Twisted gastrulation polypeptides and uses thereof

Abstract

In certain aspects, the present invention provides compositions and methods for altering iron metabolism to increase red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.

1 . A polypeptide comprising a Twisted Gastrulation (TWSG) polypeptide and a fragment crystallizable region (Fc) polypeptide. 
     
     
         2 . (canceled) 
     
     
         3 . The polypeptide of  claim 1 , wherein TWSG polypeptide is encodable by a polynucleotide comprising a nucleic acid sequence of SEQ ID NO: 2. 
     
     
         4 - 5 . (canceled) 
     
     
         6 . The polypeptide of  claim 1 , wherein the TWSG polypeptide comprises an amino acid sequence at least about 80% identical to the sequence of SEQ ID NO: 8. 
     
     
         7 - 15 . (canceled) 
     
     
         16 . The polypeptide of  claim 1 , wherein the Fc polypeptide comprises an amino acid sequence at least about 80% identical to the sequence of SEQ ID NO: 3, 4, 5, 6, or 7. 
     
     
         17 - 52 . (canceled) 
     
     
         53 . A multimeric polypeptide complex comprising the polypeptide of  claim 1 . 
     
     
         54 - 56 . (canceled) 
     
     
         57 . A composition comprising the polypeptide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         58 . A composition comprising the multimeric polypeptide complex of  claim 53  and a pharmaceutically acceptable carrier. 
     
     
         59 . A polynucleotide encoding the polypeptide of  claim 1 . 
     
     
         60 . (canceled) 
     
     
         61 . A composition comprising the polynucleotide of  claim 59  and a pharmaceutically acceptable carrier. 
     
     
         62 . A vector comprising at least one regulatory sequence operably linked to the polynucleotide of  claim 59 . 
     
     
         63 . A host cell expressing the vector of  claim 62 . 
     
     
         64 . A kit comprising the polypeptide of  claim 1 , and, optionally, an administration device. 
     
     
         65 . A non-human animal engineered to express, or to overexpress, the polypeptide of  claim 1 . 
     
     
         66 . A method of producing a TWSG-Fc fusion polypeptide, comprising:
 i) providing a cell comprising the polynucleotide of  claim 59 ; and   ii) culturing the cell under conditions suitable for expression of the TWSG-Fc fusion polypeptide encoded by the polynucleotide.   
     
     
         67 - 69 . (canceled) 
     
     
         70 . A method of inhibiting BMP signaling in a cell, tissue, or organ, comprising administering the polypeptide of  claim 1 . 
     
     
         71 . A method of increasing red blood cell and/or hemoglobin levels, or reducing blood transfusion-dependence (TD), in a subject, comprising administering to the subject the polypeptide of  claim 1 . 
     
     
         72 . A method of increasing iron levels in a subject, comprising administering to the subject the polypeptide of  claim 1 . 
     
     
         73 . (canceled) 
     
     
         74 . A method of treating iron overload in a subject, comprising administering to the subject the polypeptide of  claim 1 . 
     
     
         75 . (canceled) 
     
     
         76 . A method of treating dysregulation of BMP signaling in a subject, comprising administering to the subject the polypeptide of  claim 1 . 
     
     
         77 - 78 . (canceled) 
     
     
         79 . A method of treating anemia in a subject, comprising administering to the subject the polypeptide of claim  52 . 
     
     
         80 . A method of treating anemia in a subject, comprising administering to the subject a fusion protein comprising a Twisted Gastrulation (TWSG) polypeptide and a fragment crystallizable region (Fc) polypeptide. 
     
     
         81 . A method of treating anemia in a subject, comprising administering to the subject a multimeric polypeptide complex comprising a fusion protein comprising a Twisted Gastrulation (TWSG) polypeptide and a fragment crystallizable region (Fc) polypeptide. 
     
     
         82 - 100 . (canceled)