. 2023 Sep 11;8:341. doi: 10.1038/s41392-023-01561-x

Table 1.

Comparison of mRNA vaccine and circRNA vaccine

	mRNA vaccine	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