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2014 Fiscal Year Final Research Report

Owing to the development of RNA medicine, discovery of practical RNA molecules and synthesis of nucleic acid PET probes

Research Project

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Project/Area Number 24390025
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Drug development chemistry
Research InstitutionGifu University

Principal Investigator

KITADE Yukio  岐阜大学, 工学部, 教授 (20137061)

Project Period (FY) 2012-04-01 – 2015-03-31
KeywordsRNA創薬 / オリゴヌクレオチド / クリック反応 / ラベル標識化 / 薬物動態 / PETプローブ / バイオイメージング / ドラッグデリバリー
Outline of Final Research Achievements

Ethynylbenzene-substituted glycol, as a versatile crick-reaction probe, was synthesized and their RNA post-labeling property was investigated. Stereoselective synthesis of 1-deoxy-1-ethynyl-β-D-ribofuranose was performed for RNA labeling. SiRNAs and miRNAs bearing urea/thioures-bridged aromatic compounds at their 3'-end were also prepared and these dsRNAs definitely showed nuclease resistance. Oligonucleotides with glucosamine at the 3'-position were synthesized reaction and their biological activity was investigated. Some of chemically modified siRNAs at the 3’-position showed avoidance of off-target effect.
Chemically modified synthetic miRNA-205 inhibited the growth of melanoma cells in vitro and in vivo. A clinical trial of miR-205 against canine melanoma is now in progress; thus far, intratumoral injection of miR-205 into a recurrent tumor derived from naturally occurring canine melanoma has resulted in complete remission in 2 of 5 cases.

Free Research Field

医歯薬学

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Published: 2016-06-03  

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