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STUDY OF BINDING ABILITY OF PHOSPHOROTHIOATE OLIGONUCLEOTIDES WITH PROTEIN

Research Project

Project/Area Number 08670540
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionSt.Marianna University School of Medicine

Principal Investigator

SHOJI Yoko  St.Marianna University School of Medicine Department of Microbiology, Assistant Professor, 医学部, 講師 (00235714)

Co-Investigator(Kenkyū-buntansha) MIZUSHIMA Yutaka  St.Marianna University School of Medicine Institute of Medical Science, Professo, 難病治療研究センター, 教授 (40010409)
SHIMADA Jingoro  St.Marianna University School of Medicine Department of Microbiology, Professor, 医学部, 教授 (50056701)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Keywordsoligonucleotides / phosphorothioate / phosphodiester / anti-herpetic activities / cationic liposomes / フォスフォロチオエート / オリゴヌクレオチド / 抗ヘルペス効果 / カチオン性リポソーム / S-oligo / HSV-I / G4重鎖構造 / D-oligo / ヘルペスウイルス
Research Abstract

We've recognized that phosphorothioate oligonucleotides (S-ODN) showed potent anti-herpetic activities when target site was limited near the splicing site. It was implied that S-ODN interfered the conservative structure which could be essential for the splicing, thus showed potent anti-herpetic activities. This was one explanation why S-ODN targeted splicing site showed potent anti-herpetic activities. However, it has been reported that G rich sequences reveal sequence non-specific biological activities. S-ODN may reveal another mechanism which might be based on strong protein binding activities. S-ODN strongly bound to serum protein at the ratio of 86.6%, while 21.6% for phosphodiester oligonucleotides (D-ODN). Binding activities which directly bound to the virus was more than 50% for S-ODN, on the other hand it was less than 5% for D-ODN.
Thirteen mer S-ODN showed inhibitory effect on virus entry into the cell at the early stage of infection, while D-ODN did not. CD spectrum of S-ODN implied G-quartet structure, however, the relation between biological activities and higher dimension structure could not be clear.
Moreover, we tried to enhance the anti-herpetic activities of S-ODN by using cationic liposomes. Cationic liposomes is useful tool to enhance the anti-herpetic activities of D-ODN, while it was not the case for SOD.One of the reason might be strong protein binding activities of S-ODN.From this study, the caution is proposed when S-ODN containing G-rich sequences might involve another mechanism other than antisense manner. We should carefully select the drug delivery system to enhance the biological activities of S-ODN.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report

Research Products

(32 results)

All Other

All Publications

  • [Publications] 岩谷若夫、東海林洋子、他: "抗HSV活性を有するアンチセンス・オリゴDNAの安定性およびウイルス感染細胞における動態の検討" Drug Delivery System. 11. 427-434 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji Y.et al.: "Cellular uptake and biological effects of antisenese oligodeoxynucleotide analogs targeted to herpes simplex virus." Antimicrob. Agents Chem.40. 1670-1675 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 東海林洋子、他: "VEGF mRNAに対するヒト臍帯静脈細胞の管腔形成抑制の効果をカチオン性リポソームが増強" Drug Delivery System. 12. 187-192 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji Y.et al.: "Enhancement of anti-herpetic activity of antisense phosphorothioate oligonucleotides 5'end modified with geranoil." J.Drug Targeting. 5(4). 261-273 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 東海林洋子、他: "オリゴヌクレオチドの抗ヘルペス効果-PCR法による判定-" 日本化学療法学会誌. 46(9). 363-367 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji Y.et al.: "Limited usage of cationic liposomes as tools to enhance the anti-herpetic activities of oligonucleotides in Vero cells infected with herpes simplex virus type I" Antisense Nucleic Acid Drug Dev.8(4). 255-263 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji Y.et al.: "Anti-HIV activity of phosphorothioate oligodeoxynucleotides containing consecutive G sequences" Int.J.Immunotherapy. XII(1/2). 1-9 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji Y.et al.: "Cellular uptake and biological effects of antisense oligodexynucleotides analogs targeted to herpes simplex virus." Antimicrob.Agents Chem.40. 1670-1675 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji Y.et al.: "Enhancement of anti-herpetic activity of antisense phosphorothioate oligonucleotides 5' end modified with geraniol." 23rd International Symposium on Controlled Release of Bioactive Materials.263-264 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sato T., Shoji Y.et al.: "DNA hybrid complexes with glutamic acid derivatives and their applications to gene delivery system." 23rd International Symposium on Controlled Release of Bioactive Materials.895-896 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koyama Y., Shoji Y.et al.: "Novel poly (ethyleneglycol) derivatives having pendant amino groups : aggregation of its acids and amphiphilic polyion complex with fatty the application to DNA delivery." 23rd International Symposium on Controlled Release of Bioactive Materials.897-898 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji Y., et al.: "Enhancement of anti-herpetic activity of antisense phosphorothioate oligonucleotides 5' end modified with geraniol." J.Drug Targeting. 5(4). 261-273 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji Y., et al.: "Limited usage of cationic liposomes as tools to enhance the anti-herpetic activities of oligonucleotides in Vero cells infected with herpes simplex virus type I." Antisense Nucleic Acid Drug Dev.8(4). 255-263 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji Y., et al.: "Characteristics of oligonucleotides entrapped into liposumal formulations." 25rd International Symposium on Controlled Release of Bioactive Materials.346-347 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji Y.et al: "Enhancement of anti-herpetic activity of antisense phosphorothioate oligonucleotides 5'end modified with geraniol." J.Drug Targeting. 5(4). 261-273 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 東海林洋子、他: "遺伝子医薬品の研究動向" 日本臨床. 56(8). 238-247 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 東海林洋子: "Gene Therapyにおける製剤設計" 日本薬剤学会誌. 14(2). 6-7 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 東海林洋子: "遺伝子医薬品のドラッグデリバリーシステム" Antisense. 1(2). 50-56 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 東海林洋子、他: "オリゴヌクレオチドの抗ヘルペス効果-PCR法による判定-" 日本化学療法学会誌. 46(9). 363-367 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shoji Y.et al.: "Limited usage of cationic liposomes as tools to enhance the anti-herpetic activities of oligonucleotides in Vero cells infected with herpes simplex virus type l." Antisense Nucleic Acid Drug Dev.8(4). 255-263 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 東海林洋子,他.: "VEGFmRNAに対するアンチセンスDNAとヒト膵帯静脈細胞の管腔形成抑制効果をカチオン性リボソームが増強" Drug Delivery System. 12(3). 187-192 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 東海林洋子: "遺伝子医薬品のドラッグデリバリーシステム." Antisense. 1(2). 50-56 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato T., Shoji Y.,et al.: "Characterization,cell uptake,and subcellular distribution of DNA complexes with lipoglutamides having tetraethylene glycol tails." J.Biomaterial Science Polymenr Edition. 9. 31-42 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 東海林洋子: "Gene therapyにおける製剤設計." 日本薬剤学会会報. 14(2). 6-7 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shoji Y.,et al.: "Limited usage of cationic liposomes as tools to enhance the anti-herpetic activities of oligonuclcotides in Vero cells infected with herpes simplex virus type I." Antisense and Nucleic Acid Drug Dev.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] 東海林洋子,他.: "オリゴヌクレオチドの抗ヘルペス効果-PCR法による判定-" 日本化学療法学会. (印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] 東海林洋子、他。: "アンチセンスオリゴヌクレオチドの家兎ヘルペス角膜炎に対する効果の基礎的検討。" Jpn Clin Pharmacol Ther. 27. 309-310 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shoji Y.,et al.: "Cellular uptake and biological effects of antisense ologodeoxynucleotides analogs targeted to herpes simplex virus." Antimicrob. Agents Chem.40. 1670-1675 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 岩谷若夫、東海林洋子、他: "抗HSV活性を有するアンチセンス・オリゴDNAの安定性およびウイルス感染細胞における動態の検討。" Drug Delivery System. 11. 427-434 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Shoji,et al.: "Anti-HIV activity of phosphorothioate oligodeoxynucleotides containing consecutive G sequences" Int. J. Immunotherapy. XII (1/2). 1-9 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shoji,Y.et al.: "Enhancement of anti-herpetic activity of antisense phosphorothioate oligonucleotides 5' end modified with geraniol." Drug Targeting. (in press)

    • Related Report
      1996 Annual Research Report
  • [Publications] 東海林洋子、他: "VEGF mRNAに対するアンチセンスDNAのヒトさい帯静脈の管腔形成抑制効果をカチオン性リポソームが増強。" Drug Delivery System. (in press).

    • Related Report
      1996 Annual Research Report

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Published: 1996-03-31   Modified: 2016-04-21  

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