Sequence-specific read through of premature termination codon

2014 Fiscal Year Final Research Report

• 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
• Keywords: アミノグリコシド / PTC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.

Free Research Field

生物有機化学