AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery.

Journal: Nature communications
PMID: 39060305

Abstract

Ionizable lipid nanoparticles (LNPs) are seeing widespread use in mRNA delivery, notably in SARS-CoV-2 mRNA vaccines. However, the expansion of mRNA therapies beyond COVID-19 is impeded by the absence of LNPs tailored for diverse cell types. In this study, we present the AI-Guided Ionizable Lipid Engineering (AGILE) platform, a synergistic combination of deep learning and combinatorial chemistry. AGILE streamlines ionizable lipid development with efficient library design, in silico lipid screening via deep neural networks, and adaptability to diverse cell lines. Using AGILE, we rapidly design, synthesize, and evaluate ionizable lipids for mRNA delivery, selecting from a vast library. Intriguingly, AGILE reveals cell-specific preferences for ionizable lipids, indicating tailoring for optimal delivery to varying cell types. These highlight AGILE's potential in expediting the development of customized LNPs, addressing the complex needs of mRNA delivery in clinical practice, thereby broadening the scope and efficacy of mRNA therapies.

Authors

  • Yue Xu
  • Shihao Ma
    Department of Computer Science, University of Toronto, Toronto, ON, Canada.
  • Haotian Cui
    Peter Munk Cardiac Center, University Health Network, Toronto, Ontario, Canada.
  • Jingan Chen
    Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
  • Shufen Xu
    Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
  • Fanglin Gong
    Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
  • Alex Golubovic
    Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
  • Muye Zhou
    Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
  • Kevin Chang Wang
    Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
  • Andrew Varley
    Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
  • Rick Xing Ze Lu
    Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
  • Bo Wang
    Department of Clinical Laboratory Medicine Center, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China.
  • Bowen Li
    Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, China.

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