Methods and compositions for modulating sialic acid production and treating hereditary inclusion body myopathy

Abstract

According to certain embodiments of the present invention, methods for modulating the production of sialic acid in a system are provided, which comprise providing the system with a wild-type GNE-encoding nucleic acid sequence. According to such embodiments, the system may comprise a cell, muscular tissue, or other desirable targets. Similarly, the present invention encompasses methods for producing wild-type GNE in a system that comprises a mutated endogenous GNE-encoding sequence. In other words, the present invention includes providing, for example, a cell or muscular tissue that harbors a mutated (defective) GNE-encoding sequence with a functional wild-type GNE encoding sequence.

What is claimed is: 
     
         1 . A method for modulating the production of sialic acid in a system, which comprises providing the system with a wild-type GNE-encoding nucleic acid sequence. 
     
     
         2 . The method of  claim 1 , wherein the wild-type GNE-encoding nucleic acid sequence comprises a promoter operably connected to the wild-type GNE-encoding nucleic acid sequence. 
     
     
         3 . The method of  claim 2 , wherein the promoter is the CMV promoter. 
     
     
         4 . The method of  claim 2 , wherein the wild-type GNE-encoding nucleic acid sequence is injected into the system, wherein the system comprises muscle tissue of a mammal. 
     
     
         5 . The method of  claim 2 , wherein the wild-type GNE-encoding nucleic acid sequence is disposed within or is connected to a lipid nanoparticle. 
     
     
         6 . The method of  claim 5 , wherein the wild-type GNE-encoding nucleic acid sequence consists of SEQ ID NO: 9. 
     
     
         7 . The method of  claim 5 , wherein the lipid nanoparticle comprises one or more agents capable of recognizing and binding to a muscle cell or a component thereof. 
     
     
         8 . A method for producing wild-type GNE in a system, wherein the system comprises a mutated endogenous GNE-encoding sequence, which comprises providing the system with a wild-type GNE-encoding nucleic acid sequence. 
     
     
         9 . The method of  claim 8 , wherein the wild-type GNE-encoding nucleic acid sequence comprises a promoter operably connected to the wild-type GNE-encoding nucleic acid sequence. 
     
     
         10 . The method of  claim 9 , wherein the promoter is the CMV promoter. 
     
     
         11 . The method of  claim 9 , wherein the wild-type GNE-encoding nucleic acid sequence is injected into the system, wherein the system comprises muscle tissue of a mammal. 
     
     
         12 . The method of  claim 9 , wherein the wild-type GNE-encoding nucleic acid sequence is disposed within or is connected to a lipid nanoparticle. 
     
     
         13 . The method of  claim 12 , wherein the wild-type GNE-encoding nucleic acid sequence consists of SEQ ID NO: 9. 
     
     
         14 . The method of  claim 12 , wherein the lipid nanoparticle comprises one or more agents capable of recognizing and binding to a muscle cell or a component thereof. 
     
     
         15 . A method for treating, preventing, or ameliorating the effects of Hereditary Inclusion Body Myopathy, which comprises providing a patient with a wild-type GNE-encoding nucleic acid sequence. 
     
     
         16 . The method of  claim 15 , wherein the wild-type GNE-encoding nucleic acid sequence comprises a promoter operably connected to the wild-type GNE-encoding nucleic acid sequence. 
     
     
         17 . The method of  claim 16 , wherein the promoter is the CMV promoter. 
     
     
         18 . The method of  claim 16 , wherein the wild-type GNE-encoding nucleic acid sequence is injected into muscle tissue of the patient. 
     
     
         19 . The method of  claim 16 , wherein the wild-type GNE-encoding nucleic acid sequence is disposed within or is connected to a lipid nanoparticle. 
     
     
         20 . The method of  claim 19 , wherein the wild-type GNE-encoding nucleic acid sequence consists of SEQ ID NO: 9. 
     
     
         21 . The method of  claim 19 , wherein the lipid nanoparticle comprises one or more agents capable of recognizing and binding to a muscle cell or a component thereof. 
     
     
         22 . The method of  claim 21 , wherein the lipid nanoparticle is administered to the patient intravenously. 
     
     
         23 . A composition for expressing wild-type GNE in a system, which comprises a wild-type GNE-encoding nucleic acid sequence disposed within or connected to a lipid nanoparticle. 
     
     
         24 . The composition of  claim 22 , wherein the lipid nanoparticle comprises one or more agents capable of recognizing and binding to a muscle cell or a component thereof. 
     
     
         25 . The composition of  claim 22 , wherein the wild-type GNE-encoding nucleic acid sequence consists of SEQ ID NO: 9.