Investigation of nucleic acid type ligand which can use in vivo

• Project/Area Number: 23700552
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Hokkaido University
• Principal Investigator: HYODO Mamoru 北海道大学, 大学院・薬学研究院, 特任助教 (30548186)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: バイオコンジュゲート材料 / アプタマー / リガンド / DDS / 腫瘍血管内皮細胞 / active targeting / Troponin T / リポソーム / SELEX / 脈管形成阻害 / 内在化

Research Abstract

We have isolated the DNA aptamer named AraHHOOI from 12rounds of selection to tumor endothelial cells and counter selection with normal endothelialcells and tumor parenchymal cells. AraHHOOl aptamer showed 44 nM dissociationconstant to tumor endothelial cells and incorporated into tumor endothelial cells.AraHHOOI aptamer binds to Troponin T protein on tumor endothelial cells and AraHHOOlaptamer bound liposome showed 3.5 times higher uptake efficacy compared to normalliposome.

Research Products

• [Journal Article] Development of a novel DNAaptamer ligand targeting to primary culturedtumor endothelial cells by a cell-based SELEXmethod (2012)
  • Author(s): Mst. Naznin Ara, Mamoru Hyodo,Noritaka Ohga, Kyoko Hida, Hideyoshi Harashima
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and gene silencing activity in vitro and in VIVO (2012)
  • Author(s): 2. Sato Y, Hatakeyama H, Sakurai Y Hyodo M, Akita H, Harashima H
  • Journal Title: Journal of Controlled Release Volume: 163 Issue: 3 Pages: 267-276
  • DOI: 10.1016/j.jconrel.2012.09.009
  • Peer Reviewed
• [Journal Article] Vascular-targeted nanotherapy for obesity” Unexpected passive targeting mechanism to obese fat for the enhancement of active drug delivery. (2012)
  • Author(s): Hossen Md. Nazir
  • Journal Title: Journal of Controlled Release Volume: 163 Issue: 2 Pages: 101-110
  • DOI: 10.1016/j.jconrel.2012.09.002
  • Peer Reviewed
• [Journal Article] Identification of ligand Analogues that control c-di-GMP Riboswitches (2012)
  • Author(s): Kazuhiko Furukawa
  • Journal Title: ACS Chem. Biol. Volume: 7 Issue: 8 Pages: 1436-1443
  • DOI: 10.1021/cb300138n
  • Peer Reviewed
• [Journal Article] Development of a novel DNA aptamer ligand against primary cultured tumor endothelial cell (2012)
  • Author(s): Naznin Ara.
  • Journal Title: PLoS ONE Volume: 7(12) Issue: 12 Pages: e50174-e50174
  • DOI: 10.1371/journal.pone.0050174
  • Peer Reviewed
• [Journal Article] STING is a direct innate imune sensor of cyclic di-GMP. (2011)
  • Author(s): Dara L. Burdette, Kathryn M. Monroe, Katia Sotelo-Troha, Jeff S. Iwig, Barbara Eckert, Mamoru Hyodo, Yoshihiro Hayakawa, Russell E. Vance
  • Journal Title: Nature Volume: 478 Issue: 7370 Pages: 515-519
  • DOI: 10.1038/nature10429
  • Peer Reviewed
• [Presentation] 新規アジュバント c-di-GMP の効率的DDSの創製 (2013)
  • Author(s): 宮部寛子
  • Organizer: 日本薬学会第１３３回年会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Isolation ofnew DNA aptamers for pancreatic cancer cells.Abstract (2012)
  • Author(s): Mamoru Hvodo, Mst. Naznin Ara, YusukeTakaya and Hideyoshi Harashima
  • Organizer: IS3NA XX intemationalroundtable
  • Place of Presentation: Centre Mont-Royal, Montreal,Canada
• [Presentation] Investigation of RNA aptamers targetingmitochondria by mitochondria based SELEX.Abstract No.149 (2012)
  • Author(s): Yuri Tawaraya, Mamoru Hyodo, YumaYamada and Hideyoshi Harashima
  • Organizer: IS3NA XX intemationalroundtable
  • Place of Presentation: Centre Mont-Royal Montreal,Canada
• [Presentation] ミトコンドリア標的RNAアプタマーの探索 (2012)
  • Author(s): 俵谷優里、兵膣宣,、山田勇磨、原島秀吉
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸国際会議場、神戸
• [Presentation] Development of a new DNA aptamer againstprimary cultured tumor endothelial cells by acell-based SELEX method to discover a newdrug delivery system, Abstract No.3886 (2012)
  • Author(s): Mst Naznin Ara, Mamoru HvodΩ, NoritakaOhga, Kyoko Hida, Hideyoshi Harashima
  • Organizer: AACR annual meeting 2012
  • Place of Presentation: McCormickPlace, Chicago, Illinois, USA
• [Presentation] Isolation of new DNA aptamers for pancreatic cancer cells (2012)
  • Author(s): Mamoru Hyodo
  • Organizer: IS3NA XX international roundtable
  • Place of Presentation: Centre Mont-Royal (Canada)
• [Presentation] Investigation of RNA aptamers targeting mitochondria by mitochondria based SELEX (2012)
  • Author(s): Yuri Tawaraya
  • Organizer: IS3NA XX international roundtable
  • Place of Presentation: Centre Mont-Royal (Canada)
• [Presentation] ミトコンドリア標的RNAアプタマーの探索 (2012)
  • Author(s): 俵谷優里
  • Organizer: 日本薬剤学会第２７年会
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] Development of a new DNA aptamer against primary cultured tumor endothelial cells by a cell-based SELEX method to discover a new drug delivery system
  • Author(s): Mst Naznin Ara, Mamoru Hyodo, Noritaka Ohga, Kyoko Hida, Hideyoshi Harashima
  • Organizer: AACR annual meeting 2012
  • Place of Presentation: McCormick Place (USA)
• [Patent(Industrial Property Rights)] トロポニンTと結合するDNA、これを用いた腫瘍組織における血管新生および/または脈管形成抑制剤ならびにこれを用いた細胞内へ目的物質が取り込まれることを促進する剤 (2012)
  • Inventor(s): アラ ナズニン,兵藤宣,畠山浩人,樋田京子,大賀則孝,原島秀吉
  • Industrial Property Rights Holder: バイオメッドコア,アラ ナズニン,兵藤立,畠山浩人,樋田京子,大賀則孝,原島秀吉
  • Filing Date: 2012-06-21
• [Patent(Industrial Property Rights)] トロポニンTと結合するDNA、これを用いた腫瘍組織における血管新生および／または脈管形成抑制剤ならびにこれを用いた細胞内へ目的物質が取り込まれることを促進する剤 (2012)
  • Inventor(s): アラ ナズニン
  • Industrial Property Rights Holder: バイオメッドコア
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-124073
  • Filing Date: 2012-06-21