Novel lassa virus rna molecules and compositions for vaccination
AssigneeCureVac AG
InventorsEdith JASNY, Benjamin PETSCH, Hans Wolfgang GROSSE
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Abstract
The present invention is directed to RNA suitable for use in treatment and/or prophylaxis of an infection with Lassa virus (LASV) or of a disorder related to such an infection. The invention further concerns a method of treating or preventing a disorder or a disease, first and second medical uses of the RNA, compositions, and vaccines. Further, the invention is directed to a kit, particularly to a kit of parts, comprising the RNA, compositions and vaccines.
Claims49
RNA comprising at least one coding sequence encoding at least one antigenic peptide or protein derived from a Lassa virus (LASV) protein or a fragment or variant thereof, wherein said coding sequence is operably linked to a 5′-UTR derived from a HSD17B4 gene, a NDUFA4 gene, or a RPL32 gene and/or a 3′-UTR derived from a PSMB3 gene, a CASP1 gene, an ALB7 gene, or an alpha-globin gene.
RNA according to any one of the preceding claims, wherein the LASV protein is derived from glycoprotein precursor (GPC), a prefusion-stabilized GPC, nucleoprotein (NP), zinc-binding matrix protein (Z), or a variant, fragment, or combination thereof, wherein GPC, prefusion-stabilized GPC, NP, Z are preferably full-length proteins.
RNA according to any one of the preceding claims, wherein
- said at least one coding sequence encodes at least one antigenic peptide or protein derived from LASV GPC comprising or consisting of an amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 1-254 or a fragment or a variant thereof;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut1” or “GPCstabilized”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 3567-3820 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut2”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 22949-22980 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut3”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 24645-24676 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut4”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 26341-26372 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut5”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 28037-28068 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut6”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 29733-29764 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut7”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 31429-31460 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut8”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 33125-33156 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut9”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 34821-34852 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut10”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 36517-36548 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut11”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 38213-38244 or a fragment or variant of any of these sequences,
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV prefusion-stabilized GPC (“GPCmut12”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 39909-39940 or a fragment or variant of any of these sequences,
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from LASV GPC lacking the cytoplasmic tail (“GPCmut13”) comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 41605- 41636 or a fragment or variant of any of these sequences,
- said at least one coding sequence encodes at least one antigenic peptide or protein derived from LASV NP comprising or consisting of an amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 7547-7797 or a fragment or a variant thereof;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from HsPLAT_NP comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 17968-18001 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from HsALB_NP comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 19328-19361 or a fragment or variant of any of these sequences;
- said at least one coding sequence encoding at least one antigenic peptide or protein derived from IgE_NP comprising or consisting of at least one amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 20689-20722 or a fragment or variant of any of these sequences;
- said at least one coding sequence encodes at least one antigenic peptide or protein derived from LASV Z comprising or consisting of an amino acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO:
- 11166-11347 or a fragment or a variant thereof.
RNA according to any one of the preceding claims, wherein
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 255-2286 or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 3821-6106 (encoding GPCmut1) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 22981-23108 (encoding GPCmut2) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 24677-24804 (encoding GPCmut3) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 26373-26500 (encoding GPCmut4) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 28069-28196 (encoding GPCmut5) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 29765-29892 (encoding GPCmut6) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 31461-31588 (encoding GPCmut7) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 33157-33284 (encoding GPCmut8) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 34853-34980 (encoding GPCmut9) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 36549-36676 (encoding GPCmut10) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 38245-38372 (encoding GPCmut11) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 39941-40068 (encoding GPCmut12) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 41637-41764 (encoding GPCmut13) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 7798-9805 (encoding NP) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 18002-18103 (encoding SP- HsPLAT_NP) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 19362-19463 (encoding SP- HsALB_NP) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 20723-20824 (encoding SP- IgE_NP) or a fragment or a fragment or variant of any of these sequences;
- said the at least one coding sequence comprises or consists of at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs:
- 11348-12803 (encoding Z) or a fragment or a fragment or variant of any of these sequences.
RNA according to any one of the preceding claims, wherein the at least one coding sequence is a codon modified coding sequence, wherein the amino acid sequence encoded by the at least one codon modified coding sequence is preferably not being modified compared to the amino acid sequence encoded by the corresponding wild type coding sequence.
RNA according to any one of the preceding claims, wherein the RNA comprises a 5′-cap structure, preferably m7G(5′), m7G(5′)ppp(5′)(2′OMeA), or m7G(5′)ppp(5′)(2′OMeG), wherein cap1 (m7G(5′)ppp(5′)(2′OMeA), or m7G(5′)ppp(5′)(2′OMeG) is particularly preferred.
RNA according to any one of the preceding claims, wherein the RNA comprises at least one poly(A) sequence, preferably comprising 30 to 200 adenosine nucleotides, preferably about 64 adenosine nucleotides (A64), about 100 adenosine nucleotides (A100) or about 150 adenosine nucleotides.
RNA according to any one of the preceding claims, wherein the RNA comprises at least one histone stem-loop, wherein the histone stem-loop preferably comprises a nucleic acid sequence according to SEQ ID NOs:
- 13842 or 13843 or a fragment or variant thereof.
RNA according to any one of the preceding claims wherein
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 2287-3566, 14056-15207 (encoding GPC) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 6107-7546, 15208-16743 (encoding GPCmut1) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 23109-24644 (encoding GPCmut2) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 24805-26340 (encoding GPCmut3) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 26501-28036 (encoding GPCmut4) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 28197-29732 (encoding GPCmut5) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 29893-31428 (encoding GPCmut6) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 31589-33124 (encoding GPCmut7) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 33285-34820 (encoding GPCmut8) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 34981-36516 (encoding GPCmut9) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 36677-38212 (encoding GPCmut10) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 38373-39908 (encoding GPCmut11) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 40069-41604 (encoding GPCmut12) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 41765-43300 (encoding GPCmut13) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 9806-11165, 16744-17967 (encoding NP) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 18104-19327, 19464- 20687, 20825-22048 (encoding SP-NP) or a fragment or variant of any of these sequences;
- said RNA comprises or consists of an RNA sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 12804-13803, 22049-22948 (encoding Z) or a fragment or variant of any of these sequences.
Kit or kit of parts according to claim 45 or 46 further comprising Ringer lactate solution.
Dependencies are inferred from the claim text.