RNA aptamer specifically binding to carcinoembryonic antigen and use thereof
View Patent ↗Provided are RNA aptamer specifically binding to cancer metastasis-inducing domain of CEA (Carcinoembryonic antigen), a composition for prevention and/or inhibition and/or diagnosis of cancer metastasis containing the same as an active ingredient, and a method of prevention and/or inhibition and/or diagnosis of cancer metastasis using the same.
1. A method for preventing or inhibiting cancer metastasis, the method comprising administering an RNA aptamer to a patient in need of inhibition of metastasis,
wherein the RNA aptamer is 35 to 49 bases in length and binds to a linkage region between N domain and A1 domain of carcinoembryonic antigen (CEA), and the RNA aptamer comprises continuous 35 or more bases comprising the nucleotide sequence from 9 th to 43 rd positions of following SEQ ID NO: 13:
<SEQ ID NO: 13>
GCGGAAGCGUGCUGGGCUAGAAUAAUAAUAAGAAAACCAGUACUUUCGU; and
wherein C_(cytosine) and U_(uracil) in the RNA aptamer is modified by substituting 2′ hydroxyl group with fluoro group.
2. The method according to claim 1 , wherein the RNA aptamer comprises the nucleotide sequence of SEQ ID NO: 14.
3. The method according to claim 1 , wherein the cancer is selected from the group consisting of colon cancer, stomach cancer, pancreatic cancer, and lung cancer.
4. The method according to claim 1 , wherein the cancer metastasis is a cancer metastasis to liver.
5. The method according to claim 1 , wherein the RNA aptamer is modified by at least one method selected from
conjugating with polyethyleneglycol or cholesterol at 5′ end; and
attaching idT (inverted deoxy thymidylate) at 3′ end.
6. The method according to claim 5 , wherein the RNA aptamer comprises the nucleotide sequence of SEQ ID NO: 13 or 14.
7. The method according to claim 5 , wherein the cancer is selected from the group consisting of colon cancer, stomach cancer, pancreatic cancer, and lung cancer.
8. The method according to claim 5 , wherein the cancer metastasis is a cancer metastasis to liver.
9. The method according to claim 5 , wherein
the RNA aptamer consists of the nucleotide sequence of SEQ ID NO: 13;
the RNA aptamer is modified by conjugating with polyethyleneglycol at 5′ end and attaching idT (inverted deoxy thymidylate) at 3′ end.
10. The method according to claim 1 , wherein the RNA aptamer consists of the nucleotide sequence of SEQ ID NO: 13 in which C (cytosine) and U (uracil) are modified by substituting 2′ hydroxyl group with fluoro group.
11. The method according to claim 1 , wherein the RNA aptamer consists of the nucleotide sequence of SEQ ID NO: 14 in which C (cytosine) and U (uracil) are modified by substituting 2′ hydroxyl group with fluoro group.
12. A method for preventing or inhibiting cancer metastasis, comprising administering an RNA aptamer to a patient in need of inhibition of metastasis,
wherein:
the RNA aptamer binds to a linkage region between N domain and A1 domain of carcinoembryonic antigen (CEA) and comprises continuous 35 or more bases comprising the nucleotide sequence from 9 th to 43 rd positions of following SEQ ID NO: 13:
<SEQ ID NO: 13>
GCGGAAGCGUGCUGGGCUAGAAUAAUAAUAAGAAAACCAGUACUUUCGU;
the RNA aptamer is modified by at least one method selected from conjugating with polyethyleneglycol or cholesterol at 5′ end; and attaching idT (inverted deoxy thymidylate) at 3′ end;
the RNA aptamer consists of the nucleotide sequence of SEQ ID NO: 13; and
C (cytosine) and U (uracil) in the RNA aptamer is modified by substituting 2′ hydroxyl group with fluoro group.