IP Library › Granted Patent US 12,419,972
Granted Patent B2
US 12,419,972 · App. 17/343,563 · Granted Sep 23, 2025

Muscle-specific nucleic acid regulatory elements and methods and use thereof

Inventors: Thierry Vandendriessche (Bierbeek, BE); Marinee Chuah (Bierbeek, BE); Pieter De Bleser (Buggenhout, BE)
Assignees: Vrije Universiteit Brussel; VIB VZW; Universiteit Gent
A61K48/0058A61K48/0075C12N15/85C12N15/86C12N15/8645C12N2710/10043C12N2750/14143C12N2800/22C12N2830/008C12N2830/15C12N2830/85
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Quick Facts
Patent No.
US 12,419,972
App. No.
17/343,563
Granted
Sep 23, 2025
Kind
B2
Abstract

The present invention relates to nucleic acid regulatory elements that are able to enhance muscle-specific expression of genes, in particular expression in cardiac muscle and/or skeletal muscle, methods employing these regulatory elements and uses of these elements. Expression cassettes and vectors containing these nucleic acid regulatory elements are also disclosed. The present invention is particularly useful for applications using gene therapy, more particularly muscle-directed gene therapy, and for vaccination purposes.

Claims (20)

1. A nucleic acid expression cassette comprising at least one nucleic acid regulatory element for enhancing muscle-specific gene expression, operably linked to a promoter and a heterologous transgene, wherein said nucleic acid regulatory element comprises the sequence set forth in SEQ ID NO:1, or a functional fragment of the sequence set forth in SEQ ID NO: 1, wherein said functional fragment consists of a nucleotide sequence selected from any one of the following: positions 143 to 233 of SEQ ID NO:1, positions 240 to 310 of SEQ ID NO: 1, or positions 90 to 233 of SEQ ID NO: 1, or comprises at least 300 contiguous nucleotides from the sequence set forth in SEQ ID NO:1.

2. The nucleic acid expression cassette according to claim 1 , wherein said nucleic acid regulatory element enhances cardiac and skeletal muscle-specific gene expression.

3. The nucleic acid expression cassette according to claim 1 , wherein said nucleic acid regulatory element has a maximal length of 600 nucleotides.

4. The nucleic acid expression cassette according to claim 1 , wherein the promoter is a muscle-specific promoter.

5. The nucleic acid expression cassette according to claim 4 , wherein the muscle-specific promoter is selected from the group consisting of: the desmin (DES) promoter, the myosin light-chain (MLC) promoter, the SPc5-12 promoter and the muscle creatine kinase (MCK) promoter.

6. The nucleic acid expression cassette according to claim 1 , wherein the transgene encodes a therapeutic protein, an immunogenic protein, or a structural protein.

7. The nucleic acid expression cassette according to claim 1 , wherein the transgene encodes a secretable therapeutic protein or a structural therapeutic protein.

8. The nucleic acid expression cassette according to claim 1 , wherein the transgene encodes a plasma factor.

9. The nucleic acid expression cassette according to claim 1 , wherein the transgene encodes dystrophin or a sarcoglycan.

10. The nucleic acid expression cassette according to claim 1 , wherein the transgene comprises the microdystrophin 1 (MD1) gene or the follistatin (FST) gene.

11. A vector comprising at least one nucleic acid regulatory element for enhancing muscle-specific gene expression, operably linked to a promoter and a transgene wherein said nucleic acid regulatory element comprises the sequence set forth in SEQ ID NO:1, or a functional fragment of the sequence set forth in SEQ ID NO: 1, wherein said functional fragment consists of a nucleotide sequence selected from any one of the following: positions 143 to 233 of SEQ ID NO:1, positions 240 to 310 of SEQ ID NO:1, or positions 90 to 233 of SEQ ID NO:1, or comprises at least 300 contiguous nucleotides from the sequence set forth in SEQ ID NO:1.

12. The vector according to claim 11 , which is a viral vector.

13. The vector according to claim 12 , wherein the viral vector is an adeno-associated viral vector.

14. A pharmaceutical composition comprising the nucleic acid expression cassette according to claim 1 , or a vector comprising the nucleic acid expression cassette, and a pharmaceutically acceptable carrier.

15. A method for muscle-directed gene therapy of Duchenne muscular dystrophy comprising administering to a subject in need thereof an effective amount of:

(i) an adeno-associated viral vector comprising the nucleic acid expression cassette according to claim 1 , wherein the transgene encodes a microdystrophin or follistatin; or

(ii) a pharmaceutical composition comprising the vector of (i) and a pharmaceutically acceptable carrier.

16. An in vitro or ex vivo method for expressing a transgene product in a muscle cell comprising:

i) introducing a nucleic acid expression cassette according to claim 1 , or a vector comprising the nucleic acid expression cassette, in a muscle cell; and

ii) expressing the transgene product in the muscle cell.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 10, 2021
From: VANDENDRIESSCHE, THIERRY; CHUAH, MARINEE; DE BLESER, PIETER
To: UNIVERSITEIT GENT; VIB VZW; VRIJE UNIVERSITEIT BRUSSEL
Reel/Frame 056502/0040 →
Priority Claims (1)
EP 14151960 · Jan 21, 2014 · regional
Continuity (2)
Continuation 15112795
Related Publication 20210395770A1 · Dec 23, 2021
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