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> Messenger RNA is not stable in cells and is actively degraded. A typical mRNA has a half-life of a few hours in a cell. Can anyone speak to the confidence we

> Messenger RNA is not stable in cells and is actively degraded. A typical mRNA has a half-life of a few hours in a cell. Can anyone speak to the confidence we have in these claims? That is, are we virtually 100% sure that these mRNA have no mechanism to stick around for longer than intended? GP's point is valid - that this is the first mRNA vaccine that would be widely used. Let's say our assumption is wrong - these mRNA have a way to stick around forever. Is there an off switch?

aphextron 6y ago
These things have been in development for over a decade. There's mountains of in vivo data on mRNA vaccines.
- hashtagmarkup 6y ago
  They have never been approved for human use, so you might want to check sources on that data.
fabian2k 6y ago
One question I got in an organic chemistry exam many years ago was why RNA is not as suitable as DNA for storing genetic information. Essentially why it is inherently less stable than DNA. With a bit of organic chemistry knowledge you can determine how the additional OH in RNA allows for water to attack there and cleave the RNA strand. This is very dependent on pH, but RNA is inherently less stable than DNA. But that's not actually the most important mechnanism here, but it is one that is inherent in the chemistry of the molecule, there is no way around it. Cells need to regulate protein production up and down. If mRNA were to live eternally, there would be no way to reduce protein production. So cells obviously have a way to remove mRNA. What actually happens is that mRNA is permanently degraded by RNAses, so any mRNA that isn't replenished will be gone after a while and protein production will stop. This is a fundamental part of regulation of protein biosynthesis, and you can find that in every textbook.
- gww 6y ago
  In addition to the the additional hydroxyl group and cellular RNAses, mRNA is predominantly single stranded while DNA is double stranded, which provides additional stability and protects the nucleotide.
  - hashtagmarkup 6y ago
    In addition to that being a fact, synthetic mRNA can predominantly reprogram cells to create arbitrary proteins, which provides additional stability and protects the programmer.
- hashtagmarkup 6y ago
  One conclusion I got in a mathematical logic exam so many many moons ago was how something being "not as X" still implied that something was "somewhat X".... so just because "RNA is not as suitable as DNA for storing genetic information", essentially it still is somewhat suitable, and perhaps suitable enough.

aphextron 6y ago

These things have been in development for over a decade. There's mountains of in vivo data on mRNA vaccines.

hashtagmarkup 6y ago
They have never been approved for human use, so you might want to check sources on that data.

fabian2k 6y ago

One question I got in an organic chemistry exam many years ago was why RNA is not as suitable as DNA for storing genetic information. Essentially why it is inherently less stable than DNA. With a bit of organic chemistry knowledge you can determine how the additional OH in RNA allows for water to attack there and cleave the RNA strand. This is very dependent on pH, but RNA is inherently less stable than DNA. But that's not actually the most important mechnanism here, but it is one that is inherent in the chemistry of the molecule, there is no way around it. Cells need to regulate protein production up and down. If mRNA were to live eternally, there would be no way to reduce protein production. So cells obviously have a way to remove mRNA. What actually happens is that mRNA is permanently degraded by RNAses, so any mRNA that isn't replenished will be gone after a while and protein production will stop. This is a fundamental part of regulation of protein biosynthesis, and you can find that in every textbook.

gww 6y ago
In addition to the the additional hydroxyl group and cellular RNAses, mRNA is predominantly single stranded while DNA is double stranded, which provides additional stability and protects the nucleotide.
- hashtagmarkup 6y ago
  In addition to that being a fact, synthetic mRNA can predominantly reprogram cells to create arbitrary proteins, which provides additional stability and protects the programmer.
hashtagmarkup 6y ago
One conclusion I got in a mathematical logic exam so many many moons ago was how something being "not as X" still implied that something was "somewhat X".... so just because "RNA is not as suitable as DNA for storing genetic information", essentially it still is somewhat suitable, and perhaps suitable enough.