Artificial intelligence-driven rational design of ionizable lipids for mRNA delivery

Lipid nanoparticles (LNPs) have proven effective in mRNA delivery, as evidenced by COVID-19 vaccines. Its key ingredient, ionizable lipids, is traditionally optimized by inefficient and costly experimental screening. This study leverages artificial intelligence (AI) and virtual screening to facilitate the rational design of ionizable lipids by predicting two key properties of LNPs, apparent pKa and mRNA delivery efficiency. Nearly 20 million ionizable lipids were evaluated through two iterations of AI-driven generation and screening, yielding three and six new molecules, respectively. In mouse test validation, one lipid from the initial iteration, featuring a benzene ring, demonstrated performance comparable…

• NN
  National Natural Science Foundation of China

  Award: 32301174
• UD
  Universidade de Macau

  Awards: MYRG-CRG2022-00008-ICMS, 0071/2024/RIA1, ICMS/RTO/EP160/2023
• FP
  Fundo para o Desenvolvimento das Ciências e da Tecnologia

  Awards: 005/2023/SKL, 0071/2024/RIA1
• ST
  Science, Technology and Innovation Commission of Shenzhen Municipality

  Award: SGDX20210823103802016