Development of BBB-penetrating Drug Delivery System against Neurotropic viral infection

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03136
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Nagasaki University
• Principal Investigator: YOSHII Kentaro 長崎大学, 高度感染症研究センター, 教授 (50421988)
• Co-Investigator(Kenkyū-buntansha): 小林 進太郎 北海道大学, 獣医学研究院, 准教授 (00634205) ; 五十嵐 学 北海道大学, 人獣共通感染症国際共同研究所, 准教授 (10374240) ; 今内 覚 北海道大学, 獣医学研究院, 教授 (40396304)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: フラビウイルス / 血液脳関門 / 人獣共通感染症 / 組換え抗体

Outline of Final Research Achievements

The neurotropic zoonotic viral infection causes severe neurological symptoms by invading and replicating in the brain with a high fatality rate. However, due to the presence of the blood-brain barrier (BBB), there has been no method to deliver antiviral molecules to the virus-infected brain to inhibit its replication, and thus no treatment has been developed. This study aimed to develop a transport method for antiviral molecules that target the virus in the brain by using the properties of molecules capable of crossing the BBB. Recombinant antibodies were produced by fusing peptides with BBB-penetrating properties to neutralizing antibodies against the neurotropic virus. When administered to virus-infected mice, an increase in survival rate was observed, demonstrating the potential application of this approach to treatment of neurotropic viral infections.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

神経向性の人獣共通感染症のウイルスは、脳炎などの重篤な症状を引き起こすにもかかわらず、血液脳関門（BBB）の存在により、有効な治療法開発が滞っていた。本研究はBBBを通過する分子の性質を利用した抗ウイルス分子の脳内輸送法の検討と、それを用いて感染モデルでの病態発現への影響を示したものであり、今後の治療法開発における重要な基盤となりうると期待される。