Recombinant self-replicating polycistronic rna molecules
AssigneeNovartis AG
InventorsAnders Lilja, Peter Mason
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Abstract
This disclosure provides recombinant polycistronic nucleic acid molecules that contain at at least four nucleotide sequences that encode a protein of interest, particularly proteins that form complexes in vivo, each operably linked to a separate subgenomic promoter. In some embodiments these proteins and the complexes they form elicit potent neutralizing antibodies. Thus, presentation of herpes virus proteins using the disclosed platforms permits the generation of broad and potent immune responses useful for vaccine development.
Claims24
A self-replicating RNA molecule comprising a polynucleotide which comprises:
- a) a first nucleotide sequence encoding a first protein or fragment thereof that is operably linked to a first subgenomic promoter (SGP);
- and
- b) a second nucleotide sequence encoding a second protein or fragment thereof that is operably linked to a second SGP;
- c) a third nucleotide sequence encoding a third protein or fragment thereof that is operably linked to a third SGP;
- and
- d) a fourth nucleotide sequence encoding a fourth protein or fragment thereof that is operably linked to a fourth SGP;
- with the proviso that the first protein, the second protein, the third protein and the fourth protein are not the same protein or fragments of the same protein, the first protein is not a fragment of the second, third or fourth protein, the second protein is not a fragment of the first, third or fourth protein, the third protein is not a fragment of the first, second or fourth protein, and the fourth protein is not a fragment of the first, second or third protein;
- wherein when the self-replicating RNA molecule is introduced into a suitable cell, the first, second, third and fourth proteins or fragments thereof are produced.
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Dependencies are inferred from the claim text.