Material Design for Next-Generation mRNA Vaccines Using Lipid Nanoparticles

mRNA therapeutics for disease therapy: principles, delivery, and clinical translation

“…In addition to many saRNA vaccines in clinical development, Arcturus Therapeutics has developed the most advanced self-amplifying RNA vaccine, ARCT-154, which opened a Phase 1 clinical trial in the summer of 2020 and is currently in Phase 3 clinical trial. 71 This Phase 3 clinical trial, during which Vietnam transitioned from the Delta mutant strain to the Omicron mutant strain was confirmed, showed that the self-amplified RNA COVID-19 vaccine provided 55% protection against symptomatic COVID-19 pneumonia and 95.3% protection against severe disease and death. There were 9 COVID-19-related deaths in the control group and only 1 in the experimental group, an COVID-19 severe illnesses in the control group, and only 2 COVID-19 severe illnesses in the experimental group.…”

Next-generation materials for RNA–lipid nanoparticles: lyophilization and targeted transfection

“…1). 2,8–20 The ionizable lipid SM-102 (Lipid H) is utilized in the mRNA-1273 (Spikevax) vaccine, and the ionizable lipid ALC-0315 is used in the BNT162b2 (Comirnaty) vaccine (Fig. 1).…”

“…As an alternative to DNA therapy using plasmid DNA, RNA functions in the cellular cytosol, preventing the possible risks of insertion into patient genomes. 1,2 RNA drugs can be developed very quickly in response to new unknown diseases, including biohazards from bioweapons or unknown viruses. Only mRNA vaccines were approved in the USA, Japan and European countries in December 2020, when coronavirus disease 2019 (COVID-19) spread worldwide in late 2019.…”

“…Only mRNA vaccines were approved in the USA, Japan and European countries in December 2020, when coronavirus disease 2019 (COVID-19) spread worldwide in late 2019. 2–4 However, RNA drugs, including mRNA vaccines, need carriers for delivery into the patient body. Several delivery carriers of mRNA, such as cationic polymers, lipoplexes, lipid–polymer nanoparticles and lipid nanoparticles (LNPs), have been investigated.…”

“…The cold chain problem of mRNA-LNP vaccines generates a critical obstacle to vaccine delivery in developing countries with poor infrastructure. 2 Most research on mRNA-LNPs, miRNA-LNPs or siRNA-LNPs has been devoted to pursuing highly efficient RNA expression in vitro and in vivo . 8–22 Only a few studies have investigated the long-term storage of RNA-LNPs.…”