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Spatially and temporally regulated gene therapy using stress response promoter in retinal injury

Research Project

Project/Area Number 16K20301
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionTohoku University

Principal Investigator

Fujita Kosuke  東北大学, 医学系研究科, 助手 (80708115)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords遺伝子治療 / 緑内障 / アデノ随伴ウイルス
Outline of Final Research Achievements

Retinal ganglion cell (RGC) degeneration is believed to underlie many ocular diseases including glaucoma. In these diseases, RGCs are affected unevenly, both spatially and temporally, such that healthy and unhealthy RGCs coexist in different patterns at different time points. We describe a temporally and spatially regulated AAV gene therapy aiming to reduce undesired off-target effects on healthy RGCs. The Mcp-1 promoter shown to be transcribed in stressed RGCs following murine optic nerve injury was combined with the neuroprotective transcription factor NRF2. In this model, Mcp-1-driven NRF2 expression targeting only stressed RGCs showed efficacy equivalent to non-selective CMV promoter-driven therapy for preventing RGC death. However, CMV promoter-mediated NRF2 transcription induced cellular stress responses and death of uninjured RGCs. Combining a stress-responsive promoter and therapeutic gene is a versatile strategy for specifically targeting cells at risk of degeneration.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (1 results)

All 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Spatially and Temporally Regulated NRF2 Gene Therapy Using Mcp-1 Promoter in Retinal Ganglion Cell Injury2017

    • Author(s)
      Fujita Kosuke、Nishiguchi Koji M.、Shiga Yukihiro、Nakazawa Toru
    • Journal Title

      Molecular Therapy Methods & Clinical Development

      Volume: 5 Pages: 130-141

    • DOI

      10.1016/j.omtm.2017.04.003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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