4.8 Review

Lipids and Lipid Derivatives for RNA Delivery

Journal

CHEMICAL REVIEWS
Volume 121, Issue 20, Pages 12181-12277

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrev.1c00244

Keywords

-

Funding

  1. National PKU Alliance
  2. AAPS Foundation
  3. National Institute of General Medical Sciences [R35GM119679]
  4. National Heart, Lung, and Blood Institute [R01HL136652]
  5. College of Pharmacy at The Ohio State University
  6. Early Career Investigator Award from the Bayer Hemophilia Awards Program

Ask authors/readers for more resources

RNA-based therapeutics have shown great promise in treating diseases through various mechanisms, with lipid nanoparticles being the most widely used delivery system. The study of lipids, lipid derivatives, and lipid-derived macromolecules for RNA delivery has also made significant progress in recent years.
RNA-based therapeutics have shown great promise in treating a broad spectrum of diseases through various mechanisms including knockdown of pathological genes, expression of therapeutic proteins, and programmed gene editing. Due to the inherent instability and negative-charges of RNA molecules, RNA-based therapeutics can make the most use of delivery systems to overcome biological barriers and to release the RNA payload into the cytosol. Among different types of delivery systems, lipid-based RNA delivery systems, particularly lipid nanoparticles (LNPs), have been extensively studied due to their unique properties, such as simple chemical synthesis of lipid components, scalable manufacturing processes of LNPs, and wide packaging capability. LNPs represent the most widely used delivery systems for RNA-based therapeutics, as evidenced by the clinical approvals of three LNP-RNA formulations, patisiran, BNT162b2, and mRNA-1273. This review covers recent advances of lipids, lipid derivatives, and lipid-derived macromolecules used in RNA delivery over the past several decades. We focus mainly on their chemical structures, synthetic routes, characterization, formulation methods, and structure-activity relationships. We also briefly describe the current status of representative preclinical studies and clinical trials and highlight future opportunities and challenges.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available