| Budget Amount *help |
¥47,840,000 (Direct Cost: ¥36,800,000、Indirect Cost: ¥11,040,000)
Fiscal Year 2014: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2013: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2012: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2011: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
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| Outline of Final Research Achievements |
(1) MicroRNA (miR)-122 is highly expressed in liver and controls cholesterol metabolism. We prepared antisense molecules (AMO) against miR-122 using nuclease resistant 2’-OMe-4’-thioribonucleosides. YSK05-liposome was prepared with the pH-sensitive cationic lipid, and the AMO was encapsulated. Systemic administration of the liposome induced knockdown of miR-122 and increase in target genes in the liver, and a subsequent reduction in plasma cholesterol at a dose of 1mg AMO/kg with persisting for over 2 weeks. (2) Prostate-specific membrane antigen (PSMA) ligand (GL) was attached to a dumbbell-type of the cyclic oligonucleotide (fCpG-dmDNA), which contained 5-formylCpG, giving GL-fCpG-dmDNA. fCpG-dmDNA inhibited the methylation of CpG-oligonucleotides. fCpG-dmDNA showed cytotoxicity against HeLa cells (PSMA-negative) with an IC50 value of 41 nM. On the other hand, GL-fCpG-dmDNA showed cytotoxicity against only PSMA-positive cell line such as LNCaP prostate tumor cells.
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