Development of gene therapy against neurodegenerative diseases using CRISPR/Cas9-based genome editing

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15477
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Gunma University
• Principal Investigator: Hirai Hirokazu 群馬大学, 大学院医学系研究科, 教授 (70291086)
• Co-Investigator(Renkei-kenkyūsha): HOSOI Nobutake 群馬大学, 大学院医学系研究科, 講師 (90543570) ; KONNO Ayumu 群馬大学, 大学院医学系研究科, 講師 (40509048)
• Research Collaborator: MATSUZAKI Yasunori 群馬大学, 大学院医学系研究科, 助教 (50738200)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 小脳 / プルキンエ細胞 / 細胞種特異的プロモーター / CRISPR/Cas9 / ゲノム編集 / AAV / ウイルスベクター

Outline of Final Research Achievements

In this research, we aimed to establish a technique that allows elimination of a disease-causing gene from specific cell populations in the brain, using adeno-associated virus (AAV) vectors in combination with CRISPR/Cas9 system. Initially, we characterized neuron-specific, astrocyte-specific and cerebellar Purkinje cell-specific promoters available for AAV vector-mediated transgene expression. The results were published in 3 papers. Then, using the AAV vectors, we examined whether a gene responsible for developmental defects of the brain could be knocked out from Purkinje cells by CRISPR/Cas9 system. The results showed successful removal of the gene from around two thirds of Purkinje cells.

Free Research Field

神経生理学、神経科学