Rational Design of Lipid Nanoparticles for Enhanced mRNA Vaccine Delivery via Machine Learning.

Journal: Small (Weinheim an der Bergstrasse, Germany)
PMID: 39264000

Abstract

Since the coronavirus pandemic, mRNA vaccines have revolutionized the field of vaccinology. Lipid nanoparticles (LNPs) are proposed to enhance mRNA delivery efficiency; however, their design is suboptimal. Here, a rational method for designing LNPs is explored, focusing on the ionizable lipid composition and structural optimization using machine learning (ML) techniques. A total of 213 LNPs are analyzed using random forest regression models trained with 314 features to predict the mRNA expression efficiency. The models, which predict mRNA expression levels post-administration of intradermal injection in mice, identify phenol as the dominant substructure affecting mRNA encapsulation and expression. The specific phospholipids used as components of the LNPs, as well as the N/P ratio and mass ratio, are found to affect the efficacy of mRNA delivery. Structural analysis highlights the impact of the carbon chain length on the encapsulation efficiency and LNP stability. This integrated approach offers a framework for designing advanced LNPs and has the potential to unlock the full potential of mRNA therapeutics.

Authors

  • Seo-Hyeon Bae
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Hosam Choi
    Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Jisun Lee
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Min-Ho Kang
    Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Seong-Ho Ahn
    Department of Artificial Intelligence, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Yu-Sun Lee
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Huijeong Choi
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Sohee Jo
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Yeeun Lee
    Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon 21999, Korea.
  • Hyo-Jung Park
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Seonghyun Lee
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Subin Yoon
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Gahyun Roh
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Seongje Cho
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Youngran Cho
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Dahyeon Ha
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Soo-Yeon Lee
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Eun-Jin Choi
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Ayoung Oh
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Jungmin Kim
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Sowon Lee
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Jungmin Hong
    Department of Chemistry, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Nakyung Lee
    Department of Chemistry, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Minyoung Lee
    Department of Nursing, Inha University, Incheon, South Korea; Graduate School, Inha University, Incheon, South Korea.
  • Jungwon Park
    School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea.
  • Dong-Hwa Jeong
    Department of Artificial Intelligence, The Catholic University of Korea, Bucheon, Republic of Korea.
  • Kiyoun Lee
    Department of Chemistry, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Jae-Hwan Nam
    Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.

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