| Project/Area Number |
15K12542
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
眞鍋 史乃 国立研究開発法人理化学研究所, 主任研究員研究室等, 専任研究員 (60300901)
富 海英 大阪大学, 医学系研究科, 特任助教 (70754646)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 抗体薬物複合体 / 遺伝子治療 / siRNA / 心不全 / 抗体核酸複合体 / ADC / 遺伝子デリバリー |
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| Outline of Final Research Achievements |
To realize the safety and efficiently gene therapy for severe heart failure (HF), we developed a novel antibody gene conjugate using antibody to the extracellular domain of HB-EGF, which had been reported to be upregulated in HF. Using polypeptide linker composed of pH-dependent fusogenic peptide of influenza hemagglutinin 2 (HA2) and dipeptide of endosomal protease cathepsin recognition site, we successfully developed an anti-HB-EGF antibody-siRNA conjugate that showed efficient endosome escape capability and elevated knockdown efficiency in vitro. In addition, immunofluorescent microscopy and flow cytometry analysis suggested that cardiac fibroblasts are potential targets for gene therapy in HF with anti-HB-EGF antibody-siRNA conjugate.
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