Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

Jing Yan; Hao Zhang; Guangfeng Li; Jiacan Su; Yan Wei; Can Xu

doi:10.1016/j.apsb.2023.10.012

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

Acta Pharm Sin B. 2024 Feb;14(2):579-601. doi: 10.1016/j.apsb.2023.10.012. Epub 2023 Oct 20.

Authors

Jing Yan^{1

2}, Hao Zhang^{1

3}, Guangfeng Li⁴, Jiacan Su^{1

3

5}, Yan Wei^{1

5}, Can Xu⁶

Affiliations

¹ Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
² Institute of Medicine, Shanghai University, Shanghai 200444, China.
³ Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
⁴ Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai 200941, China.
⁵ Organoid Research Center, Shanghai University, Shanghai 200444, China.
⁶ Department of Gastroenterology, Changhai Hospital, Shanghai 200433, China.

Abstract

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

Keywords: Barriers to systemic RNA delivery; Extrahepatic tissue targeting; Fabrication methods; Lipid components; Lipid nanovehicle design; Lipid nanovehicles; Organ tropism; RNA therapeutics.

Publication types

Review