AIが生成したナノ粒子が病気の細胞に最新の医薬品を送達できることを証明(AI-generated nanoparticles prove capable of delivering modern medicines to diseased cells)


2023-06-28 カーディフ大学



細胞内生物学を理解し、脂質ナノ粒子によるmRNA送達を改善する Understanding Intracellular Biology to Improve mRNA Delivery by Lipid Nanoparticles

Morag Rose Hunter, Lili Cui, Benjamin Thomas Porebski, Sara Pereira, Silvia Sonzini, Uchechukwu Odunze, Preeti Iyer, Ola Engkvist, Rebecca Louise Lloyd, Samantha Peel, Alan Sabirsh, Douglas Ross-Thriepland, Arwyn Tomos Jones, Arpan Shailesh Desai
Small Methods  Published: 14 June 2023

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Poor understanding of intracellular delivery and targeting hinders development of nucleic acid-based therapeutics transported by nanoparticles. Utilizing a siRNA-targeting and small molecule profiling approach with advanced imaging and machine learning biological insights is generated into the mechanism of lipid nanoparticle (MC3-LNP) delivery of mRNA. This workflow is termed Advanced Cellular and Endocytic profiling for Intracellular Delivery (ACE-ID). A cell-based imaging assay and perturbation of 178 targets relevant to intracellular trafficking is used to identify corresponding effects on functional mRNA delivery. Targets improving delivery are analyzed by extracting data-rich phenotypic fingerprints from images using advanced image analysis algorithms. Machine learning is used to determine key features correlating with enhanced delivery, identifying fluid-phase endocytosis as a productive cellular entry route. With this new knowledge, MC3-LNP is re-engineered to target macropinocytosis, and this significantly improves mRNA delivery in vitro and in vivo. The ACE-ID approach can be broadly applicable for optimizing nanomedicine-based intracellular delivery systems and has the potential to accelerate the development of delivery systems for nucleic acid-based therapeutics.