Class of therapeutic protein based molecules
The present invention provides new compositions and methods for preventing and treating pathogen infection. In particular, the present invention provides compounds having an anchoring domain that anchors the compound to the surface of a target cell, and a therapeutic domain that can act extracellularly to prevent infection of a target cell by a pathogen, such as a virus. The present invention also comprises therapeutic compositions having sialidase activity, including protein-based compounds having sialidase catalytic domains. Compounds of the invention can be used for treating or preventing pathogen infection, and for treating and reducing allergic and inflammatory responses. The invention also provides compositions and methods for enhancing transduction of target cells by recombinant viruses. Such compositions and methods can be used in gene therapy.
1. A fusion protein, comprising:
at least one catalytic domain of a sialidase, wherein the catalytic domain of the sialidase comprises the sequence of amino acids set forth in SEQ ID NO:16 and lacks the sequence that consists of the sequence extending from amino acid 1 to amino acid 273 and from amino acid 668 to amino acid 901 of SEQ ID NO:12;
at least one peptide linker; and
at least one anchoring domain, wherein the anchoring domain is a glycosaminoglycan (GAG) binding domain of human amphiregulin comprising the amino acid sequence of SEQ ID NO:7.
2. The fusion protein of claim 1 , whose sequence comprises the sequence of amino acids set forth in SEQ ID NO:37 or SEQ ID NO:39.
3. A pharmaceutical formulation, comprising the fusion protein of claim 1 and a pharmaceutically acceptable carrier or diluent.
4. The pharmaceutical formulation of claim 3 that is formulated as a spray, an inhalant, a solution for injection, a solution for eye drops, a cream, a salve, a gel, an ointment, a pill, a tablet, a lozenge, a suspension, or a solution for oral administration.