Tgf-beta receptor type ii variants and uses thereof

Abstract

In certain aspects, the present disclosure relates to polypeptides comprising a truncated, ligand-binding portion of the extracellular domain of TβRII polypeptide useful to selectively antagonize a TβRII ligand. The disclosure further provides compositions and methods for use in treating or preventing TGFβ associated disorders.

1 - 16 . (canceled) 
     
     
         17 . A method of identifying functional mutants of a TβRII polypeptide, comprising:
 a. producing a combinatorial library of genes encoding variant polypeptides; and 
 b. evaluating the ability of each variant polypeptide to bind to Transforming Growth Factor β1 and Transforming Growth Factor β3. 
 
     
     
         18 . The method of  claim 17 , wherein the library of genes is produced by enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences. 
     
     
         19 . The method of  claim 17  or  claim 18 , wherein the variant polypeptide sequences can be expressed individually. 
     
     
         20 . The method of  claim 17  or  claim 18 , wherein the variant polypeptide sequences can be expressed as a set of larger fusion proteins. 
     
     
         21 . The method of  claim 17  or  claim 18 , wherein the variant polypeptides are truncation mutants. 
     
     
         22 . The method of  claim 17  or  claim 18 , wherein the variant polypeptides are combinatorial mutants of a TβRII polypeptide. 
     
     
         23 . The method of  claim 17  or  claim 18 , wherein each gene in the library of genes includes at least a portion of a potential TβRII polypeptide sequence. 
     
     
         24 . The method of  claim 17  or  claim 18 , wherein a nucleotide sequence encoding the gene is chemically synthesized. 
     
     
         25 . The method of  claim 17 , wherein the chemically synthesized gene sequence is ligated into a vector for expression. 
     
     
         26 . The method of  claim 17  or  claim 18 , wherein the combinatorial library is produced using alanine scanning mutagenesis, linker scanning mutagenesis, saturation mutagenesis, PCR mutagenesis, or by random mutagenesis.