Type I interferon mimetics as therapeutics for cancer, viral infections, and multiple sclerosis
The subject invention pertains to agonist peptides of type I interferons and methods of using the peptides. These peptides are based on the amino acid sequence of the C-terminus region of the type I IFN molecules and are capable of binding to the cytoplasmic domain of type I IFN receptors. Surprisingly, these peptides were found to possess the same or similar biological activity as that associated with the full-length, mature type I IFN proteins, even though these peptides do not bind to the extracellular domain of the type I IFN receptors. In one embodiment, the peptide is a peptide of IFNα. In another embodiment, the peptide is a peptide of IFNβ. Exemplified peptides of the invention include those having SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:38, SEQ ID NO:39, and SEQ ID NO:40. The subject peptides have been shown to effect increased resistance to viral infection. Peptides of the invention can be used to treat or prevent viral infections, to treat oncological disorders, and to treat autoimmune disorders, such as multiple sclerosis.
1. An agonist peptide of a type I interferon (IFN), or a polynucleotide encoding the agonist peptide; or a polynucleotide expression construct comprising the polynucleotide encoding the agonist peptide, wherein the expression construct can express the polynucleotide encoding the peptide; or a composition comprising the agonist peptide, the polynucleotide, and/or the polynucleotide expression construct; wherein the peptide does not bind to the extracellular domain of a type I IFN receptor but does bind to the cytoplasmic domain of a type I IFN receptor, and wherein the peptide consists of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:38, SEQ ID NO:39, or SEQ ID NO:40.
2. The peptide according to claim 1 , wherein the peptide comprises a protein or nucleic acid that is attached to the peptide and that targets delivery to the cell and/or that provides for translocation of the peptide across a biological membrane of the cell.
3. The peptide according to claim 1 , wherein a lipophilic group is attached to the peptide.
4. The peptide according to claim 3 , wherein the lipophilic group is a palmitoyl-lysine group.
5. The peptide according to claim 3 , wherein the peptide comprises one or more arginine amino acids at the N-terminus of the peptide, or at the C-terminus of the peptide, or both termini of the peptide.
6. The peptide according to claim 1 , wherein the peptide comprises a nuclear localization sequence (NLS) attached to the peptide.
7. The composition according to claim 1 , wherein the composition comprises a suitable carrier, diluent, or buffer.
8. The composition according to claim 1 , wherein the peptide or polynucleotide is encapsulated in a liposome.
9. The polynucleotide expression construct according to claim 1 , wherein said expression construct comprises one or more regulatory elements.
10. The peptide according to claim 1 , wherein the peptide comprises a cell-penetrating peptide (CPP) attached to the peptide.
11. The peptide according to claim 10 , wherein the CPP comprises the amino acid sequence of SEQ ID NO:43.
12. The peptide according to claim 10 , wherein the CPP comprises only arginine (R) or only lysine (K) amino acids.
13. The peptide according to claim 1 , wherein the peptide has the same or similar biological activity as that associated with a full-length type I IFN protein.
14. The peptide according to claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 1.
15. The peptide according to claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO:2.
16. The peptide according to claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO:3.
17. The peptide according to claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO:4.
18. The peptide according to claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO:38.
19. The peptide according to claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO:39.
20. The peptide according to claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO:40.