3 ms·

What is the error rate in mass production of mRNA? What can mRNA with a few flipped/wrong molecules do?

shellfishgene 6y ago
There are various options for RNA polymerases commonly used in vitro [1], generally the error rate is considered to be "pretty low", something like 1 in 10k. An error will also have to result in a change of amino acid, which less likely due to the redundancy of the code. So any error mRNA will probably only have one amino acid changed. This could cause the resulting spike protein to aquire some new characteristic, but it's not very likely I would guess. Also, in the clinical trials they test the actual produced vaccine, with all errors included. [1] https://international.neb.com/tools-and-resources/selection-charts/rna-polymerase-selection-chart https://international.neb.com/tools-and-resources/selection-...
- shellfishgene 6y ago
  Thinking about this some more, there may even be an advantage: The virus also mutates, so some error mRNAs may actually confer additional immunity to future or current virus strains. In reality there are probably way to few errors for this to make a difference...
LarvaFX 6y ago
Genetic code is highly redundant. A few flipped characters will therefore probably not affect the produced protein much.
- shellfishgene 6y ago
  I wouldn't call it "highly" redundant, more than two thirds of mutations will cause an amino acid change.
- thamer 6y ago
  It's highly redundant when there are 2 strands, as is the case with DNA. RNA has a tendency to accumulate mutations quickly, as evidenced by the many hundreds of variants of SARS-CoV-2 that have already been sequenced (and that's with only ~30,000 bases).
fabian2k 6y ago
You have to keep in mind that there are lots of individual mRNA molecules in each vaccine. So an error won't affect all of them, but only a tiny fraction of the total vaccine. The error rate overall should be similar or lower than the error rate for any other mRNA and the viral RNA. The mRNA in the vaccine is not produced chemically, but with an enzyme (polymerase) like mRNA in cells.

There are various options for RNA polymerases commonly used in vitro [1], generally the error rate is considered to be "pretty low", something like 1 in 10k. An error will also have to result in a change of amino acid, which less likely due to the redundancy of the code. So any error mRNA will probably only have one amino acid changed. This could cause the resulting spike protein to aquire some new characteristic, but it's not very likely I would guess. Also, in the clinical trials they test the actual produced vaccine, with all errors included. [1] https://international.neb.com/tools-and-resources/selection-charts/rna-polymerase-selection-chart https://international.neb.com/tools-and-resources/selection-...

shellfishgene 6y ago
Thinking about this some more, there may even be an advantage: The virus also mutates, so some error mRNAs may actually confer additional immunity to future or current virus strains. In reality there are probably way to few errors for this to make a difference...

LarvaFX 6y ago

Genetic code is highly redundant. A few flipped characters will therefore probably not affect the produced protein much.

shellfishgene 6y ago
I wouldn't call it "highly" redundant, more than two thirds of mutations will cause an amino acid change.
thamer 6y ago
It's highly redundant when there are 2 strands, as is the case with DNA. RNA has a tendency to accumulate mutations quickly, as evidenced by the many hundreds of variants of SARS-CoV-2 that have already been sequenced (and that's with only ~30,000 bases).

fabian2k 6y ago

You have to keep in mind that there are lots of individual mRNA molecules in each vaccine. So an error won't affect all of them, but only a tiny fraction of the total vaccine. The error rate overall should be similar or lower than the error rate for any other mRNA and the viral RNA. The mRNA in the vaccine is not produced chemically, but with an enzyme (polymerase) like mRNA in cells.