Development of ligand modification onto the nanoparticle via click reaction and systematic evaluation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K20195
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Tohoku University (2021); Chiba University (2020)
• Principal Investigator: Sakurai Yu 東北大学, 薬学研究科, 講師 (00707234)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: siRNA / 脂質ナノ粒子 / 核酸 / リガンド修飾 / 抗体 / リンパ

Outline of Final Research Achievements

The thermodynamic instability of nucleic acid-loaded lipid nanoparticles has made it difficult to modify LNPs with ligand molecules to target specific cells. In this study, to solve this problem, I developed a technique for rapid and highly efficient modification methodology for antibodies conjugation using click reactions on the nanoparticle surface. In addition, by developing a systematic optimization, I developed a method that allows to rapidly find the optimal lipid composition and conditions for antibody modification to deliver nucleic acids to target cells. Using these fundamental technologies, I have developed a technology to deliver siRNA to subcutaneous lymphatic endothelial cells and control gene expression using antibody-modified LNPs.

Free Research Field

ドラッグデリバリーシステム

Academic Significance and Societal Importance of the Research Achievements

脂質ナノ粒子（LNP）型核酸医薬は、近年のCOVID-19ワクチンで示されたように非常に強力な治療モダリティである。しかしながら、現在開発が進行中のLNP製剤はほとんどが肝細胞を標的としたものか局所投与によるものが殆どであり、対象となる疾患は限定的である。本研究により開発した抗体修飾技術により、肝細胞以外の細胞へとLNP型核酸医薬の対象を拡充することが可能となり、核酸医薬のさらなる発展に貢献しうる。