by Sanjukta Mondal, Medical Xpress
edited by Sadie Harley, reviewed by Robert Egan
Schematic of the DMAb technology platform. a) Four synthetic DNA constructs were designed for optimal in vivo expression of the HCs and light chains (LCs) of AZD5396 and AZD8076. b) pAZD5396, and pAZD8076 were administered separately with an in vivo electric pulse. Credit: Nat Med (2025). DOI: 10.1038/s41591-025-03969-0
A new way to deliver protective antibodies against COVID-19 was tested in a Phase I clinical trial. Instead of injecting pre-made antibodies into patients, this approach encouraged the body to produce its own antibodies to fight off the disease-causing viruses.
In this study, the researchers injected DNA-encoded monoclonal antibody (DMAb)—synthetic plasmid DNA carrying genetic instructions for antibodies—that can neutralize SARS-CoV-2 directly into muscle tissue of 44 healthy adults aged 18–60 years.
The outcomes demonstrated a clear proof-of-concept for DMAb, as the platform was safe and well tolerated with no product-related adverse events.
The findings are published in Nature Medicine.
mRNA vaccines, which played a pivotal role in controlling the pandemic, continue to serve as the primary line of defense against COVID-19. However, the vaccines do not trigger an adequate immune response in some people, which leaves them vulnerable to infections.
Studies have shown that monoclonal antibody (mAbs) therapies that use lab-made proteins to mimic natural antibodies to trigger an immune response to attack specific targets can be a promising alternative.
Current mAb treatments, while powerful, come with practical challenges. These therapies rely on delicate proteins that must be kept cold from the lab to the patient, making global distribution especially in low-resource areas quite difficult. Their protection fades over time, pushing scientists to search for ways to make their effects last longer in the body.
The researchers presented synthetic DMAbs as the potential solution to the existing problems. DMAbs are cheaper to produce mAbs and rely on DNA-encoded instructions to generate antibodies within the body rather than on pre-made proteins. As a result, the platform can be easily scaled and transported without cold-chain storage.
Due to their lucrative properties, many studies have explored how this therapy fares against the COVID-19 virus, but not much is known about how the body reacts to them. This Phase I trial aimed to fill that gap by testing whether this DNA-based antibody treatment could be safely given to humans and how it behaved in the body over time.
The study followed a dose-escalation approach, where the researchers gradually increased the treatment dose in different groups to identify the highest level that could be safely administered without significant side effects.
Participants received one to four doses of the treatment through intramuscular injection of DNA encoding two SARS-CoV-2 neutralizing mAbs, AZD5396 and AZD8076. This was followed by a brief electrical pulse—known as electroporation—to help the DNA enter their cells.
The trial began with 44 participants, though five withdrew early. The remaining 39 were closely monitored over 72 weeks to track both the systemic side effects of the treatment.
The most common reactions were mild and short-lived, mainly pain or redness at the injection site that faded within minutes.
Overall, the DMAb platform was well tolerated, with no product-related serious adverse events reported. Importantly, researchers found no anti-DMAb antibodies in any participant, suggesting the body did not mount an immune response against the treatment itself.
Unlike traditional monoclonal antibodies, whose effects wear off relatively quickly, the DMAb-generated antibodies remained active for the full 72 weeks.
Researchers believe this study validates DMAbs as a genuine alternative to conventional antibody therapies. By offering lasting protection without the cost or logistical burdens of traditional mAbs, this approach could transform treatment for diseases beyond COVID-19.
Written for you by our author Sanjukta Mondal, edited by Sadie Harley, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You’ll get an ad-free account as a thank-you.
More information: Pablo Tebas et al, Safety and pharmacokinetics of SARS-CoV-2 DNA-encoded monoclonal antibodies in healthy adults: a phase 1 trial, Nature Medicine (2025). DOI: 10.1038/s41591-025-03969-0
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