Mg53 compositions and methods of use

Abstract

Disclosed herein are nucleic acid sequences that encode novel polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, and antibodies, which immunospecifically-bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the aforementioned polypeptide, polynucleotide, or antibody. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

1 . A composition comprising a pharmaceutically acceptable carrier or excipient, and at least one of:
 (i) an isolated and/or recombinant nucleic acid molecule having at least 90% sequence identity to at least one of SEQ ID NO. 2, 4, or 6;   (ii) an isolated and/or recombinant nucleic acid molecule that is complementary to at least a portion of the nucleic acid of (i); or   (iii) an isolated and/or recombinant nucleic acid molecule capable of hybridizing to at least a portion of the nucleic acid of (i).   
       The nucleic acid may optionally comprise a linker peptide or fusion protein component, for example, His-Tag, FLAG-Tag, fluorescent protein, GST, TAT, an antibody portion, a signal peptide, and the like, at the 5′ end, the 3′ end, or at any location within the ORF. 
     
     
         2 . The composition of  claim 1 , wherein the nucleic acid molecule further comprises, within a single open reading frame, a polynucleotide encoding a protein tag and/or a signal peptide. 
     
     
         3 . The composition of  claim 2 , wherein the protein tag is at least one of a His tag, FLAG tag, fluorescent protein, GST protein, TAT protein or combination thereof. 
     
     
         4 . The composition of  claim 2 , wherein the signal peptide results in secretion of the protein when expressed in a eukaryotic cell. 
     
     
         5 . The composition of  claim 2 , wherein the nucleic acid molecule is operably linked to a transcription regulatory nucleic acid sequence. 
     
     
         6 . The composition of  claim 5 , wherein the nucleic acid molecule and transcription regulatory nucleic acid sequence are comprised within a plasmid or vector. 
     
     
         7 . The composition of  claim 6 , wherein the plasmid is a bacterial plasmid. 
     
     
         8 . The composition of  claim 6 , wherein the vector is a eukaryotic expression vector. 
     
     
         9 . The composition of  claim 8 , wherein the vector is a viral vector. 
     
     
         10 . The composition of  claim 9 , wherein the viral vector is a retroviral vector. 
     
     
         11 . A host cell comprising the vector of  claim 6 . 
     
     
         12 . The host cell of  claim 11 , wherein the cell is a eukaryotic cell, and wherein the host cell expresses a polypeptide encoded by the nucleic acid. 
     
     
         13 . The isolated nucleic acid of  claim 1 , wherein the nucleic acid sequence encodes a polypeptide comprising an amino acid sequence of at least one of SEQ ID NO. 1, 3, or 5. 
     
     
         14 . A method for the treatment or prevention of cellular damage comprising administering a therapeutically or prophylactically effective amount of the composition of  claim 1  to an individual, wherein the composition is effective for treating or preventing cellular damage. 
     
     
         15 . The method of  claim 14 , wherein the composition is administered locally or systemically. 
     
     
         16 . The method of  claim 15 , wherein the composition is administered via intramuscular injection. 
     
     
         17 . The method of  claim 15 , wherein the composition is administered via intraperitoneal injection. 
     
     
         18 . The method of  claim 15 , wherein the composition is administered via intravenous injection. 
     
     
         19 . A method of treating or preventing muscle cell damage comprising administering a therapeutically or prophylactically effective amount of the composition of  claim 1  to an individual, wherein the composition is effective for treating or preventing muscle cell damage. 
     
     
         20 . A composition comprising a nucleic acid molecule that forms a small inhibitory RNA and that down regulates expression of a nucleic acid of at least one of SEQ ID NO. 2, 4 or 6 via RNA-interference, wherein the nucleic acid molecule is from about 10 to about 100 nucleotides in length; and wherein the inhibitory nucleic acid molecule comprises a nucleotide sequence having sufficient complementarity to an RNA transcribed from the MG53 gene for the inhibitory nucleic acid molecule to cause, directly or indirectly, cleavage of said RNA via RNA-interference.