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Trial to suppress gene expression in airway by intratracheal administration of dry-powdered siRNA

Research Project

Project/Area Number 22390165
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionHiroshima University

Principal Investigator

HATTORI Noboru  広島大学, 大学院・医歯薬保健学研究院, 准教授 (00283169)

Co-Investigator(Renkei-kenkyūsha) OKAMOTO Hirokazu  名城大学, 薬学部, 教授 (00308941)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2011: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2010: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
KeywordsRNA干渉 / GFP / 吸入療法 / RNA干渉 / GFP
Research Abstract

In the present study, we tried to determine whether intratracheal administration of dry powdered low-molecular-weight chitosan (LMWC)/siRNA complexes suppressed gene expression in murine lung. Dry powdered LMWC/siRNA targeting green fluorescent protein (GFP-siRNA) and Lewis lung carcinoma cells stably expressing GFP (LLC-GFP) were prepared. Dry powdered LMWC/GFP-siRNA complex was intratracheally administered to GFP transgenic mice and the C57BL/6 mice carrying lung metastatic tumors consisting of LLC-GFP cells. The fluorescence intensity in the lung tissue sections was analyzed with a fluorescence microscope. Intratracheal administration of dry powdered LMWC/GFP-siRNA complex was found to suppress the fluorescence level of bronchi, bronchiole, alveoli, and metastatic lung tumors consisting of LLC-GFP cells. The results of the present study suggest that LMWC is an effective carrier for siRNA delivery to the lung, and dry powdered LMWC/siRNA complexes maybecome a promising tool to knock-down a specific gene expression in various lung diseases.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (11 results)

All 2012 2011 2010

All Journal Article (11 results) (of which Peer Reviewed: 11 results)

  • [Journal Article] Krebs von den Lungen-6 (KL-6) is a prognostic biomarker in patients with surgically resected non-small cell lung cancer.2012

    • Author(s)
      Tanaka S, et al.
    • Journal Title

      International journal of cancer

      Volume: 130 Issue: 2 Pages: 377-387

    • DOI

      10.1002/ijc.26007

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PAI-1 promotes the accumulation of exudate macrophages and worsens pulmonary fibrosis following type II alveolar epithelial cell injury.2012

    • Author(s)
      Osterholzer JJ, et al.
    • Journal Title

      Journal of pathology

      Volume: 228 Issue: 2 Pages: 170-180

    • DOI

      10.1002/path.3992

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intra-airway administration of small interfering RNA targeting plasminogen activator inhibitor-1 attenuates allergic asthma in mice.2011

    • Author(s)
      Miyamoto S, Hattori N, Senoo T, Onari Y, Iwamoto H, Kanehara M, Ishikawa N, Fujitaka K, Haruta Y, Murai H, Yokoyama A, Kohno N.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol

      Volume: 301

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chitosan-interferon-β gene complex powder for inhalation treatment of lung metastasis in mice2011

    • Author(s)
      Okamoto H, Shiraki K, Yasuda R, Danjo K, Watanabe Y
    • Journal Title

      J Control Release

      Volume: 150 Pages: 187-195

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mucins carrying selectin ligands as predictive biomarkers of disseminated intravascular coagulation complication in ARDS2011

    • Author(s)
      Nakashima T, et al
    • Journal Title

      Chest

      Volume: 139 Issue: 2 Pages: 296-304

    • DOI

      10.1378/chest.09-3082

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intra-airway administration of small interfering RNA targeting plasminogen activator inhibitor-1 attenuates allergic asthma in mice2011

    • Author(s)
      Miyamoto S, et al
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol

      Volume: 301 Issue: 6 Pages: L908-L916

    • DOI

      10.1152/ajplung.00115.2011

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Levels of Surfactant proteins A and D, and KL-6 are elevated in the induced sputum of COPD ; a sequential sputum analysis2011

    • Author(s)
      Ishikawa N, et al
    • Journal Title

      Respiration

      Volume: 82 Issue: 1 Pages: 10-18

    • DOI

      10.1159/000324539

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Optimized pulmonary gene transfection in mice by spray-freeze dried powder inhalation2010

    • Author(s)
      Mohri K, Okuda T, Mori A, Danjo K, Okamoto H.
    • Journal Title

      J Control Release

      Volume: 144 Pages: 221-226

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of plasminogen activator inhibitor-1 by RNA interference attenuates pulmonary fibrosis.2010

    • Author(s)
      Senoo T, Hattori N, Tanimoto T, Furonaka M, Ishikawa N, Fujitaka K, Haruta Y, Murai H, Yokoyama A, Kohno N.
    • Journal Title

      Thorax

      Volume: 65 Pages: 334-340

    • NAID

      120002398984

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Productive cough is an independent risk factor for the development of COPD in former smokers.2010

    • Author(s)
      Yamane T, et al.
    • Journal Title

      Respirology

      Volume: 15 Pages: 313-318

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant promoter methylation of WIF-1 and SFRP1,2,4 genes in mesothelioma.2010

    • Author(s)
      Kohno H, et al.
    • Journal Title

      Oncology Reports

      Volume: 24 Pages: 423-431

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed

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Published: 2010-08-23   Modified: 2019-07-29  

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