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Nano–Bio Interactions: Exploring the Biological Behavior and the Fate of Lipid-Based Gene Delivery Systems

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Abstract

Gene therapy for many diseases is rapidly becoming a reality, as demonstrated by the recent approval of various nucleic acid-based therapeutics. Non-viral systems such as lipid-based carriers, lipid nanoparticles (LNPs), for delivering different payloads including small interfering RNA, plasmid DNA, and messenger RNA have been particularly extensively explored and developed for clinical uses. One of the most important issues in LNP development is delivery to extrahepatic tissues. To achieve this, various lipids and lipid-like materials are being examined and screened. Several LNP formulations that target extrahepatic tissues, such as the spleen and the lungs have been developed by adjusting the lipid compositions of LNPs. However, mechanistic details of how the characteristics of LNPs affect delivery efficiency remains unclear. The purpose of this review is to provide an overview of LNP-based nucleic acid delivery focusing on LNP components and their structures, as well as discussing biological factors, such as biomolecular corona and cellular responses related to the delivery efficiency.

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Acknowledgements

We wish to thank Dr. Milton Feather for his helpful advice in editing this manuscript.

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Authors and Affiliations

  1. Integrated Research Consortium on Chemical Sciences, Graduate School of Science, Nagoya University, Nagoya, 464-8602, Japan

    Seigo Kimura

  2. Laboratory for Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan

    Hideyoshi Harashima

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  1. Seigo Kimura
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Correspondence to Seigo Kimura or Hideyoshi Harashima.

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Kimura, S., Harashima, H. Nano–Bio Interactions: Exploring the Biological Behavior and the Fate of Lipid-Based Gene Delivery Systems. BioDrugs 38, 259–273 (2024). https://doi.org/10.1007/s40259-024-00647-4

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