Recombinant virus products and methods for inhibition of expression of myotilin
The present invention relates to RNA interference-based methods for inhibiting the expression of the myotilin gene. Recombinant adeno-associated viruses of the invention deliver DNAs encoding microRNAs that knock down the expression of myotilin. The methods have application in the treatment of muscular dystrophies such as Limb Girdle Muscular Dystrophy Type 1A.
1. A recombinant adeno-associated virus encoding a myotilin (MYOT) microRNA (miRNA) comprising an antisense guide strand set out in any one of SEQ ID NOs: 5484, 7354, 7368, 7423, 7667, 7798, 7944, 7945, 8013, or 8056, wherein the recombinant adeno-associated virus lacks rep and cap genes.
2. A composition comprising the recombinant adeno-associated virus of claim 1 and a carrier, diluent, and/or adjuvant.
3. The recombinant adeno-associated virus of claim 1 , wherein the recombinant adeno-associated virus (rAAV) is rAAV-6.
4. The recombinant adeno-associated virus of claim 3 , wherein the rAAV-6 is self-complementary rAAV-6.
5. A method of inhibiting expression of the myotilin (MYOT) gene in a cell comprising contacting the cell with an effective amount of the recombinant adeno-associated virus of claim 1 .
6. A method of delivering a myotilin (MYOT) miRNA-encoding DNA to an animal in need thereof, comprising administering to the animal an effective amount of the recombinant adeno-associated virus of claim 1 .
7. A method of treating limb girdle muscular dystrophy type 1A in a subject comprising administering to the subject an effective amount of the recombinant adeno-associated virus of claim 1 .
8. The method of claim 5 , wherein the recombinant adeno-associated virus is a self-complementary rAAV-6.
9. The method of claim 6 , wherein the recombinant adeno-associated virus is a self-complementary rAAV-6.
10. The method of claim 7 , wherein the recombinant adeno-associated virus is a self-complementary rAAV-6.