Risks associated with mRNA drugs found before the covid vaccines
Between 4-7 Jan 2021 I looked into the potential risks of (m)RNA platforms for drugs/vaccines because they are so new and there hadn't been any phase III trials before 2019.
Several different mRNA vaccines have now been tested from phase I to IIb clinical studies and have been shown to be safe and reasonably well tolerated (TABLES 2, ,3).3). However, recent human trials have demonstrated moderate and in rare cases severe injection site or systemic reactions for different mRNA platforms22,91. Potential safety concerns that are likely to be evaluated in future preclinical and clinical studies include local and systemic inflammation, the biodistribution and persistence of expressed immunogen, stimulation of auto-reactive antibodies and potential toxic effects of any non-native nucleotides and delivery system components. A possible concern could be that some mRNA-based vaccine platforms54,166 induce potent type I interferon responses, which have been associated not only with inflammation but also potentially with autoimmunity 167,168. Thus, identification of individuals at an increased risk of autoimmune reactions before mRNA vaccination may allow reasonable precautions to be taken. Another potential safety issue could derive from the presence of extracellular RNA during mRNA vaccination. Extracellular naked RNA has been shown to increase the permeability of tightly packed endothelial cells and may thus contribute to oedema169. Another study showed that extracellular RNA promoted blood coagulation and pathological thrombus formation 170. Safety will therefore need continued evaluation as different mRNA modalities and delivery systems are utilized for the first time in humans and are tested in larger patient populations.
While preclinical studies have generated great optimism about the prospects and advantages of mRNA-based vaccines, two recent clinical reports have led to more tempered expectations22,91. In both trials, immunogenicity was more modest in humans than was expected based on animal models, a phenomenon also observed with DNA-based vaccines171, and the side effects were not trivial. We caution that these trials represent only two variations of mRNA vaccine platforms, and there may be substantial differences when the expression and immunostimulatory profiles of the vaccine are changed. Further research is needed to determine how different animal species respond to mRNA vaccine components and inflammatory signals and which pathways of immune signalling are most effective in humans.
Cell injury leads to exposure of intracellular material and is associated with increased permeability of vessels in the vicinity of the damage. Here, we demonstrate that natural extracellular RNA as well as artificial RNA (poly-I:C), or single-stranded RNA but not DNA, significantly increased the permeability across brain microvascular endothelial cells in vitro and in vivo.
Here, we present in vivo and in vitro evidence that different forms of eukaryotic and prokaryotic RNA serve as promoters of blood coagulation.
Basically a potential risk for blood clots, possibly in your brain or heart or even lungs, which matches with some of the increased health problems seen.
https://www.annualreviews.org/doi/10.1146/annurev.immunol.23.021704.115843?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed More about interferon potential issues ^