Department Cell Biology
Principal investigator Maarten Fornerod
E-mail address m.fornerod@erasmusmc.nl
Gene regulatory elements in plasmid vaccine DNA templates
Modified mRNA corona vaccines have been rolled out to billions of people worldwide with limited quality control and limited short and long term safety assessment. Consequently, unexpected quality issues and adverse side events appear in real world data. Signals of poor quality control include mRNA size heterogeneity and unequal distribution of adverse events across vaccine batches.
Recently, significant transfection competent DNA contamination has been detected in all mRNA vaccines studied, suggesting risk of vaccine receipient genome damage. Importantly, the majority of contaminating DNA was found to be present as 100-300 bp fragments, meeting the size of many gene regulatory elements – promoters and enhancers. These are usually in the 50-1000 bp range. While some of vaccine template plasmid derived fragments are known to be biologically active when integrated into the human genome, most notably the SV40 promoter region present in Pfizer plasmid DNA, cryptic eukaryotic regulatory elements are known te exist within bacterial plasmid sequences. In addition, cryptic regulatory sites may be present in the spike protein coding region.
The project aims to predict and test eukaryotic promoter and enhancer elements in plasmid vaccine DNA templates using deep learning approaches and experimental STARR-seq analysis to test the presence of enhancer sequences in various relevant cell types.
Techniques
- DeepSTARR
- STARR-seq