How do DNA and RNA vaccines work?

In a post just published I described the different approaches to making vaccines against Covid-19.  For many of the readers of this blog I appreciate that the concepts RNA and DNA vaccines may be difficult to understand. I have attempted in this post to give, hopefully, an easy to follow introduction to the science behind these different approaches. 

How DNA and RNA make proteins, such as the spike protein   

• Think of a protein as a string of beads, with the each individual bead being one of a chemical called amino acids

• There are 20 different amino acids and all proteins are made of long strings of these in different orders
  • Insulin is a simple protein which has two strings of around 20-30 amino acids
  • The spike protein in Covid-19 virus has 1190 amino acids!
• The clever thing is how all our cells are able to produce individual proteins with exactly the right sequence of amino acids
• This is how it happens:
• Imagine you have a box of 20 different colours of beads then the issue is where are the instructions to put the different beads in the right order
• This is where DNA and RNA come in, they provide these instructions

How do the DNA and RNA instructions work?

• In 1953, in the greatest of all scientific discoveries, Watson and Crick solved this question

• Each of our genes is made up of its own string of DNA, that contains instructions for making proteins, each protein having its own set of DNA instructions
• A gene thus needs to be long enough to match the protein it is going to produce (genes are actually even longer than that but that is another topic!) 
• Genes however do not have 20 different building blocks to match the 20 amino acids, they just have 4 chemicals (called nucleotides)
• Scientists refer to them by the first letter of their chemical name (‘A’, ‘C’, ‘G’ and ‘T’) (many geneticists do like their G&T’s!).  I am going to use the four primary colours to represent these 4 chemicals

• The instructions for each of the 20 amino acids is represented in DNA by a unique sequence of 3 of these 4 chemical.
• As examples:
  • one amino acid may be formed by the sequence ‘Green/Green/Blue’
  • another amino acid may be formed by the sequence ‘Red/Yellow/Green’
• As you can imagine, some genes can be very long and the number of the individual nucleotides can be several thousands
• Thus the entire DNA string can be very long and could easily get damaged so to make it stronger
  • The complete DNA sequence is not actually in the form of a long string but in a tightly bound spiral or helix 
  • Watson and Crick showed was that the stability of DNA was also increased by DNA being two spirals bound to each other (became known as the ‘double helix’)
• The tight binding was a result of the pairing of these 4 chemicals, so ‘Blue’ always paired with ‘Green’ and ‘Yellow with Red’ (actually ‘A’ with ‘T’ and ‘C’ with ‘G”)

The tight binding was achieved by chemical bridges between these pairs 

• So using my colour analogy the sequence:

red-blue-red-yellow-blue-red-green on one spiral

would be bound on the other spiral to the sequence

yellow-green-yellow-red-green-yellow-blue

• Because of these bridges DNA is very stable and can last for ever – scientists have extracted DNA from Egyptian mummies!
• But because DNA is in this very stable form, it cannot produce proteins on its own and this is where RNA comes in 
• What happens is that when DNA wants to start producing a protein, its two spirals separate and the individual spirals hang around waiting for an messenger
• That messenger is RNA which starts forming the ‘lost second spiral but in this case the RNA is not bound to the DNA and, when it is fully formed, it breaks free
• I like this picture which shows how the RNA molecule is produced from DNA

• Then the RNA can do its main work to produce a protein, by using the same 3 letter codes to build up the protein, one amino acid at a time, until the protein is fully formed
• Thus giving a vaccine which is just RNA will start producing the spike protein exactly as it should be!
• By contrast a DNA vaccine could make an error (or two) in making the RNA.

You can now read the post about two new vaccines with a professional eye!

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