| Project/Area Number |
26860075
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Antibody drug conjugate / Dendrimer / Bioconjugation / click conjugation / endosomal escape / scFv antibody fragment / siRNA / 薬学 / svFV antibody fragment / Herceptin / PAMAM / Transglutaminase / Homogeneous conjugate / monoclonal antibody / Antibody Drug Conjugate |
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| Outline of Final Research Achievements |
In this research, an approach to use antibody-polycationic compound as a delivery vehicle for therapeutic oligonucleotides like siRNA has been proposed. Due to its high loading capacity and well-defined structure, polyamidoamine (PAMAM) was selected as a polycationic compound, which can efficiently carry siRNAs and help release of the payload in target cells. As a target specific ligand, Herceptin was used which is a humanized monoclonal antibody designed to target HER 2 found in breast cancer. Three strategies were attempted to conjugate the antibody and PAMAM. Attempts were also made to synthesize homogenous bioconjugates with defined ratio of antibody and PAMAM. Preliminary cell assay indicated possibility of non-specific interaction of the bioconjugate toward target cells. Further consideration is needed to avoid non-specific interaction towards healthy cells along with controlled loading of siRNA and to improve delivery potential towards target cancer cells.
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