Non-coding immunomodulatory dna construct
AssigneeGilead Sciences, Inc.
InventorsMatthias SCHROFF, Christiane KLEUSS, Kerstin KAPP
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Abstract
The present invention relates to a nucleic acid molecule and its use for the modulation of the immune system. It provides a DNA construct for immunomodulation comprising at least one nucleotide in L-conformation.
Claims19
A non-coding, linear open-chained DNA construct without a phosphorothioate backbone for immunomodulation, wherein the DNA construct consists of nucleotides comprising D-DNA and at least one L-DNA nucleotide, wherein said DNA construct comprises at least one sequence motif N1N2CGN3N4 and is a TLR9 agonist, wherein:
- the N1N2 is selected from the group consisting of GT, GG, GA, AT or AA, the N3N4 is selected from the group consisting of CT or TT;
- C is deoxycytidine, G is deoxyguanosine, A is deoxyadenosine, and T is deoxythymidine;
- and
- wherein said at least one L-DNA nucleotide is located in the segment of the DNA construct consisting of five nucleotides at either the 3′-end or the 5′-end or at both the 5′- and the 3′-end of the DNA construct.
A non-coding, linear open-chained DNA construct without a phosphorothioate backbone for immunomodulation, wherein the DNA construct consists of nucleotides comprising D-DNA and at least one L-DNA nucleotide, wherein said DNA construct comprises at least three sequence motifs N1N2CGN3N4 and is a TLR9 agonist, wherein:
- N is a nucleotide selected from the group consisting of A, C, T, and G, and C is deoxycytidine, G is deoxyguanosine, A is deoxyadenosine, and T is deoxythymidine;
- a first G stretch is present at the 5′ end;
- the construct further comprises at least five nucleotides selected from the group consisting of C, T and A wherein the at least five nucleotides are located between a first and a second of said at least three sequence motifs;
- said construct further comprises a second G stretch, which is located between a second and a third of said at least three sequence motifs;
- and
- two of three 3′ terminal nucleotides are in L-conformation.
A vaccine comprising a non-coding, linear open-chained DNA construct without a phosphorothioate backbone for immunomodulation, wherein the DNA construct consists of nucleotides comprising D-DNA and at least one L-DNA nucleotide, wherein said DNA construct comprises at least one sequence motif N1N2CGN3N4, wherein N is a nucleotide selected from the group consisting of A, C, T, and G, and C is deoxycytidine, G is deoxyguanosine, A is deoxyadenosine and T is deoxythymidine, and wherein said at least one L-DNA nucleotide is located in the segment of the DNA construct consisting of five nucleotides at either the 3′-end or the 5′-end or at both the 5′- and the 3′-end of the DNA construct.
Dependencies are inferred from the claim text.