Thread by @BenjaCurrents

This FDA paper from July 2020 makes some very interesting points about mRNA vaccines
"Replacing rare codons with those used more frequently does not always produce the desired effects"
europepmc.org/article/med/32…

"For example if translation is too rapid, the protein might not fold correctly into a functional antigen, and this can have the undesired consequences of reducing
vaccine efficacy"

"The other modification required for production of a stable mRNA is the addition of the poly(A) tail. The length of the poly(A) tail can affect the translation efficiency, and thus, the expression level of the protein, and therefore, needs to be considered"

"Several mRNA versions of the antigen gene may need to be evaluated in preclinical toxicology and immunogenicity studies."

"If the LNPs contain a lipid component that is not a natural chemical but instead is a novel compound that has not been a part of another drug used in humans, it may need to be tested for toxicity, particularly as some cationic lipids have been found to be toxic in vivo"

"A toxicology study of a mRNA vaccine would generally include an assessment of the reactogenicity of the vaccine in a relevant animal model. However, because the mouse and human immune systems are not always concordant the assessment of potential reactogenicity can be complicated

"A lipid-based particle encapsulating the mRNA might facilitate passage to distant organs and result in longer retention times. For this reason, biodistribution and retention studies have been requested for mRNA vaccines."

@2Genervter @JikkyKjj @Kevin_McKernan @Clucky92864053 @fx_alluka @gutwat1 @eh_den