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Naked antisense double-stranded DNA oligonucleotide efficiently suppresses BCR-ABL positive leukemic cells

発表形態:
原著論文
主要業績:
主要業績
単著・共著:
共著
発表年月:
2020年08月
DOI:
10.1007/s10637-019-00862-9
会議属性:
指定なし
査読:
有り
リンク情報:

日本語フィールド

著者:
Toshimi Hoshiko, Yasushi Kubota, Takuya Akisawa, Tatsuro Watanabe, Kazuaki Tanigawara, Junichi Yano, Shinya Kimura
題名:
Naked antisense double-stranded DNA oligonucleotide efficiently suppresses BCR-ABL positive leukemic cells
発表情報:
Invest New Drugs 巻: 38 号: 4 ページ: 1012-1019
キーワード:
概要:
Oligonucleotide-based gene silencing, using molecules such as antisense oligonucleotides (ASOs), small interfering RNA, and aptamers, is widely studied. Another approach uses DNA/RNA heteroduplex oligonucleotides (HDOs). Here, we developed an antisense double-stranded DNA oligonucleotide (ADO) by modification of the complementary RNA in an HDO to generate DNA for increasing resistance to nucleases. Naked BCR-ABL-targeting ADO was significantly more potent than siRNA at reducing BCR-ABL chimeric mRNA expression in chronic myeloid leukemia (CML) cell lines. Further, naked BCR-ABL-targeting ADO suppressed BCR-ABL protein levels in a dose-dependent manner, inhibited CML cell proliferation, and augmented the inhibitory effects of imatinib mesylate. In conclusion, ADO technology is an attractive method for therapeutic application.
抄録:

英語フィールド

Author:
Toshimi Hoshiko, Yasushi Kubota, Takuya Akisawa, Tatsuro Watanabe, Kazuaki Tanigawara, Junichi Yano, Shinya Kimura
Title:
Naked antisense double-stranded DNA oligonucleotide efficiently suppresses BCR-ABL positive leukemic cells
Announcement information:
Invest New Drugs Vol: 38 Issue: 4 Page: 1012-1019
An abstract:
Oligonucleotide-based gene silencing, using molecules such as antisense oligonucleotides (ASOs), small interfering RNA, and aptamers, is widely studied. Another approach uses DNA/RNA heteroduplex oligonucleotides (HDOs). Here, we developed an antisense double-stranded DNA oligonucleotide (ADO) by modification of the complementary RNA in an HDO to generate DNA for increasing resistance to nucleases. Naked BCR-ABL-targeting ADO was significantly more potent than siRNA at reducing BCR-ABL chimeric mRNA expression in chronic myeloid leukemia (CML) cell lines. Further, naked BCR-ABL-targeting ADO suppressed BCR-ABL protein levels in a dose-dependent manner, inhibited CML cell proliferation, and augmented the inhibitory effects of imatinib mesylate. In conclusion, ADO technology is an attractive method for therapeutic application.


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