2013 Fiscal Year Final Research Report

Development of increasing functional HDL-C using antisense oligonucleotides as innovative therapy

Research Project

Project/Area Number	23591109
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Circulatory organs internal medicine
Research Institution	National Cardiovascular Center Research Institute
Principal Investigator	IWAMOTO Noriyuki 独立行政法人国立循環器病研究センター, 研究所, 客員研究員 (70534709)
Project Period (FY)	2011 – 2013
Keywords	HDL / ABCA1 / 核酸医薬
Research Abstract	The objective of this basic research is to analyze whether or not innovative antisense oligonucleotides targeted specific molecular gene would be candidate of increasing serum HDL-cholesterollevel through the ABCA1/apoA-I pathway. We previously demonstrated that transcription factor AP-2 negatively regulates the ATP-binding cassette A1 (ABCA1) gene through its Ser-phosphorylation by protein kinase PKD which is a common modulator of the DNA binding activity of AP-2 through their phosphorylation for negative regulation of the ABCA in genes expression. The Antisense oligoniculeotide modified BNA is so innovative that have stronger effective compared to previous one. In this study, we demonstrated that the PKD specific targeted antisense could increase ABCA1 mRNA levels in liver in vitro and in vivo, which result in raising serum HDL-C level in vivo. To further develop this strategy, we need more experiments to figure out the value of efficacy and safety using oligonucleotides therapy