PROTEASE-RESISTANT FORMS OF VEGF-D, METHOD OF MAKING AND METHOD OF USE

摘要

The present invention provides modified VEGF-D polypeptide variants that are resistant to serine protease processing and methods of making and using the same, as well pharmaceutical compositions comprising the peptide or a polynucleotide encoding the same. The VEGF-D variants comprise a VEGF homology domain, and at least one of (1) a C-terminal propeptide that is not cleavable by a serine protease, and (2) an N-terminal propeptide that is not cleavable by a serine protease. The VEGF-D variants can be made using site- directed mutagenesis. The VEGF-D variants are useful for the treatment of diseases such as cardiovascular disease and primary and secondary lymphedema, and for the prevention of stenosis and restenosis of blood vessels.