Lipid nanoparticle (LNP) formulations of messenger RNA (mRNA) have demonstrated high efficacy as vaccines against SARS-CoV-2. The success of these nanoformulations underscores the potential of LNPs as a delivery system for next-generation biological therapies. In this article, we highlight the key considerations necessary for engineering LNPs as a vaccine delivery system and explore areas for further optimisation. There remain opportunities to improve the protection of mRNA, optimise cytosolic delivery, target specific cells, minimise adverse side-effects and control the release of RNA from the particle. The modular nature of LNP formulations and the flexibility of mRNA as a payload provide many pathways to implement these strategies. Innovation in LNP vaccines is likely to accelerate with increased enthusiasm following recent successes; however, any advances will have implications for a broad range of therapeutic applications beyond vaccination such as gene therapy.
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http://dx.doi.org/10.1016/j.cocis.2021.101468 | DOI Listing |
Discov Oncol
January 2025
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1, Youyi Road, Yuzhong District, Chongqing, 400010, China.
Purpose: Nano-drug delivery systems (NDDS) have become a promising alternative and adjunctive strategy for lung cancer (LC) treatment. However, comprehensive bibliometric analyses examining global research efforts on NDDS in LC are scarce. This study aims to fill this gap by identifying key research trends, emerging hotspots, and collaboration networks within the field of NDDS and LC.
View Article and Find Full Text PDFJ Biol Inorg Chem
January 2025
Department of Chemistry and Biochemistry, Miami University, Oxford, OH, USA.
Lipid nanoparticles formed with copolymers are a new and increasingly powerful tool for studying membrane proteins, but the extent to which these systems affect the physical properties of the membrane is not completely understood. This is critical to understanding the caveats of these new systems and screening for structural and functional artifacts that might be caused in the membrane proteins they are used to study. To better understand these potential effects, the fluid properties of dipalmitoylphosphatidylcholine lipid bilayers were examined by electron paramagnetic resonance (EPR) spectroscopy with spin-labeled reporter lipids in either liposomes or incorporated into nanoparticles with the copolymers diisobutylene-maleic acid or styrene maleic acid.
View Article and Find Full Text PDFExpert Opin Drug Deliv
January 2025
Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Macclesfield, UK.
Introduction: mRNA therapeutics were a niche area in drug development before COVIDvaccines. Now they are used in vaccine development, for non-viral therapeuticgenome editing, chimericantigen receptor T (CAR T) celltherapies and protein replacement. mRNAis large, charged, and easily degraded by nucleases.
View Article and Find Full Text PDFMol Ther
January 2025
Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, MA, USA, 02139; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; Cambridge, MA, USA, 02139; Department of Chemical Engineering, Massachusetts Institute of Technology; Cambridge, MA, USA, 02139; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University; Cambridge, MA, USA, 02139; Howard Hughes Medical Institute; Chevy Chase, MD, USA, 20815; Department of Materials Science of Engineering; Massachusetts Institute of Technology; Cambridge, MA, USA, 02139. Electronic address:
mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following i.
View Article and Find Full Text PDFNutrients
December 2024
Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA.
Pancreatic ductal adenocarcinoma (PDAC) is one of the worst solid malignancies in regard to outcomes and metabolic dysfunction leading to cachexia. It is alarming that PDAC incidence rates continue to increase and warrant the need for innovative approaches to combat this disease. Due to its relatively slow progression (10-20 years), prevention strategies represent an effective means to improve outcomes.
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