Misinformation regarding residual DNA in mRNA vaccine products

Misinformation regarding residual DNA in mRNA vaccine products Takeshi Nitta1, Taku Kashiyama2, Yoshihisa Matsumoto3, Tetsuya Toyoda4, Takayuki Miyazawa5, Yukari Kamijima6, Hideki Kakeya7 1 Division of Molecular Pathology, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan 2 Department of Pharmacology, Juntendo University School of Medicine, Tokyo, Japan 3 Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan 4 Choju Medical Institute, Fukushimura Hospital, Aichi, Japan 5 Kyoto Animal Human Organism Research Institute, Kyoto, Japan 6 Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan 7 Institute of Systems and Information Engineering, University of Tsukuba, Tsukuba, Japan Since the report by McKernan et al. in 2023 [1], concerns have been raised that mRNA vaccines are “contaminated” with large amounts of DNA sufficient to cause health damage. During the production process of mRNA vaccines, fragments of the template DNA remain in the final mRNA product as residual DNA. Consequently, regulatory agencies such as the European Medicines Agency (EMA) stipulate that residual DNA in mRNA vaccine products should be less than 10 ng per dose. McKernan and subsequent researchers have claimed that many mRNA vaccines contain DNA levels hundreds of times higher than the regulatory limit [2]. If mRNA products contain residual DNA exceeding the regulatory limit, they are simply defective products and must be recalled without question. McKernan and many other researchers have committed the fundamental error of measuring small amounts of DNA using fluorochromes that bind to DNA molecules without first removing large amounts of RNA present in mRNA vaccines, thereby overestimating residual DNA levels. Regarding this point, researchers from the Slovak Academy of Sciences recently published results measuring DNA levels in mRNA vaccines using multiple appropriate methods, confirming that mRNA vaccines do not contain DNA exceeding regulatory limits [3]. Their measurements are valid and thorough, and their conclusions are reasonable. There is no value in calculating overestimated measurements using methods not validated by regulatory authorities and equipment/reagent manufacturers. What about the quantitative polymerase chain reaction (qPCR) measurements that have been adopted by the regulatory agencies and pharmaceutical companies? A recent peer-reviewed paper by Speicher, Rose, and McKernan reports that three out of ten lots of Pfizer mRNA vaccines contained residual DNA at the levels that exceeded regulatory limit only when a certain specific set of DNA primers and probe was used [2]. This primer/probe set is designed to detect SV40 promoter/enhancer present in the template DNA of Pfizer mRNA vaccines (but not in the Moderna mRNA vaccines). However, since this primer/probe set targets repetitive sequences within the SV40 promoter/enhancer, two DNA fragments of different sizes may be amplified in the PCR reaction, making it unsuitable for the detection and quantification of specific DNA. Therefore, measurements using this primer/probe set are unreliable, and the conclusion that DNA exceeding regulatory limits was detected by qPCR cannot be supported. When other appropriate primer/probe sets were used, no excess residual DNA was detected. The authors should seriously consider this issue. Another recent preprint paper suggesting that DNA from mRNA vaccines has been integrated into the human genome has also sparked discussion [4]. This paper claims to have detected 20base pairs (bp) of mRNA vaccine-derived DNA in the genome of a bladder cancer patient. However, only the patient’s blood samples were examined, and it remains unclear whether the DNA originated from cancer cells. Most critically, this patient had only received the Moderna mRNA vaccine, yet the sequence of the DNA identified matched that of the Pfizer mRNA vaccine. The mRNA sequences of Moderna and Pfizer vaccines differ due to their respective codon optimization, and the sequence detected in this study has two base mismatches compared to Moderna’s sequence. Furthermore, the nucleotide sequence of the location where the 20bp DNA was inserted into the patient’s genome has not been shown. Which part of which gene in the genome was modified or disrupted? Despite the lack of such details, the authors conclude as if this DNA fragment caused the patient’s cancer. From the perspective of molecular biology and oncology, this might be considered an inadequate and inappropriate study. We have formed a group of interdisciplinary academic researchers in Japan to verify such misinformation. Recently, we experimentally refuted the claim that the presence of DNA contamination in mRNA vaccine formulations leads to the integration of DNA fragments into the genome, thereby altering gene function or expression to induce various adverse events [5]. Misinformation about COVID-19 vaccines has been propagated not only by anti-vaccine scientists, but also by pro-vaccine scientists, such as the prospect of herd immunity and the underestimation of severe adverse effects, represented by myocarditis among young males. Scientists must strive to restore trust in science, which has been lost due to social confusion and division during the COVID-19 pandemic. Conflicts of interest The authors declare no conflict of interest exists. References [1] McKernan K, et al. DNA contamination in mRNA vaccines. OSF Preprints. 2023. Available from: https://osf.io/preprints/osf/b9t7m_v1 [2] Speicher DW, Rose R, McKernan K. Residual DNA in mRNA vaccines: analysis and implications. Autoimmunity. 2025;58(2):e2551517. Available from: https://www.tandfonline.com/doi/full/10.1080/08916934.2025.2551517 [3] Achs M, et al. Residual DNA analysis in mRNA vaccines. Research Square. 2024. Available from: https://www.researchsquare.com/article/rs-7340318/v1 [4] Catanzaro M, et al. Possible genomic integration of vaccine-derived DNA. Zenodo. 2025. Available from: https://zenodo.org/records/17122912 [5] Nitta H, et al. Experimental evaluation of DNA contamination in mRNA vaccines. Jxiv Preprints. 2024. Available from: https://jxiv.jst.go.jp/index.php/jxiv/preprint/view/1428