Peptide inhibitors of CRISPR-Cas9
Specific and broad-spectrum inhibitory peptides to CRISPR Cas9 variants (SpyCas9, SauCas9, and CjeCas9) are disclosed. A method of making and using these peptides with therapeutic CRISPR Cas9 (to improve desired targeting) or against harmful CRISPR Cas9 components (already active in a patient) is also disclosed. The peptides combined with a delivery system is also disclosed.
1. An agent selected from the group consisting of: an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 1, 3-10, and 12-28 and combinations thereof;
wherein the sequence identity is calculated over a full length of the amino acid sequence.
2. The agent of claim 1 , wherein the amino acid sequence is identical to any of SEQ ID NOs: 1, 3-10, and 12-28.
3. The agent of claim 1 , comprising a combination of two or more of the amino acid sequences having at least 90% sequence identity to any one of SEQ ID NOs: 1, 3-10, and 12-28.
4. The agent of claim 1 , wherein the agent is a peptide selected from the peptides represented by SEQ ID NOs: 6, 13, and 17 and combinations thereof.
5. A composition comprising an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 1, 3-10, and 12-28; and a pharmaceutically acceptable excipient;
wherein the sequence identity is calculated over a full length of the amino acid sequence.
6. The composition of claim 5 , wherein the composition is formulated for oral delivery.
7. The composition of claim 5 , further comprising a CRISPR Cas9 agent.
8. The composition of claim 7 , wherein the CRISPR Cas9 agent is a SpyCas9, SauCas9, or CjeCas9 variant.
9. The composition of claim 5 , wherein the amino acid sequence is a peptide selected from the peptides represented by SEQ ID NOs: 6, 13, and 17 and combinations thereof.
10. The composition of claim 5 , wherein the pharmaceutically acceptable excipient is a lipid-coated nanoparticle.
11. The agent of claim 1 , wherein the agent is an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 6.
12. The agent of claim 1 , wherein the agent is an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 13.
13. The agent of claim 1 , wherein the agent is an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 17.
14. The agent of claim 1 , wherein the agent is an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 5.
15. The agent of claim 1 , wherein the agent is an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 7.
16. The agent of claim 1 , wherein the agent is an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 16.
17. The agent of claim 1 , wherein the agent is an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 22.
18. The agent of claim 1 , wherein the agent is an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 23.