Fig. 4

Various delivery methods and carrier molecules for mRNA vaccines, along with the typical diameters of the particulate complexes: a Naked mRNA: mRNA without any carrier or delivery system. b) Naked mRNA with in vivo electroporation: mRNA is introduced into cells by applying an electric field to facilitate uptake. c Protamine-complexed mRNA: mRNA is complexed with protamine, a cationic peptide, to improve stability and cellular uptake. d mRNA in cationic nanoemulsion: mRNA is associated with a positively charged oil-in-water cationic nanoemulsion to enhance delivery. e mRNA with dendrimer and PEG-lipid: mRNA is associated with a chemically modified dendrimer and complexed with polyethylene glycol (PEG)-lipid for improved delivery and reduced immunogenicity. f Protamine-complexed mRNA in a PEG-lipid nanoparticle: mRNA is complexed with protamine and encapsulated in a PEG-lipid nanoparticle for enhanced stability and delivery. g mRNA with polyethylenimine (PEI): mRNA is associated with a cationic polymer like PEI to improve delivery and transfection efficiency. h mRNA with PEI and lipid component: mRNA is associated with PEI and a lipid component for improved delivery and reduced immunogenicity. i mRNA in a polysaccharide particle or gel: mRNA is associated with a polysaccharide, such as chitosan, to form a particle or gel for improved stability and delivery. j mRNA in cationic lipid nanoparticle: mRNA is encapsulated in a cationic lipid nanoparticle (e.g., DOTAP or DOPE lipids) for enhanced stability and cellular uptake. k mRNA complexed with cationic lipids and cholesterol: mRNA is complexed with cationic lipids and cholesterol for improved stability and delivery. l mRNA complexed with cationic lipids, cholesterol, and PEG-lipid: mRNA is complexed with cationic lipids, cholesterol, and PEG-lipid for enhanced stability, delivery, and reduced immunogenicity. Reprinted from [126] with permission from Springer Nature