The Future of Tissue-Targeted Lipid Nanoparticle-Mediated Nucleic Acid Delivery

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 15; no. 7; p. 897
• Main Authors: Kularatne, Ruvanthi N., Crist, Rachael M., Stern, Stephan T.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20-07-2022; MDPI
• Subjects: Acids; Amyloidosis; Antibodies; Cholesterol; Dendritic cells; drug delivery; Ethanol; FDA approval; Ligands; lipid nanoparticles; Lipids; Liver; Lymphatic system; Medical research; mRNA vaccines; Nanoparticles; Review; Severe acute respiratory syndrome coronavirus 2; Spleen; therapeutic nucleic acids
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph15070897

The earliest example of in vivo expression of exogenous mRNA is by direct intramuscular injection in mice without the aid of a delivery vehicle. The current state of the art for therapeutic nucleic acid delivery is lipid nanoparticles (LNP), which are composed of cholesterol, a helper lipid, a PEGylated lipid and an ionizable amine-containing lipid. The liver is the primary organ of LNP accumulation following intravenous administration and is also observed to varying degrees following intramuscular and subcutaneous routes. Delivery of nucleic acid to hepatocytes by LNP has therapeutic potential, but there are many disease indications that would benefit from non-hepatic LNP tissue and cell population targeting, such as cancer, and neurological, cardiovascular and infectious diseases. This review will concentrate on the current efforts to develop the next generation of tissue-targeted LNP constructs for therapeutic nucleic acids.