Artificial nucleic acid molecules encoding a norovirus antigen and uses thereof
The present invention is directed to an artificial nucleic acid and to polypeptides suitable for use in treatment or prophylaxis of an infection with Norovirus or a disorder related to such an infection. In particular, the present invention concerns a Norovirus vaccine. The present invention is directed to an artificial nucleic acid, polypeptides, compositions and vaccines comprising the artificial nucleic acid or the polypeptides. The invention further concerns a method of treating or preventing a disorder or a disease, first and second medical uses of the artificial nucleic acid, polypeptides, compositions and vaccines. Further, the invention is directed to a kit, particularly to a kit of parts, comprising the artificial nucleic acid, polypeptides, compositions and vaccines.
1. Artificial nucleic acid molecule comprising at least one coding region encoding a Norovirus VP1 polypeptide, said coding region having at least 90% identity to a sequence of SEQ ID NOs: 39713-39746, wherein the artificial nucleic acid molecule comprises at least one heterologous 5′ and/or 3′ untranslated region (UTR).
2. The artificial nucleic acid molecule of claim 1 , wherein the artificial nucleic acid is monocistronic, bicistronic or multicistronic.
3. The artificial nucleic acid molecule of claim 1 , wherein the artificial nucleic acid is an mRNA.
4. The artificial nucleic acid molecule of claim 3 , wherein the artificial nucleic acid comprises a 5′-cap structure.
5. The artificial nucleic acid molecule of claim 1 , wherein the G/C content of the coding region of the mRNA sequence is increased compared to the G/C content of the corresponding coding sequence of the wild type mRNA, or wherein the C content of the coding region of the mRNA sequence is increased compared to the C content of the corresponding coding sequence of the wild type mRNA, or wherein the codon usage in the coding region of the mRNA sequence is adapted to the human codon usage, or wherein the codon adaptation index (CAI) is increased or maximised in the coding region of the mRNA sequence, wherein the encoded amino acid sequence of the mRNA sequence is preferably not being modified compared to the encoded amino acid sequence of the wild type mRNA.
6. The artificial nucleic acid molecule of claim 1 , wherein the artificial nucleic acid comprises at least one histone stem-loop.
7. The artificial nucleic acid molecule of claim 1 , wherein the 3′-UTR comprises at least one heterologous 3′-UTR element.
8. The artificial nucleic acid molecule of claim 1 , wherein the 3′-UTR comprises a poly(A) sequence and/or a poly(C) sequence.
9. The artificial nucleic acid molecule of claim 1 , wherein the 5′-UTR comprises at least one heterologous 5′-UTR element.
10. The artificial nucleic acid molecule of claim 1 , comprising the following elements:
a) optionally a 5′-cap structure,
b) the at least one coding region,
c) a poly(A) tail comprising 10 to 200 adenosine nucleotides,
d) optionally a poly(C) tail comprising 10 to 200 cytosine nucleotides, and
e) optionally a histone stem-loop.
11. The artificial nucleic acid molecule of claim 10 , comprising
a 3′-UTR element comprising a nucleic acid sequence, which is derived from an α-globin gene.
12. The artificial nucleic acid molecule of claim 1 said coding region having at least 95% identity to a sequence of SEQ ID NOs: 39713-39746.
13. The artificial nucleic acid molecule of claim 10 , comprising
a 5′-UTR element, which comprises or consists of a nucleic acid sequence, which is derived from the 5′-UTR of a TOP gene.
14. The artificial nucleic acid molecule of claim 1 , wherein the coding region comprises a chemically modified nucleotide.
15. A method of treating or preventing a Norovirus infection, wherein the method comprises administering to a subject in need thereof the artificial nucleic acid according to claim 1 .
16. The artificial nucleic acid molecule of claim 1 , said coding region having at least 90% identity to a sequence of SEQ ID NOs: 39743.