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US 12,442,005 B2Granted
Artificial nucleic acid molecules for improved protein expression
AssigneeCureVac AG
InventorsAndreas Thess, Thomas Schlake, Stefanie Grund
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Abstract
The invention relates to a method for stimulating an immune response by intramuscular injection of an artificial nucleic acid molecule comprising an open reading frame encoding an antigen and a 3′-UTR comprising at least two poly(A) sequences. The method may yield an increased immune response to the antigen or an increased neutralizing antibody response to the antigen.
Claims41
A method for stimulating an immune response in an organism, the method comprising administering to the organism, by intramuscular injection, a RNA molecule comprising:
- a) a 5′-cap structure;
- b) at least one open reading frame (ORF) encoding an antigen;
- and
- c) a heterologous 3′-untranslated region (3′-UTR) comprising at least a first and a second poly(A) sequence, wherein:
- (i) the first poly(A) sequence comprises at least 20 adenine nucleotides;
- and
- (ii) the second poly(A) sequence comprises at least 60 adenine nucleotides,
- wherein the first and the second poly(A) sequences are separated by a linker nucleic acid sequence comprising at least 3 consecutive nucleotides that are not adenine nucleotides,
- wherein when the RNA molecule is administered intramuscularly to the organism, the RNA molecule yields increased expression of the antigen encoded by the at least one open reading frame in comparison to the expression from a reference nucleic acid molecule comprising an identical nucleic acid sequence as the RNA molecule but lacking the linker nucleic acid sequence.
6 more elements
Dependencies are inferred from the claim text.