Challenges in dual-targeted nose-to-brain micelles for infected neuron-specific RNA delivery

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19921
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: The University of Tokushima (2023); University of Shizuoka (2022)
• Principal Investigator: KANAZAWA Takanori 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (60434015)
• Co-Investigator(Kenkyū-buntansha): 宮田 完二郎 東京大学, 大学院工学系研究科(工学部), 教授 (50436523) ; 中南 秀将 東京薬科大学, 薬学部, 教授 (20548515)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: Nose-to-Brain / ナノ粒子 / RNAデリバリー / ウイルス脳感染

Outline of Final Research Achievements

In this study, based on the nanoparticle technology (Nose-to-Brain micelles, NtB micelles) originally developed by the principal investigator, we established a DDS that can deliver RNA drugs to the olfactory bulb, brain stem, and infected neurons, which are the main sites of viral brain infection. We found that NtB micelles of less than 50 nm, which exhibit a slight positive charge, are suitable for delivery to the olfactory bulb and brainstem. We also established the conditions for ligand modification by click reaction for target-directed delivery of NtB. Furthermore, we succeeded in establishing virus-infected human neurons and demonstrated that NtB micelles are incorporated into these cells. In summary, this study established a nanoparticle technology that can be delivered to the primary site of viral infection and to infected neurons.

Free Research Field

薬物送達学

Academic Significance and Societal Importance of the Research Achievements

本研究を通じて、高度な設備を持つ限られた機関しか取り扱えないSARS-CoV-2感染ヒト細胞を用いた機能検証から得られる知見は社会的重要度の高いものとなることが期待される。さらに、本研究で開発する脳特定部位（嗅球・脳幹部）の標的細胞に選択的かつ高濃度にRNA医薬を届ける技術は、SARS-CoV-2と同様に、有効な治療薬のない深刻な中枢機能障害を生じる様々な脳感染ウイルスや今後出現する新興ウイルス、さらには、認知・運動等を司る脳特定部位で病態が進行する神経変性疾患に対する治療薬開発にも大きな貢献が見込まれるため、その波及効果は計り知れず、学術的かつ社会的意義は大きい。