RNA encoding an antibody
The present invention relates to a RNA encoding an antibody or a fragment or variant thereof and a composition, in particular a passive vaccine, comprising such an RNA. The present invention further relates to the use of such an RNA or of such a composition for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention also relates to a combination of at least two modified RNA's, in particular wherein one RNA encodes a heavy chain variable region of an antibody and another RNA encodes the corresponding light chain variable region of said antibody.
1. A composition comprising:
(I) an RNA comprising
(a) at least a first coding sequence, wherein the first coding sequence comprises a nucleic acid sequence at least 90% identical to the RNA sequence of SEQ ID NO: 61574 and encoding a polypeptide according to SEQ ID NO: 61573; and
(b) at least a second coding sequence, wherein the second coding sequence comprises a nucleic acid sequence at least 90% identical to the RNA sequence of SEQ ID NO: 61585 and encoding a polypeptide according to SEQ ID NO: 61584, wherein the first coding sequence and the second coding sequence are present in the same RNA molecule; or
(II)
(a) at least a first RNA molecule comprising at least a first coding sequence, wherein the first coding sequence comprises a nucleic acid sequence at least 90% identical to the RNA sequence of SEQ ID NO: 61574 and encoding a polypeptide according to SEQ ID NO: 61573; and
(b) at least a second RNA molecule comprising at least a second coding sequence, wherein the second coding sequence comprises a nucleic acid sequence at least 90% identical to the RNA sequence of SEQ ID NO: 61585 and encoding a polypeptide according to SEQ ID NO: 61584.
2. The composition according to claim 1 , comprising:
(I) an RNA comprising
(a) at least a first coding sequence, wherein the first coding sequence comprises a nucleic acid sequence at least 90% identical to the RNA sequence of SEQ ID NO: 61574 and encoding a polypeptide according to SEQ ID NO: 61573; and
(b) at least a second coding sequence, wherein the second coding sequence comprises a nucleic acid sequence at least 90% identical to the RNA sequence of SEQ ID NO: 61585 and encoding a polypeptide according to SEQ ID NO: 61584, wherein the first coding sequence and the second coding sequence are present in the same RNA molecule.
3. The composition according to claim 1 , comprising:
(II)
(a) at least a first RNA molecule comprising at least a first coding sequence, wherein the first coding sequence comprises a nucleic acid sequence at least 90% identical to the RNA sequence of SEQ ID NO: 61574 and encoding a polypeptide according to SEQ ID NO: 61573; and
(b) at least a second RNA molecule comprising at least a second coding sequence, wherein the second coding sequence comprises a nucleic acid sequence at least 90% identical to the RNA sequence of SEQ ID NO: 61585 and encoding a polypeptide according to SEQ ID NO: 61584.
4. The composition according to claim 3 , wherein the first and/or the second RNA is monocistronic.
5. The composition according to claim 3 , wherein the first and the second RNA is mRNA.
6. The composition according to claim 5 , wherein
the G/C content of the first and second coding sequences of the RNAs is increased compared to the G/C content of the corresponding coding sequence of the corresponding wild-type RNA, and/or wherein
the C content of the first and second coding sequences of the RNAs is increased compared to the C content of the corresponding coding sequence of the corresponding wild-type RNA, and/or wherein
the codons in the first and second coding sequences of the RNA are adapted to human codon usage.
7. The composition according to claim 5 , wherein the first and the second RNA comprise a 5′-CAP structure and at least one 3′-untranslated region element (3′-UTR element).
8. The composition according to claim 5 , wherein the first and/or the second RNA comprises at least one histone stem-loop.
9. A method of treating cancer, wherein the method comprises administering to a subject in need thereof an effective amount of the composition according to claim 1 .
10. The method according to claim 9 , further defined as a method of treating a metastatic cancer.
11. The composition according to claim 3 , comprising:
(II)
(a) at least a first RNA molecule comprising at least a first coding sequence, wherein the first coding sequence comprises a nucleic acid sequence at least 95% identical to the RNA sequence of SEQ ID NO: 61574 and encoding a polypeptide according to SEQ ID NO: 61573; and
(b) at least a second RNA molecule comprising at least a second coding sequence, wherein the second coding sequence comprises a nucleic acid sequence at least 95% identical to the RNA sequence of SEQ ID NO: 61585 and encoding a polypeptide according to SEQ ID NO: 61584.
12. The composition according to claim 7 , wherein the first and the second mRNAs comprise a modified nucleoside.
13. The composition according to claim 12 , wherein the modified nucleoside is N1-methyl-pseudouridine.
14. The composition according to claim 2 , wherein the RNA is a mRNA.
15. The composition according to claim 14 , comprising:
(I) an RNA comprising
(a) at least a first coding sequence, wherein the first coding sequence comprises a nucleic acid sequence at least 95% identical to the RNA sequence of SEQ ID NO: 61574 and encoding a polypeptide according to SEQ ID NO: 61573; and
(b) at least a second coding sequence, wherein the second coding sequence comprises a nucleic acid sequence at least 95% identical to the RNA sequence of SEQ ID NO: 61585 and encoding a polypeptide according to SEQ ID NO: 61584.
16. The composition according to claim 14 , wherein said first and said second coding sequences are separated by an internal ribosome entry site (IRES).
17. The composition according to claim 14 , wherein the mRNA comprises a 5′-CAP structure and at least one 3′-untranslated region element (3′-UTR element).
18. The composition according to claim 17 , wherein the mRNA comprises a modified nucleoside.
19. The composition according to claim 18 , wherein the modified nucleoside is N1-methyl-pseudouridine.