2023-06-28 カーディフ大学
◆この研究により、機械学習と人工知能がより効果的なナノ治療薬の設計において重要な役割を果たすことが示され、数千種類のナノ粒子の分析と設計、多様な疾患への治療薬の送達が可能となる可能性があります。この新しい手法は、ナノ粒子の開発を迅速化することができるため、医療分野において大きな進展が期待されています。
<関連情報>
- https://www.cardiff.ac.uk/news/view/2728830-ai-generated-nanoparticles-prove-capable-of-delivering-modern-medicines-to-diseased-cells
- https://onlinelibrary.wiley.com/doi/10.1002/smtd.202201695
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
DOI:https://doi.org/10.1002/smtd.202201695
Abstract
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.
