Recombinant Virus Products and Methods for Inhibition of Expression of DUX4

• US 20140322169A1
• Filed: 07/24/2012
• Published: 10/30/2014
• Est. Priority Date: 07/25/2011
• Status: Active Grant

• Current Assignee: Research Institute at Nationwide Children's Hospital
• Original Assignee: Nationwide Children's Hospital Incorporated
• Inventors: Liu, Jian, Harper, Scott Quenton, Garwick, Sara, Wallace, Lindsay
• Granted Patent: US 9,469,851 B2
• Time in Patent Office: Days
• US Class Current: 424/93.2
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/141 MicroRNAs, miRNAs
• CPC Class Codes: C12N 2320/30 Special therapeutic applications
• CPC Class Codes: C12N 2330/51 Specially adapted vectors
• CPC Class Codes: C12N 2750/00032 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2750/14132 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2750/14143 viral genome or elements thereof as genetic vector

Abstract

The present invention relates to RNA interference-based methods for inhibiting the expression of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding microRNAs that knock down the expression of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.

Claims

1. A recombinant adeno-associated virus comprising the DUX4 miRNA-encoding DNA set out in SEQ ID NO:

1 or 2, wherein the recombinant adeno-associated virus lacks rep and cap genes.

2. A composition comprising the recombinant adeno-associated virus of claim 1.

3. A method of inhibiting expression of the DUX4 gene in a cell comprising contacting the cell with a recombinant adeno-associated virus of claim 1 or the composition of claim 2.

4. A method of delivering the DUX4 miRNA-encoding DNA to an animal in need thereof, comprising administering to the animal a recombinant adeno-associated virus comprising the DUX4 miRNA-encoding DNA set out in SEQ ID NO:

1 or the DUX4 miRNA-encoding DNA set out in SEQ ID NO;

2, wherein the recombinant adeno-associated virus lacks rep and cap genes.

5. (canceled)

6. A method of treating facioscapulohumeral muscular dystrophy comprising administering a recombinant adeno-associated virus comprising the DUX4 miRNA-encoding DNA set out in SEQ ID NO:

1 or the DUX4 miRNA-encoding DNA set out in SEQ ID NO;

2, wherein the recombinant adeno-associated virus lacks rep and cap genes.

7-10. -10. (canceled)

11. A DNA set out in SEQ ID NO:

1 encoding miDUX4.405 or set out in SEQ ID NO;

2 encoding miDUX4.1156.

12. (canceled)