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Treatment of renal fibrosis by short miRNA mimic

Research Project

Project/Area Number 17K16101
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionTokyo Medical University

Principal Investigator

Saito Suguru  東京医科大学, 医学部, 臨床研究医 (30793385)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords腎線維症 / AAV / micro RNA / miR-29b / miRNA / 腎臓学 / 核酸医薬 / microRNA
Outline of Final Research Achievements

Renal fibrosis is a common feature of CKD, which has no available specific treatment. Previous studies showed that miR-29b inhibits renal fibrosis in mice models. However, an efficient method of kidney-targeted miRNA delivery has yet to be established.
Recombinant adeno-associated virus (rAAV) vectors have great potential for clinical application. The distinct AAV serotypes exhibit different tissue tropisms. For kidney-targeted gene delivery, the most suitable AAV serotype has yet to be established. We found that rAAV6 vector is the most suitable for targeting kidney cells regardless of animal species in vitro and rAAV6 is the most suitable vector for kidney-targeted in vivo gene delivery in mice. Intra-renal pelvic injection of rAAV vectors can transduce genes into kidney TECs. Furthermore, rAAV6-mediated miR-29b delivery attenuated renal fibrosis in UUO model by suppressing Snail1 expression.

Academic Significance and Societal Importance of the Research Achievements

腎間質線維化は糖尿病,高血圧など様々な病態が原因とされており,一度起きた線維化は不可逆的である.一般に慢性腎臓病の初期は糸球体病変であり、これに対しては様々な治療法が存在するが,その後進行が進み,間質線維化が病態の中心になると,人工透析導入の大きな原因となっている.そのため腎間質線維化の抑制を治療目標とすることで,将来的に人工透析導入数の減少を目指すことが可能であると考える.
本研究の成果により,腎線維症の治療法としてmiRNA補充療法を実用化するための可能性を見い出せたと考える.またAAVは臨床応用可能なウイルスベクターであり,腎臓への遺伝子治療においても意義ある成果を残せたと考える.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (4 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] rAAV6-mediated miR-29b delivery suppresses renal fibrosis.2019

    • Author(s)
      Saito S, Ohno SI, Harada Y, Oikawa K, Fujita K, Mineo S, Gondo A, Kanno Y, KurodaM.
    • Journal Title

      Clin Exp Nephrol.

      Volume: 23 (12) Issue: 12 Pages: 1345-1356

    • DOI

      10.1007/s10157-019-01783-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] rAAV6-mediated miR-29b delivery suppresses renal fibrosis2018

    • Author(s)
      Suguru Saito
    • Organizer
      American Society of Nephrology Kidney Week
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] AAV6ベクターを介したmiR-29b補充療法による腎線維化の抑制2018

    • Author(s)
      齋藤 優
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] AAV-mediated miR-29b delivery suppress renal fibrosis2017

    • Author(s)
      齋藤 優
    • Organizer
      第9回RNAi研究会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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