Development of PI polyamide targeting Sar1b gene

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461378
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Nihon University
• Principal Investigator: UENO Takahiro 日本大学, 医学部, 兼任講師 (40386008)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Sar1b / PI polyamide / カイロミクロン / 肥満 / 脂質異常症

Outline of Final Research Achievements

Pyrrole-imidazole polyamides (PI polyamides) are effective inhibitors of tissue specific and general transcription factors. Sar1b play a major role in chylomicron synthesis in small intestine. We designed and synthesized PI polyamide targeting Sar1b gene to reduce intestinal chylomicron synthesis. Treatment of CaCo2 cells with 0.1μM PI polyamide significantly reduced Sar1b mRNA expression. PI polyamide significantly decreased Sar1b mRNA in the small intestine of Wistar rats. Body weights of rats treated with PI polyamide were significantly lower compared with that in control rats at the end of the treatment.
This noel therapeutic agent, PI polyamide, decreased Sar1b expression in vivo. PI polyamide targeting Sar1b gene has a possibly to be a useful tool for the new strategy for transcription regulation therapy.

Free Research Field

脂質代謝