Compositions and methods for treatment of muscular dystrophy

Patent metadata

Field	Value
Publication number	US-10286085-B2
Application number	US-201414909854-A
Country	US
Kind code	B2
Filing date	Jul 26, 2014
Priority date	Aug 5, 2013
Publication date	May 14, 2019
Grant date	May 14, 2019

Abstract

The present invention features recombinant adeno-associated vectors for delivery of genes to both skeletal and cardiac muscle and methods for treatment of muscle defects, including Duchenne's muscular dystrophy.

First claim

What is claimed is:

1. A recombinant adeno-associated vector (AAV) for expression of a gene in skeletal or cardiac muscle tissue comprising a muscle-specific promoter and a gene encoding a fusion protein, wherein said fusion protein comprises:
a) a transcriptional activation element and
b) a DNA binding element, wherein said DNA binding element binds to a promoter of the utrophin gene, wherein said utrophin promoter is a mouse or human utrophin “A” promoter,
wherein said fusion protein, when expressed in said skeletal or cardiac muscle tissue, is capable of increasing utrophin expression, increasing muscle contractile force, or increasing muscle endurance, and
wherein said vector comprises the sequence of SEQ ID NO:83, 84, or 85.

2. The vector of claim 1 , wherein said muscle-specific promoter is alpha-actin.

3. The vector of claim 1 , wherein said vector further comprises at least one element selected from a group consisting of an inverted terminal repeat, a cap signal, a multicloning site, an intron splice-donor site, an intron splice-acceptor site, an epitope tag, a nuclear localization sequence, and a polyadenylation consensus sequence.

4. The vector of claim 1 , wherein said mouse or human utrophin “A” promoter comprises the sequence of SEQ ID NO:9 or SEQ ID NO:14.

5. The vector of claim 1 , wherein said human utrophin “A” promoter comprises the sequence of SEQ ID NO:10 or SEQ ID NO:12 or said mouse utrophin “A” promoter comprises the sequence of SEQ ID NO:11 or SEQ ID NO: 13.

6. The vector of claim 1 , wherein said muscle-specific promoter is constitutively expressable throughout differentiation.

7. The vector of claim 6 , wherein the muscle-specific promoter is selected from the group consisting of alpha-actin, cardiac troponin C, myosin light chain 2 A, skeletal beta-actin, CK 6, dystrophin, muscular creatine kinase, dMCK, tMCK, enh348MCK, synthetic C5-12 (Syn), Myf5, MLC1/3f. MyoD1, Myog, and Pax7.

8. The vector of claim 1 , wherein said vector has a serotype selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, and AAV9.

9. A composition comprising the vector of claim 1 and a pharmaceutically acceptable carrier.

Assignees

• Consiglio Nazionale Ricerche

Inventors

• Passananti Claudio
• Corbi Nicoletta
• Di Certo Maria Grazia
• Mattei Elisabetta
• Pisani Cinzia
• Strimpakos Georgios

Classifications

• C12N2710/16632

  Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent · CPC title

• C12N2750/14143

  viral genome or elements thereof as genetic vector · CPC title

• C07K2319/81

  containing a Zn-finger domain for DNA binding · CPC title

• C12N15/86

  Viral vectors · CPC title

• A61K48/0058 Primary

  Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct · CPC title