IP Library › Granted Patent US 12,410,418
Granted Patent B2
US 12,410,418 · App. 17/782,610 · Granted Sep 9, 2025

Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome

Inventors: Janel Lape (Wake Forest, NC); James Jefferson Smith (Morrisville, NC)
Assignee: Precision BioSciences, Inc.
C12N9/22A61P31/20C12N15/102C12N15/90C12N2730/10121
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Quick Facts
Patent No.
US 12,410,418
App. No.
17/782,610
Granted
Sep 9, 2025
Kind
B2
Abstract

The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced specificity and/or efficiency of indel formation, when compared to previously described HBV meganucleases. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or hepatocellular carcinoma.

Claims (14)

1. An engineered meganuclease that binds and cleaves a recognition sequence consisting of SEQ ID NO: 10 within a Hepatitis B virus genome, wherein said engineered meganuclease comprises a first subunit, a second subunit, and a linker that covalently joins said first subunit and said second subunit, wherein said first subunit binds to a first recognition half-site of said recognition sequence and comprises a first hypervariable (HVR1) region, wherein said HVR1 region comprises residues corresponding to residues 215, 217, 219, 221, 223, 224, 229, 231, 233, 235, 237, 259, 261, 262, 263, 264, 266, and 268 of SEQ ID NO: 12, and wherein said second subunit binds to a second recognition half-site of said recognition sequence and comprises a second hypervariable (HVR2) region, wherein said HVR2 region comprises residues corresponding to residues 24, 26, 28, 30, 32, 33, 38, 40, 42, 44, 46, 51, 68, 70, 75, and 77 of SEQ ID NO: 12,

wherein said first subunit has at least 97% sequence identity to residues 198-344 of SEQ ID NO: 12, and

wherein said second subunit has at least 97% sequence identity to residues 7-153 of SEQ ID NO: 12.

2. The engineered meganuclease of claim 1 , wherein said HVR1 region comprises residues 215-270 of SEQ ID NO: 12.

3. The engineered meganuclease of claim 1 , wherein said first subunit comprises a residue corresponding to residue 271 of SEQ ID NO: 12.

4. The engineered meganuclease of claim 1 , wherein said second subunit comprises a residue corresponding to residue 19 of SEQ ID NO: 12.

5. The engineered meganuclease of claim 1 , wherein said engineered meganuclease comprises the amino acid sequence of SEQ ID NO: 12.

6. The engineered meganuclease of claim 1 , wherein said HVR2 region comprises residues 24-79 of SEQ ID NO: 12.

7. The engineered meganuclease of claim 1 , wherein said HVR1 region comprises residues 215-270 of SEQ ID NO: 12, and wherein said HVR2 region comprises residues 24-79 of SEQ ID NO: 12.

8. The engineered meganuclease of claim 1 , wherein said first subunit comprises residues 198-344 of SEQ ID NO: 12.

9. The engineered meganuclease of claim 1 , wherein said second subunit comprises a residue corresponding to residue 80 of SEQ ID NO: 12.

10. The engineered meganuclease of claim 1 , wherein said second subunit comprises residues 7-153 of SEQ ID NO: 12.

11. The engineered meganuclease of claim 1 , wherein said first subunit comprises a residue corresponding to residue 271 of SEQ ID NO: 12, and wherein said second subunit comprises residues corresponding to residues 19 and 80 of SEQ ID NO: 12.

12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and said engineered meganuclease of claim 1 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 7, 2025
From: LAPE, JANEL; SMITH, JAMES JEFFERSON
To: PRECISION BIOSCIENCES, INC.
Reel/Frame 071959/0020 →
Continuity (2)
Provisional Application 62944862 · Dec 6, 2019
Related Publication 20230031465A1 · Feb 2, 2023
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