A new DNA-based treatment approach could revolutionize the way the body defends itself against infection with SARS-CoV-2, the virus that causes Covid-19. Instead of receiving lab-made antibodies, patients could be helped to produce the necessary antibodies themselves, providing longer protection and reducing treatment costs.
A phase I clinical trial tested an experimental therapy called DMAb (monoclonal antibody encoded in DNA), which uses synthetic plasmids – small fragments of DNA synthesized in the laboratory – that contain the genetic instructions for producing antibodies capable of neutralizing SARS-CoV-2.
The therapy was administered by intramuscular injection to 44 healthy volunteers aged between 18 and 60 years.
The researchers used two types of genetically encoded antibodies, AZD5396 and AZD8076, delivered separately by injection, followed by a brief electrical stimulation (electroporation) designed to facilitate the entry of DNA into cells. The study followed a dose-escalation schedule to establish the maximum dose that can be administered safely.
The results showed that the DMAb platform is safe and well tolerated, with no serious product-related adverse reactions. The most frequent effects were minor: local discomfort or redness, which disappeared quickly. Of the initial 44 participants, 39 completed the full 72-week follow-up.
A key observation was the absence of antibodies directed against DMAb in the body, suggesting that the immune system did not perceive the therapy as a foreign substance.
In addition, the antibodies generated by this method remained active for the entire duration of the study, i.e. more than a year and a half, which represents a significantly superior performance to traditional monoclonal antibodies, which lose their effectiveness after a few months.
Monoclonal antibody therapy (mAbs), previously used in the fight against Covid-19, involves the administration of fragile proteins that require strict refrigeration and transport conditions.
In contrast, DMAb therapy does not require cold storage, because the genetic material that encodes the antibodies can be stored and transported easily, and the body itself produces the antibodies after administration.
This technology could have applications far beyond the recent Covid-19 pandemic, providing an adaptable platform for combating other viral infections or even chronic diseases.
Although DMAb therapy is still in the early stages of evaluation and has not been approved for clinical use, the results of this first study demonstrate that the method is safe and can be successfully applied in practice.
The research was recently published in the journal Nature Medicine and represents an important step towards a new generation of experimental therapies that use synthetic DNA to produce antibodies, which could radically transform the way medicine prevents and treats infectious diseases.
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