Categories of mRNA Constructs

Two forms of mRNA vaccines have been developed according to mRNA constructs, including conventional mRNA vaccine and self-amplifying mRNA vaccine. Conventional mRNA vaccines, also known as non-replicating mRNA vaccines, drive transient antigen expressions after transfection. Self-amplifying mRNA is based on the genome of positive-stranded RNA viruses, encoding both the antigen and the viral replication machinery that are able to direct intracellular RNA amplification.

Fig.1 Two categories of mRNA constructs are being actively evaluated. (Jackson, N. A., et al, 2020)

According to mRNA constructs, two categories of mRNA vaccines are

• Conventional mRNA vaccines

The mRNA contains an ORF for encoding the antigen of interest, flanked by untranslated regions (5' and 3' UTRs) and with a terminal 5' cap and poly(A) tail structure. The vaccines drive transient antigen expressions after transfection. In addition, according to different delivery methods, the non-replicating mRNA vaccines can be further distinguished as dendritic cell mRNA vaccines and direct injection of non-replicating mRNA vaccines.

• Self-amplify mRNA vaccines

Non-replicating mRNA has a 5' cap structure, untranslated regions (5' and 3' UTRs), an open-reading frame (ORF), and a 3' poly(A) tail, the same as self-amplifying mRNA. There is a distinction between the two mRNAs since self-amplifying mRNA, since self-amplifying mRNA has the inclusion of genetic replication machinery derived from positive-stranded mRNA viruses.