{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Fuller J"],"funding":["Defense Advanced Research Projects Agency","Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense","NIAID NIH HHS","National Cancer Institute","NCI NIH HHS","NIH/NIAID Collaborative Influenza Vaccine Innovation Centers"],"pagination":["9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12800232"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_abstract":["DNA vaccines have garnered considerable attention due to their recent success in humans for SARS-CoV-2 and immunotherapy for cancer. However, conventional methods for creating and manufacturing DNA vaccines at-scale are slow and rate-limiting for timely response. Herein, we introduce a rapid and completely synthetic workflow that harnesses enzymes to create bulk DNA from a sequence text file. This synthetic workflow termed Enzymatic DNA Synthesis & Rolling-Circle Amplification (EDS-RCA) leverages multiple enzymes to print DNA oligos and assemble them into genes prior to cloning into circular constructs for rolling-circle amplification (RCA). We show that the resulting EDS-RCA DNA elicits comparable vaccine immunogenicity as standard plasmid format, despite the DNA being a large concatemeric repeat. The EDS-RCA method generated the hemagglutinin gene of H1N1 at a mean per-base error rate as low as ~1 mutation every 10,000 bases and, upon DNA vaccination, elicited strong antibody and cellular immune responses. Skin delivery of EDS-DNA using gene gun facilitated striking vaccine dose-sparing capabilities in comparison to intramuscular electroporation methods. In total, DNA vaccines produced by EDS-RCA are immunogenic and amenable to numerous delivery-modalities with preclinical mouse models and could offer an alternative for rapid scale-up of DNA vaccines for future human use."],"journal":["NPJ vaccines"],"pubmed_title":["Novel enzymatic DNA produced from a text file achieves comparable immune responses as plasmid vaccine."],"pmcid":["PMC12800232"],"funding_grant_id":["75N93019C00051","N66001-21-C-4014","T32CA009171","T32 CA009171","HR0011-21-9-0001"],"pubmed_authors":["Weiner DB","Ryan R","Nelson J","Fuller DH","Godron X","Kvam E","Creton S","Griffin W","Hall C","Tursi NJ","Fuller J","Timp W","Blatney K"],"additional_accession":[]},"is_claimable":false,"name":"Novel enzymatic DNA produced from a text file achieves comparable immune responses as plasmid vaccine.","description":"DNA vaccines have garnered considerable attention due to their recent success in humans for SARS-CoV-2 and immunotherapy for cancer. However, conventional methods for creating and manufacturing DNA vaccines at-scale are slow and rate-limiting for timely response. Herein, we introduce a rapid and completely synthetic workflow that harnesses enzymes to create bulk DNA from a sequence text file. This synthetic workflow termed Enzymatic DNA Synthesis & Rolling-Circle Amplification (EDS-RCA) leverages multiple enzymes to print DNA oligos and assemble them into genes prior to cloning into circular constructs for rolling-circle amplification (RCA). We show that the resulting EDS-RCA DNA elicits comparable vaccine immunogenicity as standard plasmid format, despite the DNA being a large concatemeric repeat. The EDS-RCA method generated the hemagglutinin gene of H1N1 at a mean per-base error rate as low as ~1 mutation every 10,000 bases and, upon DNA vaccination, elicited strong antibody and cellular immune responses. Skin delivery of EDS-DNA using gene gun facilitated striking vaccine dose-sparing capabilities in comparison to intramuscular electroporation methods. In total, DNA vaccines produced by EDS-RCA are immunogenic and amenable to numerous delivery-modalities with preclinical mouse models and could offer an alternative for rapid scale-up of DNA vaccines for future human use.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-11T04:59:16.775Z","creation":"2026-06-11T03:08:27.651Z"},"accession":"S-EPMC12800232","cross_references":{"pubmed":["41390774"],"doi":["10.1038/s41541-025-01329-0"]}}