Granted Patent B2

US 12,083,188 · App. 16/886,129 · Granted Sep 10, 2024

Inventors: Stephanie Tagliatela (San Francisco, CA); Anne Tanenhaus (Brisbane, CA); Kartik Ramamoorthi (San Francisco, CA); Andrew Young (Redwood City, CA); David Oberkofler (San Francisco, CA)

Assignee: Encoded Therapeutics, Inc.

A61K48/0058C07K14/4705C07K14/705C12N7/00C12N15/86C07K2319/71C12N2750/14143C12N2800/30C12N2830/008

Abstract

Claims (20)

1. A composition comprising a polynucleotide, wherein the polynucleotide comprises a nucleic acid sequence encoding a non-naturally occurring DNA binding protein comprising a DNA binding domain, wherein the DNA binding domain is a zinc finger DNA binding domain comprising SEQ ID NO: 414.

2. The composition of claim 1 , wherein the DNA binding domain binds a target site comprising SEQ ID NO: 38.

3. The composition of claim 1 , wherein the DNA binding domain comprises an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of: SEQ ID NO: 26, SEQ ID NO: 93, and SEQ ID NO: 168.

4. The composition of claim 1 , wherein the DNA binding domain comprises an amino acid sequence having at least 90% sequence identity to a sequence selected from the group consisting of: SEQ ID NO: 26, SEQ ID NO: 93, and SEQ ID NO: 168.

5. The composition of claim 1 , wherein the DNA binding domain comprises a sequence selected from the group consisting of: SEQ ID NO: 26, SEQ ID NO: 93, and SEQ ID NO: 168.

6. The composition of claim 1 , wherein the non-naturally occurring DNA binding protein further comprises a transcription activating domain (TAD), a nuclear localization sequence (NLS), or both.

7. The composition of claim 6 , wherein the non-naturally occurring DNA binding protein further comprises the TAD and the NLS, and wherein the non-naturally occurring DNA binding protein is capable of upregulating endogenous progranulin (PGRN) expression in a cell.

8. The composition of claim 7 , wherein the TAD is selected from the group consisting of: (i) VPR (SEQ ID NO: 114), VP64 (SEQ ID NO: 95), CITED2 (SEQ ID NO: 98), or CITED4 (SEQ ID NO: 97), (ii) a sequence having at least 80% sequence identity to SEQ ID NO: 114, 95, 98 or 97, or (iii) any combination of any one of (i) and (ii).

9. The composition of claim 7 , wherein the DNA binding domain comprises an amino acid sequence having at least 90% sequence identity to a sequence selected from the group consisting of: SEQ ID NO: 26, SEQ ID NO: 93, and SEQ ID NO: 168.

10. The composition of claim 9 , wherein the non-naturally occurring DNA binding protein comprises an amino acid sequence having at least 90% sequence identity to a sequence selected from the group consisting of: SEQ ID NO: 10, SEQ ID NO: 59, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 345, SEQ ID NO: 346, SEQ ID NO: 16, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 347, SEQ ID NO: 348, SEQ ID NO: 349, SEQ ID NO: 350, SEQ ID NO: 340, SEQ ID NO: 342, and SEQ ID NO: 343.

11. The composition of claim 10 , wherein the non-naturally occurring DNA binding protein comprises the amino acid sequence selected from the group consisting of: SEQ ID NO: 10, SEQ ID NO: 59, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 345, SEQ ID NO: 346, SEQ ID NO: 16, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 347, SEQ ID NO: 348, SEQ ID NO: 349, SEQ ID NO: 350, SEQ ID NO: 340, SEQ ID NO: 342, and SEQ ID NO: 343.

12. The composition of claim 6 , wherein the nucleic acid sequence encoding the non-naturally occurring DNA binding protein is part of an expression cassette, and wherein the expression cassette comprises a regulatory element operably linked to the nucleic acid sequence encoding the non-naturally occurring DNA binding protein.

13. The composition of claim 12 , wherein the regulatory element is selected from the group consisting of: an intron, an enhancer, a promoter, a UTR, a stability element, a WPRE sequence, a Kozak consensus sequence, a posttranslational response element, a microRNA binding site, a polyadenylation (polyA) sequence, and any combination thereof.

14. The composition of claim 13 , wherein the regulatory element comprises a nucleic acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of: SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 182, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 326, or SEQ ID NO: 327 and any combination thereof.

15. The composition of claim 13 , wherein the regulatory element comprises a nucleic acid sequence having at least 90% sequence identity to a sequence selected from the group consisting of: SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 182, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 326, or SEQ ID NO: 327, and any combination thereof.

16. The composition of claim 13 , wherein the regulatory element is selected from the group consisting of: SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 182, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 326, or SEQ ID NO: 327, and any combination thereof.

17. The composition of claim 12 , wherein the expression cassette is incorporated into an expression vector.

18. The composition of claim 17 , wherein the expression vector is an adeno-associated virus (AAV) vector.

19. The composition of claim 18 , wherein the AAV vector is selected from the group consisting of: AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, rh10, avian AAV, bovine AAV, canine AAV, equine AAV, primate AAV, non-primate AAV, ovine AAV, scAAV, scAAV1, scAAV2, scAAV5, scAAV8, scAAV9, and hybrids thereof.

20. The composition of claim 18 , wherein the composition is a pharmaceutical composition comprising the AAV vector and one or more pharmaceutically acceptable excipients.

Assignments (1)

Continuity (9)

Cited By (1)

US 12,692,516