Lipid nanoparticles for mRNA delivery

Abstract

Messenger RNA (mRNA) has emerged as a new category of therapeutic agent to prevent and treat various diseases. To function in vivo, mRNA requires safe, effective and stable delivery systems that protect the nucleic acid from degradation and that allow cellular uptake and mRNA release. Lipid nanoparticles have successfully entered the clinic for the delivery of mRNA; in particular, lipid nanoparticle–mRNA vaccines are now in clinical use against coronavirus disease 2019 (COVID-19), which marks a milestone for mRNA therapeutics. In this Review, we discuss the design of lipid nanoparticles for mRNA delivery and examine physiological barriers and possible administration routes for lipid nanoparticle–mRNA systems. We then consider key points for the clinical translation of lipid nanoparticle–mRNA formulations, including good manufacturing practice, stability, storage and safety, and highlight preclinical and clinical studies of lipid nanoparticle–mRNA therapeutics for infectious diseases, cancer and genetic disorders. Finally, we give an outlook to future possibilities and remaining challenges for this promising technology.

A Review on Current COVID-19 Vaccines and Evaluation of Particulate Vaccine Delivery Systems

“…These take advantage of ionizable lipid nanoparticles to deliver nucleoside-modified mRNA which has the full-length spike protein of SARS-CoV-2. These vaccines were effective, and other vaccines are currently in clinical trials [24]. As vaccine platforms, mRNA molecules are safer and more potent than the other options.…”

Lipid Nanoparticle Technology for Delivering Biologically Active Fatty Acids and Monoglycerides

“…To address these issues, there h been extensive attention placed on developing lipid nanoparticle technologies to enca sulate biologically active fatty acids and monoglycerides and there are several compelli reasons to do so: (1) stable supramolecular structures enable biological functionality fatty acids and monoglycerides along with improving dispersibility; (2) nanoscale size ideal for interfacing with biological targets such as bacterial cells and virus particles; a (3) additionally, nanoscale size enables the potential for cellular uptake, which could le to fatty acids and monoglycerides exhibiting both intracellular and extracellular activiti Moreover, lipid nanoparticles are the most common class of FDA-and EMA-a proved nanomedicines [20], representing a technological platform that offers an asso ment of modifiable features such as size, shape, charge, surface properties (including l and presentation), and responsiveness that can be engineered to increase cargo loadi capacity, chemical stability, and capability to cross various biological barriers dependi on the application context. The fundamental concepts, mechanisms, and emerging stra gies used in nanoparticle development to overcome biological barriers on the system local, and cellular levels have been recently reviewed elsewhere [21][22][23][24][25][26].…”

“…Moreover, lipid nanoparticles are the most common class of FDA- and EMA-approved nanomedicines [ 20 ], representing a technological platform that offers an assortment of modifiable features such as size, shape, charge, surface properties (including ligand presentation), and responsiveness that can be engineered to increase cargo loading capacity, chemical stability, and capability to cross various biological barriers depending on the application context. The fundamental concepts, mechanisms, and emerging strategies used in nanoparticle development to overcome biological barriers on the systemic, local, and cellular levels have been recently reviewed elsewhere [ 21 , 22 , 23 , 24 , 25 , 26 ].…”

Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2

“…APCs then migrate to the lymph node nearest to the vaccination site (Figure 2). Passive drainage of mRNA-LNPs through lymphatic vessels allows for direct delivery of mRNA to the lymph nodes containing resident APCs within them, e.g., subcapsular sinus macrophages [62] (Figure 3).…”

“…APCs then migrate to the lymph node nearest to the vaccination site (Figure 2). Passive drainage of mRNA-LNPs through lymphatic vessels allows for direct delivery of mRNA to the lymph nodes containing resident APCs within them, e.g., subcapsular sinus macrophages [62] (Figure 3). Thanks to its lipid structure, endocytosis of LNPs occurs and the mRNA is released into the host cell cytosol, where mRNA combines with ribosomes and begins to be translated to form metastable trimeric prefusion S protein.…”