Development of visualized nano-DDS agents targeting brain by RNA aptamers and quantum dots

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19909
• 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 Tokyo
• Principal Investigator: Takahashi Masaki 東京大学, 医科学研究所, 特任准教授 (00549529)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: アプタマー / 薬剤送達 / 脳

Outline of Final Research Achievements

We worked on the generation of aptamer molecules for brain drug delivery (brain DDS) and the establishment of a method for their visual evaluation by employing fluorescent molecular labelling. We consequently succeeded in generating aptamer molecules targeting the transferrin receptors (TfR) and insulin receptors (IR), which are promising targets for the brain-DDS strategy, and then verifying the fluorescent substances (Alexa and quantum dots) to be labelled, they were administered to mice and observed using in vivo imaging equipment. As a result, it was difficult to detect fluorescence in the head in live imaging, but fluorescence could be observed in brain tissue sections, indicating that intended aptamers　could be created and that further work is needed for establishing live imaging technologies.

Free Research Field

核酸創薬科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、安全性や特異性が高い核酸医薬「RNAアプタマー」を用いて、社会的な創薬ニーズの高い薬剤を脳へ送達する分子創製やその評価技術構築に取り組んだ。その中で、残念ながら蛍光物質を活かしたin vivoイメージングは修飾分子合成の課題などで目標を達成することができなかったが、その一方で、創製したアプタマーが脳組織に移行してることを示すデータを得ることができた。従って、薬剤脳送達に必要となる輸送体となるアプタマーが得られており、今後さらなる検証により、創薬領域で需要の高い安全かつ効果的な脳DDS技術の実現に一歩近づけたものと考えている。