ArticleNPJ vaccines2025
Novel enzymatic DNA produced from a text file achieves comparable immune responses as plasmid vaccine.
Article in NPJ vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
13 authors.
Funding
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.
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Registered trials
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