Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

Tian Zhang; Han Yin; Yu Li; Haiyin Yang; Kun Ge; Jinchao Zhang; Qing Yuan; Xuyan Dai; Abid Naeem; Yuhua Weng; Yuanyu Huang; Xing-Jie Liang

doi:10.1016/j.isci.2024.109804

Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

iScience. 2024 Apr 23;27(6):109804. doi: 10.1016/j.isci.2024.109804. eCollection 2024 Jun 21.

Authors

Tian Zhang¹, Han Yin¹, Yu Li¹, Haiyin Yang¹, Kun Ge², Jinchao Zhang², Qing Yuan³, Xuyan Dai⁴, Abid Naeem¹, Yuhua Weng¹, Yuanyu Huang¹, Xing-Jie Liang^{5

6}

Affiliations

¹ Advanced Research Institute of Multidisciplinary Science, School of Life Science, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing 100081, China.
² Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002 China.
³ Department of Chemistry, Faculty of Environment and Life Science, Center of Excellence for Environmental Safety and Biological Effects, Beijing University of Technology, Beijing 100124, China.
⁴ Apharige Therapeutics Co., Ltd, Beijing 102629, China.
⁵ Chinese Academy of Sciences (CAS), Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
⁶ University of Chinese Academy of Sciences, Beijing 100049, P.R. China.

Abstract

Nucleic acid therapeutics offer tremendous promise for addressing a wide range of common public health conditions. However, the in vivo nucleic acids delivery faces significant biological challenges. Lipid nanoparticles (LNPs) possess several advantages, such as simple preparation, high stability, efficient cellular uptake, endosome escape capabilities, etc., making them suitable for delivery vectors. However, the extensive hepatic accumulation of LNPs poses a challenge for successful development of LNPs-based nucleic acid therapeutics for extrahepatic diseases. To overcome this hurdle, researchers have been focusing on modifying the surface properties of LNPs to achieve precise delivery. The review aims to provide current insights into strategies for LNPs-based organ-selective nucleic acid delivery. In addition, it delves into the general design principles, targeting mechanisms, and clinical development of organ-selective LNPs. In conclusion, this review provides a comprehensive overview to provide guidance and valuable insights for further research and development of organ-selective nucleic acid delivery systems.

Keywords: Drug delivery system; Nanoparticles; Nucleic acids.

Publication types

Review