Sequence-specific read through of premature termination codon

Research Project

Project/Area Number	25620122
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Bio-related chemistry
Research Institution	Nagoya University
Principal Investigator	HAGIHARA Shinya 名古屋大学, 理学研究科(WPI), 准教授 (80373348)
Project Period (FY)	2013-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords	アミノグリコシド / PTCリードスルー / 遺伝子疾患 / ナンセンス変異 / 遺伝子治療 / リードスルー
Outline of Final Research Achievements	A nonsense mutation is a genetic mutation, which replaces codon encoding an amino acid into premature termination codon (PTC). The presence of PTC results in the expression of truncated proteins and hence causes a variety of diseases such as Duchenne muscular dystrophy. Aminoglycoside-induced readthrough of PTC has potential for the treatment of these diseases. Aminoglycosides induce PTC readthorough by decreasing the accuracy of translation by binding to the decoding center of ribosome. A limitation of aminoglycoside as pharmacogenetic agents is risk of significant toxicity. The effect of aminoglycoside is not specific to PTC, causing incorporation of an incorrect amino acid at a sense codon. We examined to design a new molecule that induces gene- and sequence-specific readthrough of PTC by conjugating aminoglycoside with oligonucleotide.