![Synthetic mRNA Vaccines and Transcriptomic Dysregulation: Evidence from New-Onset Adverse Events and Cancers Post-Vaccination[v1] | Preprints.org](https://rdl.ink/render/https%3A%2F%2Fwww.preprints.org%2Fimg%2Fpreprints_new.png?width=92&height=&ar=&mode=&format=avif&dpr=2)
Synthetic mRNA Vaccines and Transcriptomic Dysregulation: Evidence from New-Onset Adverse Events and Cancers Post-Vaccination[v1] | Preprints.org
Background/Objectives: Synthetic mRNA vaccines have raised concerns regarding prolonged spike protein expression, immune activation, and potential off-target effects. This study investigates transcriptomic alterations in individuals with new-onset adverse events or cancer following mRNA COVID-19 vaccination. Methods: Bulk RNA sequencing was performed on peripheral blood from two patient groups: individuals with new-onset nonmalignant adverse events and individuals newly diagnosed with cancer post-vaccination. A control group of healthy individuals was used for comparison. Differential gene expression was analyzed using DESeq2, and Gene Set Enrichment Analysis (GSEA) was conducted using the MSigDB database and custom gene sets. Results: Both vaccine patient groups displayed widespread transcriptional dysregulation. In the nonmalignant adverse event group, hallmark enrichments included mitochondrial dysfunction, proteasome-mediated stress, transcriptomic instability, and systemic inflammation. The cancer group exhibited additional hallmarks of genomic instability, and epigenetic reprogramming. Nonsense-mediated decay (NMD), ribosomal stress, and MYC activation were prominent in both groups, while immune signaling via TLRs and type I interferons was particularly elevated in cancer patients. Conclusions: The observed transcriptomic profiles indicate persistent cellular stress responses, mitochondrial dysfunction, and immune dysregulation following exposure to mRNA vaccines, potentially in susceptible individuals. Shared and distinct molecular signatures in both cohorts demonstrate underlying mechanisms contributing to post-vaccine symptomatology and complications, including oncogenesis and or progression of malignant disease. These findings underscore the need for a deeper investigation into the long-term safety of mRNA vaccines and host response variability.
