Development of tissue-cell two-step targeting method using cells producing siRNA-loaded exosomes.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21891
• 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: Kyoto University
• Principal Investigator: Takahashi Yuki 京都大学, 薬学研究科, 准教授 (00547870)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 細胞外小胞 / エキソソーム

Outline of Final Research Achievements

To develop a two-step targeting method at the tissue-cell level using siRNA-loaded exosome-producing cells, we investigated the regulation of cellular dynamics and the development of a method for siRNA loading onto exosomes. We investigated the improvement of inflammation site accumulation by introducing the chemokine receptor CCR2 into cells, and found that it enhanced migration to macrophages, which have inflammation-inducing effects. Next, we examined the improvement of RNA loading efficiency onto exosomes. The loading efficiency could be improved by the fusion protein of exosome migratory protein and RNA-binding protein. On the other hand, complexation of the loaded RNA was not effective. These findings are useful for the development of a two-step targeting method using exosomes.

Free Research Field

生物薬剤学

Academic Significance and Societal Importance of the Research Achievements

本研究ではsiRNA搭載エキソソーム産生細胞を利用した組織―細胞レベルでの二段階ターゲティング法の開発を目的として、細胞の動態の制御とエキソソームへのsiRNA搭載法の開発について検討を行った。siRNAの効率的なデリバリー法の開発は有用な治療法になると考えられるが、二段階ターゲティング法は効果的なsiRNAデリバリー法となりえる。本研究ではそのために必要となる細胞の動態制御法と、エキソソームへのsiRNA搭載法の開発に成功した。