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. An isolated polypeptide comprising an amino acid sequence that begins at any of the amino acids from amino acid 270 to amino acid 290 of the Actinomyces viscosus sialidase protein sequence (SEQ ID NO:12) and ends at any of the amino acids from amino acid 665 to amino acid 901 of the Actinomyces viscosus sialidase protein sequence (SEQ ID NO:12), wherein the isolated polypeptide does not comprise the sequence extending from amino acid 1 to amino acid 269 of SEQ ID NO:12 and wherein the isolated polypeptide has sialidase activity.
2. The isolated polypeptide of claim 1 , comprising an amino acid sequence that begins at any of the amino acids from amino acid amino acids 270 to 290 of the Actinomyces viscosus sialidase protein sequence (SEQ ID NO:12) and ends at any of amino acid residues 665 to 681 of the Actinomyces viscosus sialidase protein sequence (SEQ ID NO:12).
3. The isolated polypeptide of claim 2 , comprising the amino acid sequence of SEQ ID NO:16.
4. The isolated polypeptide of claim 2 , comprising an amino acid sequence that begins at amino acid 274 the Actinomyces viscosus sialidase protein sequence (SEQ ID NO:12) and ends at amino acid 681 of the Actinomyces viscosus sialidase protein sequence (SEQ ID NO:12).
5. The isolated polypeptide of claim 2 , comprising an amino acid sequence that begins at amino acid 290 of the Actinomyces viscosus sialidase protein sequence SEQ ID NO:12) and ends at amino acid 666 of the Actinomyces viscosus sialidase protein sequence (SEQ ID NO:12).
6. The isolated polypeptide of claim 2 , comprising an amino acid sequence that begins at amino acid 290 the Actinomyces viscosus sialidase protein sequence (SEQ ID NO:12) and ends at amino acid 681 of the Actinomyces viscosus sialidase protein sequence (SEQ ID NO: 12).
7. A pharmaceutical formulation comprising the isolated polypeptide of claim 1 .
8. A pharmaceutical formulation comprising the isolated polypeptide of claim 2 .
9. A method of treating or preventing viral infection by influenza, comprising: applying a therapeutically effective amount of the formulation of claim 7 to epithelial cells of a subject.
10. A method of treating or preventing viral infection by influenza, comprising: applying a therapeutically effective amount of the formulation of claim 8 to epithelial cells of a subject.
11. The isolated polypeptide of claim 1 , comprising an amino acid sequence that begins at amino acid 274 of the Actinomyces viscosus sialidase protein sequence (SEQ ID NO:12) and ends at amino acid 666 of the Actinomyces viscosus sialidase protein sequence (SEQ ID NO:12), wherein the isolated polypeptide does not comprise the sequence that extends from amino acid 1 to amino acid 269 of SEQ ID NO:12 and does not comprise the sequence that extends from amino acid 667 to amino acid 901 of SEQ ID NO:12.
12. A pharmaceutical formulation comprising the isolated polypeptide of claim 11 .
13. A method of treating or preventing viral infection by influenza, comprising: applying a therapeutically effective amount of the formulation of claim 12 to epithelial cells of a subject.
14. The method of claim 9 , wherein the method comprises inhaling the formulation.
15. The method of claim 10 , wherein the method comprises inhaling the formulation.
16. A method of treating or preventing viral infection by parainfluenza, comprising: applying a therapeutically effective amount of the formulation of claim 7 to epithelial cells of a subject.
17. The method of claim 16 , wherein the method comprises inhaling the formulation.
18. A method of treating or preventing viral infection by parainfluenza, comprising: applying a therapeutically effective amount of the formulation of claim 8 to epithelial cells of a subject.
19. A method of treating or preventing viral infection by
parainfluenza, comprising: applying a therapeutically effective amount of the formulation of claim 12 to epithelial cells of a subject.
20. The method of claim 19 , wherein the method comprises inhaling the formulation.
21. The method of claim 20 , wherein the method comprises inhaling the formulation.