2016 Fiscal Year Final Research Report
Development of a novel antibody gene complex for the gene therapy of heart failure.
| 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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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | 抗体薬物複合体 / 遺伝子治療 / siRNA / 心不全 |
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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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| Free Research Field |
DDS 、循環器内科、抗体薬物複合体、遺伝子治療
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