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35

Answering my own question after reading the 2018 Nature review article “mRNA vaccines — a new era in vaccinology” The resources and motivation engendered by the COVID-19 pandemic are a major factor in the development of the first mRNA vaccines approved by national governments. However, before the COVID-19 pandemic, there were recent advances in mRNA vaccine ...


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I would strongly recommend looking in more detail into available resources for SD and Kozak sequences, wikipedia basically answers these questions and has plenty of further reading if you desire to explore these questions. At the same time, remember that these are statistical processes involving thousands of molecules, rather than deterministic processes ...


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The two stop codons are obviously to prevent read-through of the termination codon. Why this should be necessary is not clear to me, but the following may be relevant: The synthetic mRNA differs from the natural mRNA in a particular respect that is easier to explain with reference to the transcript map of the virus, below. The two ORFs 1a and 1b are ...


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I don't think definite answers exist but I can think of theoretical reasons: First, Poly A tail can efficiently be synthesized because ATP is the most readily available nTP, being the main energy source. More to the mechanism, but this is no explanation to the evolution: The termination sequence 'TTTATT' on the DNA template and 'AAUAAA'on the RNA is the ...


4

This is the temperature at which RNA is stored for long term storage without the occurance of degradation. It is also standard lab routine to store RNA at this temperature. Conviniently, this temperature can be reached by dry ice (-78°C), which makes shipping a lot easier. However, there are indications by Biontech themselves that the vaccine will be stable ...


4

What is Protein Expression Level? This was the original title of the post, which I edited myself because I regard the answer as trivial, but the question as more substantial. To deal with the trivial first: ‘Level’ is not a scientific unit, and can only be used unambiguously as a scientific term in its English sense in relation to liquids, e.g. “The level ...


4

I am asking this question to understand whether the cells which are used to create spike proteins are attacked by the immune system. Yes, that is the aim of RNA vaccinations! But don't worry, that's a good thing, as can be concluded from this review-paper, that emphasizes the advantage of RNA vaccinations to invoke cellular immune response: Although ...


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If I understand your question and graph correctly, your Y-axis is log(x/REF), where REF is some external standard. Your "Ref" on the x-axis you expect to be the same as REF, so that log(Ref/REF) "should be" zero, but you find it is not. However, it looks like the mean(log(Ref/REF)) is still approximately zero. This is what I would expect: ...


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The mRNA won't be entirely perfect, but the imperfections will not matter. The spike protein is big, encoded by thousands of base pairs in the virus. In the virus itself, it's not entirely homogeneous: there are always going to be small mutations that cause different variants to be produced, but nearly all of those are nearly identical. The mRNA in a vaccine ...


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As was observed (by others) under related q's here on material from that site, it seems Pfzier/BioNTech has done a global optimization to increase CG contents in the sequence, generally thought to be beneficial to mRNA expression (in addition to all the other things they've done, like U -> m1Ψ global substitution, specific to mRNA therapeutics). That (...


3

What you describe, creating the spike protein independently and delivering it, is exactly what is done by subunit vaccines, such as the COVID-19 vaccine developed by Novavax. As already noted in @Amanda's answer, mRNA is great at amplifying a delivery, so you need a lot less to be delivered. The manufacturing process for the vaccine itself is a lot more ...


3

The mRNA vaccines encode a mutant version of the spike protein in which the structural transition needed to to fuse membranes is blocked. This was done to make the immune response focus on the pre-fusion state, which is much better for neutralizing the virus. From https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38: Fortuitously, ...


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Tl Dr: In the rosalind example they are showing the 3 reading frames that stem from the definition of a reading frame(non-overlapping triplets), not an example of open reading frames. Open reading frames are non-overlapping triplets between a start codon and a stop codon. Its important to step back and understand what is meant by reading frame first. It has ...


2

Summary Reassignment of an UGA codon as a selenocysteine codon is thought to involve the interaction of obligatory secondary structure elements called selenocysteine insertion sequences (SECIS) with the dedicated translation elongation factor that presents a unique tRNA aminoacylated with selenocysteine to the ribosome. However the location of these elements ...


2

It is entirely possible that different cell-lines express the same genes at drastically different levels. The proteinatlas provides data and analyses on differences between certain tissues or cell types / cell-lines. If your cells are of the same line/tissue, then they might still differ dependent on the cell-cycle, age and external factors. There are ...


2

"On MHC II, do cells present only antigen they have receptors for?" Thank you for boiling your question down to its essence. The answer is no. Professional antigen-presenting cells (APCs) such as macrophages, dendritic cells, B cells, etc., which present peptides in the context of the major histocompatibility complex (MHC) Class II to CD4+ Thelper ...


1

Does the mRNA of the covid19 spike protein contain any nuclear localization signals? I take it you are talking about the coronavirus SARS-CoV-2, and asking whether its RNA genome contains any nuclear localization signals that act post-translationally as signals to specifically import the spike proteins into the nucleus. I cannot find any reports where any ...


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Why is the mRNA not damaged at -70 C temperature Corona vaccine? Actually they use Sucrose as cryoprotectant. https://medicalsciences.stackexchange.com/questions/25289/why-use-sucrose-rather-than-glucose-in-an-injectable-vaccine/25290


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There is a question on stackexchange that is not only related Why cytotoxic T cells don't kill dendritic cells when they present antigen? Your question refers to "some cells" (explanatory text) and "transfected cells". Thus, any cell that takes up the m-RNA-vaccine is referred to. However, any answer must be based on the different ...


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A subgenomic promoter is a promoter added to a virus for a specific heterologous gene, resulting in the formation of mRNA for that gene alone. Many positive-sense RNA viruses produce these subgenomic mRNAs (sgRNA) as one of the common infection techniques used by these viruses and generally transcribe late viral genes. From doi:10.1128/jvi.74.13.5988-5996....


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