Glypican-3-specific modified aptamer and use thereof
Provided are a glypican-3 (GPC3)-specific modified aptamer, and prevention or treatment of hepatoma using the same. The glypican-3-specific modified aptamer of the present invention specifically binds to glypican-3 to be internalized into hepatoma cells, and exhibits anticancer activity through an anticancer agent bound to the aptamer, and therefore, has a selective anticancer effect only for GPC3-expressing hepatoma cells without affecting normal hepatocytes.
1 . A modified aptamer comprising a nucleic acid aptamer specifically binding to glypican-3 (GPC3) and an anticancer agent, wherein the nucleic acid aptamer consists of any one selected from the group consisting of SEQ ID NO: 6 to SEQ ID NO: 11 and SEQ ID NO: 13 to SEQ ID NO: 25.
2 . The modified aptamer of claim 1 , wherein one or more anticancer agents are bound to the nucleic acid aptamer.
3 . The modified aptamer of claim 2 , wherein the anticancer agents are bound by substituting any one or more bases in the nucleotide sequence of the nucleic acid aptamer.
4 . The modified aptamer of claim 3 , wherein the base is cytosine or guanine.
5 . The modified aptamer of claim 2 , wherein the anticancer agent is any one or more selected from the group consisting of gemcitabine, cytarabine, carboplatin, cisplatin, crizotinib, cyclophosphamide, docetaxel, doxorubicin, erlotinib, etoposide, 5-fluorouracil (5-FU), imatinib mesylate, irinotecan, liposome-encapsulated doxorubicin, methotrexate, paclitaxel, sorafinib, sunitinib, topotecan, trabectidin, vincristine, and vinblastine.
6 . The modified aptamer of claim 5 , wherein the anticancer agent is gemcitabine.
7 . A pharmaceutical composition for preventing or treating hepatoma, the pharmaceutical composition comprising the modified aptamer of claim 1 as an active ingredient.
8 . A nucleic acid aptamer specifically binding to glypican-3, the nucleic acid aptamer consisting of any one nucleotide sequence selected from the group consisting of SEQ ID NO: 6 to SEQ ID NO: 11 and SEQ ID NO: 13 to SEQ ID NO: 25.
9 . A composition for detecting glypican-3, the composition comprising the nucleic acid aptamer of claim 8 as an active ingredient, wherein the nucleic acid aptamer is conjugated to a detectable label.
10 . A method of detecting glypican-3, the method comprising, in order to provide information needed for diagnosis or prognosis of hepatoma:
detecting a content of glypican-3 in a biological sample derived from a test subject using the composition for detecting of claim 9 ;
comparing the result of detecting the content with the result of detecting a content of glypican-3 in a control sample; and
associating the subject with diagnosis or prognosis of hepatoma, when a change in the content in the sample derived from the subject is observed, as compared with the control sample.
11 . A kit for diagnosing hepatoma, the kit comprising
(a) the composition for detecting of claim 9 ,
(b) one or more of a buffer, a control sample, and instructions for use.