Table 1 Comparison of mRNA vaccine and circRNA vaccine

Preparation

• Codon optimizations

• UTR optimizations

• Cap and Poly (A) tail design

• Nucleotide modifications

• In vitro transcription (IVT)

• Purification

• Translation optimizations

• Circularization optimizations

• Nucleotide modifications

• IVT

• Circularization

• Purification

Storage

• Refrigeration in ultra-cold and RNase-free and sterile conditions

• Non-cryopreservation and preservation under fewer freezing and thawing cycles^28,30

Biosecurity

• High immunogenicity of unmodified mRNA

• Low immunogenicity of modified mRNA

• Low immunogenicity of unmodified circRNA^27,38

• Lower and even no immunogenicity of modified circRNA⁶⁸

Delivery

• LNP

• Polymetric nanoparticles

• Cationic nanoemulsion

• Exosomes

• Solid lipid nanoparticles nanostructured lipid carriers

• Naked delivery

• Compatible with mRNA delivery options

Antigens encoding

• Low antigen-encoding endurance due to biodegradation of mRNA

• Prolonged antigen coding tolerances due to the high longevity of circRNA^27,29,30,70

Application

• Vaccines, encoding adjuvant, encoding antibody, gene editing, and protein replacement

• Compatible with mRNA application. In addition, circRNA can also be applied to sponges and endogenous circRNA mimics