Fusion protein comprising IL13
The invention is concerned with a fusion protein comprising interleukin 13 and a regulatory cytokine, for example, an interleukin chosen from interleukin 4, interleukin 10, interleukin 27, interleukin 33, transforming growth factor beta 1, transforming growth factor beta 2, and interleukin 13, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of a condition characterized by pathological pain, chronic pain, neuro-inflammation and/or or neurodegeneration.
1. A method of treating pain, inflammation, neuropathy, or neurodegeneration in a subject in need thereof, comprising administering to the subject an effective amount of a fusion protein that comprises a first interleukin that is IL13 and a second interleukin that is IL4, IL10, or IL13.
2. The method of claim 1 , wherein the second interleukin is the IL4.
3. The method of claim 1 , wherein the second interleukin is the IL10.
4. The method of claim 1 , wherein the second interleukin is the IL13.
5. The method of claim 1 , wherein the first interleukin comprises a wild type IL13 amino acid sequence.
6. The method of claim 1 , wherein the first interleukin is a human IL13.
7. The method of claim 1 , wherein the second interleukin comprises a wild type IL4 amino acid sequence, a wild type IL10 amino acid sequence, or a wild type IL13 amino acid sequence.
8. The method of claim 1 , wherein the second interleukin is a human IL4, human IL10, or human IL13.
9. The method of claim 1 , wherein the first interleukin that is IL13 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 2 or any one of SEQ ID NOs: 9-15.
10. The method of claim 1 , wherein the first interleukin that is IL13 comprises an amino acid sequence with at least 98% sequence identity to SEQ ID NO: 2 or any one of SEQ ID NOs: 9-15.
11. The method of claim 1 , wherein the first interleukin that is IL13 comprises an amino acid sequence that is SEQ ID NO: 2 or any one of SEQ ID NOs: 9-15.
12. The method of claim 1 , wherein the second interleukin:
(a) is the IL4 and comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 1 or any one of SEQ ID NOs: 26-28,
(b) is the IL10 and comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 5, or
(c) is the IL13 and comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 2 or any one of SEQ ID NOs: 9-15.
13. The method of claim 1 , wherein the second interleukin:
(a) is the IL4 and comprises an amino acid sequence with at least 98% sequence identity to SEQ ID NO: 1 or any one of SEQ ID NOs: 26-28,
(b) is the IL10 and comprises an amino acid sequence with at least 98% sequence identity to SEQ ID NO: 5, or
(c) is the IL13 and comprises an amino acid sequence with at least 98% sequence identity to SEQ ID NO: 2 or any one of SEQ ID NOs: 9-15.
14. The method of claim 1 , wherein the second interleukin:
(a) is the IL4 and comprises an amino acid sequence that is SEQ ID NO: 1 or any one of SEQ ID NOs: 26-28,
(b) is the IL10 and comprises an amino acid sequence that is SEQ ID NO: 5, or
(c) is the IL13 and comprises an amino acid sequence that is SEQ ID NO: 2 or any one of SEQ ID NOs: 9-15.
15. The method of claim 1 , wherein the first interleukin and the second interleukin are joined by a linker.
16. The method of claim 1 , wherein a C terminus of the first interleukin is joined to an N-terminus of the second interleukin, optionally via a linker.
17. The method of claim 1 , wherein an N terminus of the first interleukin is joined to a C-terminus of the second interleukin, optionally via a linker.
18. The method of claim 1 , wherein the neuropathy is treated in the subject.
19. The method of claim 18 , wherein the neuropathy is a chemotherapy-induced neuropathy.
20. The method of claim 18 , wherein the neuropathy is a peripheral neuropathy.
21. The method of claim 18 , wherein nerve fiber degeneration is reduced in the subject.
22. The method of claim 1 , wherein the neurodegeneration is treated in the subject.
23. The method of claim 1 , wherein the pain is treated in the subject.
24. The method of claim 1 , wherein the inflammation is treated in the subject.