Critical Review of Achs et al. (2025) on Residual DNA in mRNA Vaccine Preparations

In a preprint, Achs et al. (2025) present an analysis from the Biomedical Research Center of the Slovak Academy of Sciences (BMC SAS) of residual plasmid DNA in vials of Pfizer-BioNTech and Moderna modified mRNA vaccines.They conclude that residual DNA present in the drug product is short, highly degraded and biologically irrelevant. Upon technical review, this critique contends that their conclusions are not only premature but also fundamentally unsupported by the approach employed. Methodological omissions—particularly in relation to extraction efficiency, inhibition testing, and sequencing bias—undermine quantitative accuracy. Crucially, their reliance on short-read Illumina sequencing inherently limits the detection of longer, potentially intact DNA fragments. This limitation has been directly addressed by long-read sequencing (Speicher et al., 2025), demonstrating plasmid fragments that exceed 3 kb in length—a finding that Achs et al. were not equipped to observe. This highlights the urgent need for unbiased, multi-platform characterization to reveal the true profile and amount of residual DNA. Additionally, in the light of significant public health implications, full transparency regarding all institutional funding, including from mRNA vaccine manufacturers, including Sensible Biotechnologies Inc., is essential for assessing potential conflicts-of-interest.