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For biodistribution, Pfizer did not use the actual spike mRNA product in their studies. Instead, they substituted in a luciferase reporter mRNA packaged in the same lipid nanoparticles. This approach allowed them to track where the mRNA traveled in rodents. The studies showed that following intramuscular injection, most of the mRNA remained at the site of injection, but there was also notable levels detected in the liver. Despite the limitations of this approach, which can underestimate low level or transient distributions to other tissues, it nevertheless showed that the vaccine components do not remain confined to the injection site.
Next slide. For Moderna, no dedicated biodistribution study was performed with the COVID mRNA itself. Instead, data was provided from a surrogate product, a CMV mRNA, mRNA-sixteen 47, which used the same lipid nanoparticle formulation. In their rat study, after intramuscular injections, high levels of the mRNA were detected at the injection site, but also in multiple organs such as the draining lymph nodes, spleen, eye, and liver. Lower levels were also found across a wide range of tissues, including the heart, lungs, testes, and brain.
Importantly, this study clearly showed that the mRNA can cross the blood brain barrier. Next slide. Consistent with what is seen in animal studies, the vaccine mRNA and its spike protein have been detected in humans across multiple tissues, including blood, lymph nodes, the heart, and even the brain. These findings make it clear that the mRNA does not remain confined to the injection site. Importantly, persistence has been documented well beyond the initial hours or days, lasting weeks in some tissues, and in certain studies detectable for many months.
Next slide. To summarize the biodistribution data, it's important to note that neither Moderna nor Pfizer used their actual commercial mRNA vaccine products in the preclinical biodistribution studies. Instead, they relied on surrogate construct packaged in same or similar lipid nanoparticles. Second, the results of those studies show that the mRNA and lipid nanoparticles were not confined to the injection site. Systemic distribution was observed with evidence that the mRNA can cross the blood brain barrier.
Consistent with these findings, studies in humans have confirmed that vaccine mRNA can be detected in multiple tissues, including lymph nodes, the heart, the central nervous system, and blood. Finally, persistence is not just short term. In some reports, mRNA has been detected for weeks to months, and in certain cases as long as seven zero six days post vaccination. Taken together, these data highlight that biodistribution is broad and persistence is longer than initially expected, raising important questions and concerns for ongoing research and safety monitoring.