Oligomers

Abstract

Certain disclosed oligomers induce exon skipping during processing of myostatin pre-mRNA. The oligomers may be in a vector or encoded by the vector. The vector is used for inducing exon skipping during processing of myostatin pre-mRNA. A therapeutically effective amount of the oligomer may be administered to a subject patient such that exon skipping during processing of myostatin pre-mRNA is induced. The administration to a subject may be used in order to increase or maintain muscle mass, or slowing degeneration of muscle mass in the subject. The administration to a subject may ameliorate muscle wasting conditions, such as muscular dystrophy. Examples of such muscular dystrophies which may be so treated include Becker's muscular dystrophy, congenital muscular dystrophy, Duchenne muscular dystrophy, distal muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy (FSHD), limb-girdle muscular dystrophy, myotonic muscular dystrophy, and oculopharyngeal muscular dystrophy.

1 . (canceled) 
     
     
         2 . A method of inducing exon skipping during processing of myostatin pre-mRNA in a patient, the method comprising administering a therapeutically effective amount of a pharmaceutical composition comprising an oligomer and a pharmaceutically acceptable carrier, adjuvant, or vehicle for inducing exon skipping during processing of myostatin pre-mRNA, the oligomer comprising at least 20 contiguous bases of a base sequence selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO. 1) 
                 
                     
                   1) XCXCGACGGGXCXCAAAXAXAXCCAXAGXX; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 2) 
                 
                     
                   2) XGXACCGXCXXXCAXAGGXXXGAXGAGXCX; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 3) 
                 
                     
                   3) CCXGGGXXCAXGXCAAGXXXCAGAGAXCGG; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 4) 
                 
                     
                   4) CAGCCCAXCXXCXCCXGGXCCXGGGAAGGX; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 5) 
                 
                     
                   5) XCXXGACGGGXCXGAGAXAXAXCCACAGXX; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 17) 
                 
                     
                   6) CXGGGAAGGXXACAGCAAGA; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 18) 
                 
                     
                   7) XCXCCXGGXCCXGGGAAGGX 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         wherein X is T or U and the oligomer's sequence can vary from the above sequence at up to two base positions, and wherein the oligomer can bind to a target site in the myostatin pre-mRNA to cause exon skipping, 
         wherein the oligomer is a phosphorodiamidate morpholino oligonucleotide (PMO) or a phosphorothioate-linked 2′-O-methyl oligonucleotide (2′OMePS), 
         to the patient such that exon skipping during processing of myostatin pre-mRNA is induced. 
       
     
     
         3 . The method of  claim 2 , wherein the method is for increasing or maintaining muscle mass, or slowing degeneration of muscle mass in the patient. 
     
     
         4 . The method of  claim 2 , wherein the method is for ameliorating muscle wasting conditions. 
     
     
         5 . The method of  claim 2 , wherein the method is for ameliorating a muscular dystrophy such as Becker's muscular dystrophy, congenital muscular dystrophy, Duchenne muscular dystrophy, distal muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy (FSHD), limb-girdle muscular dystrophy, myotonic muscular dystrophy and oculopharyngeal muscular dystrophy. 
     
     
         6 . The method of  claim 2 , wherein the method is for ameliorating Duchenne muscular dystrophy.