Gene-Based Anti-SARS-CoV-2 Prodrugs and Considerations Regarding Genetically Modified Organisms

ABSTRACT
During the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), novel gene-based anti-SARS-CoV-2 prodrugs (ASPs) were used. ASPs introduce foreign, genetically modified material (e.g., modified mRNA, mod-mRNA) into human cells to induce them to produce a foreign SARS-CoV-2-like spike protein (SP), which is intended to trigger an immune response against SARS-CoV-2. This process meets aspects of the biological definition of a genetically modified organism (GMO). It has been shown that modmRNA-based ASPs can be converted into DNA by reverse transcriptase. Plasmid DNA contamination has also been found in mod-mRNA-based ASPs. Both aspects open up the theoretical possibility that genetic material from ASPs could enter the human cell nucleus and be incorporated into the human genome – another GMO criterion. Furthermore, it has been shown that biological effects of gene-based ASPs can be passed on to offspring (probably epigenetically) – another GMO criterion. Even if ethical and legal considerations currently rule out the classification of humans as GMOs, the biological consideration raises complex questions that necessitate a comprehensive and critical scientific and societal debate about such gene-based technologies.