Aptamer for IL-21 and use thereof
The present invention provides an aptamer that binds to IL-21, an aptamer that binds to IL-21 and inhibits the binding of IL-21 and a receptor thereof, and an aptamer that binds to IL-21 and contains a nucleotide sequence represented by the formula (1): CGRYKACY wherein R is A or G, Y is C or U, and K is G or U.
1 . An aptamer comprising the nucleotide sequence of SEQ ID NOs: 1-5, 7, 20-29, or 31-43 provided that uracil (U) is optionally thymine (T),
wherein the nucleotide sequence of SEQ ID NOs: 1-5, 7, 20-29, or 31-43 is represented by the following formulas (1) to (3):
formula (1) is CGRYKACY,
formula (2) is CCKYC,
formula (3) is GYMCG,
wherein formulas (1) to (3) are arranged to comprise the order of formula (2), formula (1), and formula (3) from the 5′-terminal side,
wherein R is A or G, Y is Cor U, K is G or U, and M is A or C, and
wherein the aptamer binds to interleukin-21 and inhibits binding between the interleukin-21 and a interleukin-21 receptor.
2 . The aptamer according to claim 1 , wherein, at the 1st C in the formula (1), the hydroxy group at the 2′-position of ribose is substituted by a fluoro group.
3 . The aptamer according to claim 1 wherein a nucleotide contained in the aptamer,
(i) a hydroxy group at the ribose 2′-position of each pyrimidine nucleotide contained in the aptamer is the same or different, and unsubstituted or substituted by an atom or a group selected from the group consisting of a hydrogen atom, a fluorine atom, and a methoxy group,
and wherein in the aptamer of (i),
(ii) a hydroxy group at the ribose 2′-position of each purine nucleotide contained in the aptamer is the same or different, and unsubstituted or substituted by an atom or a group selected from the group consisting of a hydrogen atom, a methoxy group, and a fluorine atom.
4 . The aptamer according to claim 1 , wherein, at the C at position 4 in the formula (3): GYMCG, the hydroxy group at the 2′-position of ribose is substituted by a fluoro group.
5 . A complex comprising the aptamer according to claim 1 and a functional substance, wherein the functional substance is an affinity substance, a labeling, substance, an enzyme, a drug delivery vehicle, or a drug.
6 . A medicament comprising the aptamer according to claim 1 .
7 . A method for the treatment or prophylaxis of pulmonary hypertension, the method comprising administering the medicament of claim 6 to a subject in need thereof.