Table 2.

Advantages and disadvantages of saRNA-based vaccines.

Property	Advantage	Disadvantage
Efficacy	Comparable efficacy to traditional protein-based vaccines	Prime/boost administrations may be required
	High level of RNA amplification in situ	Little information is available on the effects of sustained, high-level amplification and expression of saRNAs
	saRNA activity occurs in the cytoplasm so nuclear import is not required as for DNA vaccines
	Humoral and cellular responses are elicited against the expressed antigen
	Protection against infection has been demonstrated in preclinical studies
Safety	Viral genes for structural proteins are removed from the saRNA replicon to prevent viral assembly	Little information is available regarding immunogenicity of the RdRP complex
	Cytoplasmic mode of action, no danger of integration	Limited clinical data to date
Synthesis	Amenable to large-scale synthesis using GMP in vitro transcription
	New sequences for different antigens can be synthesized easily
	Flexibility to incorporate polyvalent or multipathogen sequences
Delivery by NVVs	Can be delivered using nonviral vectors	Delivery is not typically tissue-specific
	Formulations are amenable to large-scale synthesis	Balancing immunogenicity of NVVs and saRNA
	Expression at delivery site following intramuscular, intradermal, or subcutaneous injection