Establishment of novel gene therapy preclinical model using Baboon envelope pseudotyped lentiviral vector

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07750
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kanazawa University
• Principal Investigator: Ikawa Yasuhiro 金沢大学, 医学系, 准教授 (10722043)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 遺伝子治療 / Baboonエンベロープ / レンチウイルス / DNA修復障害 / Bloom症候群

Outline of Final Research Achievements

DNA repair disorders show the vulnerability by cytokine stimulations and induces apoptosis. Therefore, the establishment of novel transduction methodology, cytokine depletion method, was warranted. Baboon envelope pseudotyped lentiviral vector (Ba-LV) transduce without cytokine transduction, therefore we planed gene transfer using Ba-LV to Bloom syndrome model mouse (Blm), which is one of the representative DNA repair disorder. However, the efficacy of virus production was very low. Therefore, we succeeded to establish novel Ba-LV production protocol.
Thereafter, we verified vulnerability difference between wild type mouse's bone marrow cells and those of Blm by evaluating sister chromatid exchange. In the future, we would transduce Blm bone marrow cells with Ba-LV for recovering their function.

Free Research Field

遺伝子治療

Academic Significance and Societal Importance of the Research Achievements

本結果は遺伝子治療が難しいと考えられていたDNA修復障害疾患という領域に、新たな可能性を見出すことに施行した。また、サイトカイン刺激は造血幹細胞の分化を進めてしまうことが知られている。そこで、本サイトカイン刺激を省いた新たな遺伝子導入法は、DNA修復障害疾患にかかわらず一般的な造血幹細胞を用いた遺伝子治療においても、より有効な遺伝子治療成績を出すことに寄与すると考えられた。