Development of animal models for safety assessment of drugs using genome editing technology and its application

• Project/Area Number: 15K14854
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: The University of Tokyo
• Principal Investigator: KUWAHARA MASAYOSHI 東京大学, 大学院農学生命科学研究科(農学部), 教授 (30205273)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 安全性薬理 / ウサギ / Kcnq1遺伝子 / ゲノム編集技術 / 薬剤誘発性QT延長症候群

Outline of Final Research Achievements

The prolongation of the QT interval corresponding to the time from the start to the end of ventricular excitation in the electrocardiogram has attracted attention as a congenital and acquired long QT syndrome in humans. It is considered important as an evaluation of QT prolongation in safety pharmacology. In this study, we aimed to clarify the usefulness of rabbit model animals whose knockout of IKs channel responsible for repolarization in the ventricular muscle by genomic editing technique and reduced repolarization reserve power. Several mutant individuals were obtained in genome editing. For these animals, we examined the effect of IKr channel blocker E-4031 under anesthesia and on the QT interval in the electrocardiogram, but no significant prolongation could be observed.