Modified IGF1 polypeptides with increased stability and potency
A targeting fusion protein comprising a component that comprises a (i) ligand or derivative or fragment thereof that binds a pre-selected target surface protein, such as a receptor, and (ii) an active agent or therapeutic agent(s), and further optionally (iii) a multimerizing component and/or (iv) a signal sequence. In a preferred embodiment, the targeting fusion polypeptide targets muscle and is useful to treat a muscle-related disease or condition, such as muscle atrophy.
1. A modified human insulin-like growth factor-1 (IGF-1) fusion polypeptide, comprising:
a deletion of amino acids 1-3 and a deletion of amino acid 37, relative to mature human IGF-1, and a multimerizing component capable of forming a multimer with another said modified IGF-1 fusion polypeptide, wherein the multimerizing component is an Fc domain from IgG1, IgG2, IgG3, or IgG4.
2. The fusion polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO:9.
3. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 1 .
4. A composition comprising the fusion polypeptide of claim 1 and a pharmaceutically acceptable carrier.