system
Given the following post, respond as if you're commenting on Reddit:
human
How do mRNA vaccines avoid being chopped up by the human body's cell enzymes?

I read this passage in a NYT article:

> The mRNA molecules our cells make can only survive a matter of minutes. **The mRNA in vaccines is engineered to withstand the cell's enzymes a bit longer,** so that the cells can make extra virus proteins and prompt a stronger immune response. But the mRNA can only last for a few days at most before they are destroyed.

How does this work? What is it about particular strands of mRNA that makes them accessible for protein production but also prevents them from being destroyed for a while?
gpt
Naked RNA would be rapidly degraded by exonucleases before it entered the cell.  To prevent this, the mRNA is enclosed in lipid nanoparticles that protect it from extracellular RNAses and also helps it transfect (get into) the cells it needs to enter.  mRNA is supposed to come from the nucleus - any mRNA that comes from outside the cell is a hallmark of a virus and is going to trigger some anti-viral responses.  The lipid nanoparticles also help protect the RNA from some of the receptors (like TLR 7 and 8) that would otherwise trigger antiviral responses that could shut down translation and speed up degradation of the mRNA.

Once it is inside the cell, the mRNA will be translated into spike protein by ribosomes and the proteins will then be processed and presented on MHC-I and II molecules so that T-cells can be activated (just as happens with natural viral proteins).

The mRNA will eventually be degraded by endonucleases.  This is *normal*: it limits potential adverse effects, you don't want the mRNA hanging around and being translated forever!  But you also want to be sure that it isn't degraded *so* rapidly that barely any spike protein gets made and the adaptive immune response isn't sufficiently activated.

There are a number of methods that can be used to increase the stability and half-life of the mRNA by making it harder for certain RNA-degradation processes to work and/or increasing the efficiency of translation prior to degradation.  For example, you can elongate the poly-A tail, or modify the 5' cap, or make nucleotide modifications.

The Pfizer vaccine makes a few nucleotide modifications (with single incorporations of 1-CH3-pseudouridine) which helps prevent innate immune responses from destroying the mRNA before it can be translated, and also increases its translation.  It's believed that the increased translation is because it decreases the hydrolysis of the mRNA by phosphodiesterases.  

Both vaccines also use similar consecutive proline substitutions to force the relevant spike protein chains into more stable pre-fusion conformations.  By stabilizing the protein product in this way, mRNA can be active for a shorter time because the protein product is more likely to stimulate the correct immune responses.