Development of siRNA delivery for hematological malignancy using exosomal lipid

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16197
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Toda Yuki 京都薬科大学, 薬学部, 助教 (40779724)
• Research Collaborator: Ashihara Eishi ; Morita Shin-ya
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: エクソソーム / siRNA / 血液がん / リポソーム

Outline of Final Research Achievements

Gene therapy using siRNA is one of the most promising strategy makes cancer therapy more effective and safer. However, development of delivery technology is essential for siRNA therapeutics which is easily degraded by nuclease in body. Notably, the incorporation of siRNA into blood cancer cells has not been achieved. In this study, we prompted to introduce siRNA into some types of blood cancer cells (multiple myeloma and acute myeloid leukemia) using their own extracellular vesicles (exosomes). Encapsulation of siRNA into exosomes promoted their internalization into cells, while it was not enough amount to induce RNA interference. Enhancement of the efficacy of exosome incorporation into cells and siRNA loading into exosomes could be required to solve this problem.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

狙った分子へ特異的に作用するsiRNA製剤は、現在使用されているがん治療薬よりも安全性が極めて高いと言われている。siRNAは細胞内に移行することで作用を発揮するが、血液がん細胞に対してsiRNAを細胞内導入する技術は未だ開発されていない。本研究では、血液がん細胞株が分泌する顆粒（エクソソーム）にsiRNAを包み込ませることにより、分泌元の血液がん細胞内に送達させることに成功した。本成果は、血液がんに対するsiRNA製剤の開発に繋がる重要な知見である。