapeutic agent selection and creation, as well as part of a therapeutic treatment, are also provided.

Abstract: A composition, a method for selectively altering expression of a gene, and a method of selectively modulating activity of a Cas protein is provided. The composition includes a nucleotide regulator wherein the regulator is an oligonucleotide sequence at least 95% identical to a sequence selected from the group consisting of SEQ ID NOs. 1-6 and 8-19 or a functional fragment thereof and may comprise a derepressor wherein the derepressor has an oligonucleotide sequence at least 95% identical to SEQ. ID. NO. 20 or a functional fragment thereof. The method of selectively altering gene expression includes administering the composition containing a nucleotide regulator. The method of selectively modulating activity of a Cas protein includes administering a composition of a repressor and a derepressor to a subject, wherein the repressor competes with or disrupts the PM module structure of the Cas protein, and the derepressor reverses the disruption of the repressor.

Abstract: A CRISPR inhibitor molecule is provided, comprising an artificial nucleic acid construct having a first polynucleotide, the inhibitor molecule capable of establishing several points of contact with a CRISPR protein and high binding affinity thereto, is provided. The first polynucleotide may comprise a sequence selected from the group consisting of: a polynucleotide that interacts with a protospacer adjacent motif (PAM)-interaction (PI) domain of a CRISPR-associated (Cas) protein, a polynucleotide that interacts with a guide sequence of a crRNA or an equivalent position of a single-guide RNA, and a polynucleotide that interacts with a repeat region of a tracrRNA or an equivalent position of a single-guide RNA. The CRISPR inhibitor molecule may also comprise a second polynucleotide and a linker. Methods of using the CRISPR inhibitor molecule in therapeutic agent selection and creation, as well as part of a therapeutic treatment, are also provided.