| Project/Area Number |
24659262
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied pharmacology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ITOH Kohji 徳島大学, ヘルスバイオサイエンス研究部, 教授 (00184656)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | リソソーム病 / in vivoイメージング / 酵素トラフィッキング / 疾患特異的iPS細胞 / 酵素補充療法 / GM2ガングリオシドーシス / ドラッグデリバリー / 酸性pH活性化蛍光プローブ / 酵素トラフィキング / iPS細胞 / 糖鎖レセプター / シグナル伝達 / 単球/マクロファージ |
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| Research Abstract |
We studied on intracellular traffic abnormality in lysosomal beta-hexosaminidase (Hex) deficiencies including Tay-Sachs disease (TSD) and Sandhoff diseases (SD) to develop novel enzyme replacement therapy based on techniques to promote delivery of recombinant Hex to lysosomes when extracellularly administrated. We developed modified Hex with high content of mannose 6-phospahte (M6P) residues, which were efficiently incorporated by disease-model cultured cells via cell surface M6P receptors. In addition, we established an iPS cell line derived from a TSD patient, and examined conditions under which neural cells including neural stem cells (NSC) and neural progenitor cells (NPC) could be induced from the TSD iPS cells. Furthermore, we developed novel fluorescent probes including Rhodol beta-GlcNAc as an artificial substrate for intracellular Hex activity and acidic pH-activatable fluorescent Rh-PM for in vivo imaging to detect lysosomal distribution of recombinant Hex.
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