Aptamer construct
AssigneeDeakin University
InventorWei Duan
Life of this patent
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Abstract
The present disclosure relates to aptamers and uses thereof, in particular, aptamers which specifically bind to CD133 and which are particularly useful in the diagnosis and/or treatment of cancer.
Claims34
An aptamer comprising the sequence 5′-X-ACGUAUACUAU-Y-3′ (SEQ ID NO:1), wherein the sequence of X and Y are complementary so as to be capable of base pairing and wherein X and Y individually comprise a length of CG paired nucleotides sufficient to permit attachment of at least one moiety thereto.
The aptamer according to any preceding claim wherein the CG paired nucleotides comprise the stem region of the aptamer.
The aptamer according to any preceding claim which is a hybrid RNA/DNA aptamer.
The aptamer according to any preceding claim which exhibits a dissociation constant (KD) for CD133 of about 24 nM or less.
The aptamer according to any preceding claim which specifically binds to CD133.
The aptamer according to any preceding claim comprising the sequence 5′-CGCGCGCCGCACGUAUACUAUGCGGCGCGCG-3′ (SEQ ID NO:2).
The aptamer according to any preceding claim wherein the moiety is a DNA stain or molecule used in chemotherapeutic treatment.
The aptamer according to any preceding claim wherein attachment of the moiety is by intercalation.
The aptamer according to any preceding claim comprising one or more modifications that increase aptamer stability.
The aptamer according to any preceding claim wherein the pyrimidine nucleotide bases (C and/or U) in the loop region are 2′-fluoro (2′-F) modified.
The aptamer according to any preceding claim wherein the 3′ end is coupled to a phosphate group, a phosphate ester, or an inverted dT ((invdT-3′).
The aptamer according to any preceding claim wherein the 5′ end is coupled to a dye.
The aptamer according to any preceding claim comprising the sequence 5′-X-A(2′fC)G(2′-fU)A(2′fU)A(2′fC)(2′fU)A(2′fU)-Y-(inv dT)-3′ (SEQ ID NO:4) wherein X and Y are complementary so as to be capable of base pairing and wherein X and Y individually comprise a length of CG paired nucleotides wherein C is 5-methyl dC, f=2-fluoro and inv dT=an inverted dT and wherein the length of X and Y is sufficient to permit the attachment of at least one moiety thereto.
The aptamer according to any preceding claim comprising the sequence 5′-mCGmCGmCGmCmCGmCA(2′fC)G(2′-fU)A(2′fU)A(2′fC)(2′fU)A(2′fU)GmCGGmCGmCGmCG-(inv dT)-3′ (SEQ ID NO:5), wherein C=5-methyl dC, f=2-fluoro and inv dT=an inverted dT.
An aptamer having substantially the same ability to bind to CD133 as that of an aptamer comprising the sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4 or SEQ ID NO:5.
An aptamer comprising a sequence having at least 95% identity to any one of SEQ ID NO:2, SEQ ID NO:4 or SEQ ID NO:5.
An aptamer according to any preceding claim which specifically binds to CD133+ cells(s).
The aptamer according to claim 24, wherein the CD133+ cell(s) are cancer stem cell(s).
A diagnostic or theranostic agent comprising an aptamer according to any preceding claim.
Dependencies are inferred from the claim text.