Pursuant to the order issued on March 16 in American Academy of Pediatrics et al. v. Kennedy et al., No. 1:25-cv-11916 (D. Mass.), the ACIP meeting previously scheduled for March 18-19 has been stayed until further notice. 

In light of this notice, I want to outline what should have been addressed at this meeting and what still demands attention: DNA contaminants and byproducts in the Covid-19 mRNA vaccines.

mRNA vaccines were introduced as a technological breakthrough. They were rapidly developed, widely deployed, and presented as rigorously evaluated. But years into their global use, a basic scientific question still remains unresolved: What is the biological fate of the DNA byproducts known to be present in these vaccines?

This is not a speculative concern. The manufacturers acknowledge that their production process generates DNA byproducts in their publications and patents. Independent and regulatory laboratories have confirmed their presence in vaccine vials. And yet despite this, the FDA and the manufacturers have not publicly provided data addressing the fate, persistence, or appropriate safety thresholds for DNA encapsulated in LNPs present in mRNA vaccines. The manufacturers state that they provide data to the FDA in accordance with existing guidance. This combination— acknowledgment, confirmation, and absence of data—should give pause.

Pfizer and Moderna have been clear in their own scientific literature describing the manufacturing process used to produce mRNA vaccines. The process of in-vitro transcription generates nucleic-acid byproducts in the form of residual DNA fragments, double-stranded RNA, and RNA:DNA hybrid molecules. Pfizer and Moderna also acknowledge that these byproducts are not expected to be completely removed during purification.

Further, both companies have described how such nucleic-acid structures can interact with innate immune sensing pathways if present inside cells. None of this is controversial. It is very well-established molecular and cellular biology, and it is the manufacturers’ own description of their technology. In other words, the existence of these byproducts, and their potential biological relevance, is not in dispute, although based on the media and public narrative, you might think otherwise. 

Multiple laboratories, including both independent researchers and government-affiliated labs in Germany (PEI) and Australia (TGA), have directly analyzed vaccine vials. Their findings are consistent. DNA fragments are present in all tested vaccine lots and the fragments vary in size, with some extending into the kilobase range. Sequencing reveals DNA derived from across the original DNA template, including Spike-encoding sequences, and regulatory elements such as the SV40 promoter (in the Pfizer construct).

More importantly, several analyses have reported that DNA corresponding to the spike sequence appears at substantially higher levels than plasmid backbone. This matters, because most routine testing focuses on backbone markers potentially underrepresenting other DNA species that may be more abundant. And this means that the DNA being measured may not fully reflect the total amount of DNA that is present.

Given these findings, one might reasonably expect the FDA and the manufacturers to have performed comprehensive studies measuring how much spike-sequence DNA is present in finished vaccine products. One might expect data collected on whether RNA:DNA hybrid byproducts are being systematically measured, or what happens to LNP-encapsulated DNA fragments after they are delivered into cells. It would be expected that data exists related to whether the DNA persists in tissues, or whether it interacts with or integrates in the human genome. And one should reasonably expect that safety thresholds and guidance specific for lipid nanoparticle delivery of DNA would have been established prior to, or at least immediately following the vaccine rollout.

And yet, six years later, there is still no publicly available, comprehensive data either from the FDA or the manufacturers that answers these questions.

Most public discussion of mRNA vaccine DNA focuses narrowly on plasmid backbone DNA. Far less data and information are available regarding spike-derived sequences, despite clear reasons to expect their presence, and clear potential health implications. Equally important, there is no transparent, product-specific framework defining acceptable levels of these byproducts for mRNA vaccines.

As has been written in prior contexts, the regulatory standards for residual DNA were developed for an earlier generation of vaccines and biologics that do not deliver nucleic acids into cells. Yet mRNA vaccines do exactly that. They are designed to transport nucleic material into human cells efficiently. That is their mechanism of action. It is obvious that legacy DNA thresholds are inappropriate in this new context. And this has notably been acknowledged in 2022 by the WHO in after the mRNA vaccines were globally deployed. So how is it that years later, there is still no clearly articulated, publicly available framework governing these byproducts? Moreover, how is it that we do not have answers to questions that are easily addressable? 

The tools to answer these questions already exist. Modern sequencing, molecular quantification, and cell-based assays are widely available, relatively low-cost, and straightforward to perform. The issue is not feasibility; it is transparency. Have these analyses been done, and if so, why have the results not been clearly presented?

At a minimum, the public and the scientific community should expect a clear answer to a basic question: When DNA fragments are delivered into human cells as part of a medical product, what happens to them? The path forward is to measure all relevant DNA species, including spike-associated sequences. Evaluate their persistence and biological behavior. Define appropriate safety thresholds for this specific platform. And most importantly, make those data publicly available. Not as reassurance, but as evidence.

The fact that this has not been addressed years into global deployment is not a minor oversight. It is a fundamental failure of scientific and regulatory transparency.