Polynucleotides encoding immune modulating polypeptides
View Patent ↗The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotide molecules encoding at least one polypeptide of interest to modulate the immune response.
1. A method for increasing the activity of the immune system in a subject in need thereof comprising administering to said subject a polynucleotide comprising;
(a) a first region of linked nucleosides, said first region encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 115;
(b) a first flanking region located 5′ relative to said first region comprising a 5′ untranslated region (5′UTR) and at least one 5′ terminal cap;
(c) a second flanking region located 3′ relative to said first region comprising a 3′ untranslated region (3′UTR) and a 3′ tailing sequence of linked nucleosides;
wherein said polynucleotide comprises at least one chemically modified nucleoside, and wherein when administered to said subject, said polynucleotide expresses said polypeptide, which activates T cells and/or promotes cytokine production in the subject.
2. The method of claim 1 , wherein the administration to said subject is selected from the group consisting of prenatal administration, neonatal administration and postnatal administration.
3. The method of claim 2 , wherein the administration is parenteral.
4. The method of claim 1 , wherein the first region of linked nucleosides comprises at least an open reading frame of a nucleic acid sequence, wherein the nucleic acid sequence is SEQ ID NO: 180.
5. The method of claim 1 , wherein the 3′UTR is selected from the group consisting of SEQ ID NOs: 20-36 and the native 3′ UTR of any of the nucleic acids that encode any of SEQ ID NOs: 39, 40, 115-178, 510-519, 847-854, 963-1014, 1283-1290, 1368-1404 and 1599-1605.
6. The method of claim 1 , wherein the 3′UTR is heterologous to the 5′UTR.
7. The method of claim 1 , wherein the at least one chemically modified nucleoside is selected from the modifications of Table 12.
8. The method of claim 7 , wherein the modification is a uridine modification.
9. The method of claim 8 , wherein the uridine modification is selected from the group consisting of pseudouridine and 1-methylpseudouridine.
10. The method of claim 7 , wherein the modification is a cytidine modification.
11. The method of claim 10 , wherein the cytidine modification is 5-methylcytosine.
12. The method of claim 7 , wherein the polynucleotide comprises two chemically modified nucleosides.
13. The method of claim 12 , wherein the first chemically modified nucleoside is a uridine modification of Table 12.
14. The method of claim 13 , wherein the uridine modification is selected from the group consisting of pseudouridine and 1-methylpseudouridine.
15. The method of claim 12 , wherein the second chemically modified nucleoside is a cytidine modification of Table 12.
16. The method of claim 15 , wherein the cytidine modification is 5-methylcytosine.
17. The method of claim 12 , wherein the two chemically modified nucleosides are selected from the group consisting of pseudouridine, 1-methylpseudouridine and 5-methylcytosine.