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. 2022 May 3;13:884862. doi: 10.3389/fimmu.2022.884862

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Copyright © 2022 Jawalagatti, Kirthika and Lee

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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History and design of mRNA vaccines. (A) Timeline depicting some of the key milestones that contributed to the first successful mRNA vaccines developed against COVID-19. The timeline was adapted from Sahin et al., 2014 (ref. 27) Hou et al., 2021 (28); and Dolgin, 2021 (29). (B) The DNA-launched-mRNA vaccine design for bacterial delivery. pSFV3-lacZ, an SFV replicon-based vector, was used after making several modifications. 1- The ampicillin resistance marker was replaced with asd, an auxotrophic marker to enable antibiotic-free maintenance and delivery of the vector. 2- The SP6 promoter was replaced with the cytomegalovirus (CMV) promoter. 3- The SV40 promoter was placed just before the SFV sub-genomic core promoter to enable direct nuclear transcription of the vaccine constructs. 4- lacZ was replaced with multiple cloning site (MCS) sequences. nsp 1-4 from SFV constitute the replicon, which drives efficient transgene expression through RdRp. pA, polyadenylation signal; Ori, pBR origin of replication; RdRp, RNA dependent RNA polymerase; nsp, non-structural protein; SFV, Semliki Forest virus.