Development of rAAV-mediated brain transduction with transient ultrasound-mediated modulation of the blood-brain interface in adult common marmoset toward modeling epilepsy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430102
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Nippon Medical School
• Principal Investigator: Okada Hironori 日本医科大学, 大学院医学研究科, 研究員 (80416271)
• Co-Investigator(Renkei-kenkyūsha): OKADA Takashi 日本医科大学, 大学院医学研究科, 大学院教授 (00326828)
• Research Collaborator: TAKEDA Shinichi 国立精神・神経医療研究センター, 神経研究所, 所長 (90171644) ; KINOH Hiromi 日本医科大学, 医学部, 助教 (60532728) ; KASAHARA Yuko 日本医科大学, 大学院医学研究科, 助教 (90391911)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: AAVベクター / てんかん / マーモセット / 超音波 / 血液脳関門 / 疾患モデル / 成体

Outline of Final Research Achievements

The common marmoset could provide an appropriate model for neuromuscular diseases because of its higher brain function and physiological resemblance to human. An adeno-associated virus (AAV) vector has great advantages to induce pathology in the aged animals. However, fully maturated blood-brain barrier (BBB) significantly limits passive rAAV transport from circulation to the brain. We investigated microbubble(MB)-assisted transcranial ultrasound irradiation (TCUI) BBB opening technology in the adult marmoset. TCUI immediately after bolus injection of MB resulted in the BBB opening in blood vessels in some areas including the hippocampus, and it seemed to be repaired by at least 2 days after TCUI. In parallel, we constructed self-complementary AAV2 vector proviral plasmids expressing dominant negative mutants of sodium ion channel genes (SCN1A or SCN2A), which causes Dravet syndrome. The vector genomes could be packaged into the AAV9 capsid and purified by conventional method.

Free Research Field

実験動物