Can ribonucleic acid be made into a life saving medication?

TeachableMedicalNews article 01172020

Teachable moment in classrooms:

1. chemical basis of life chapter – biological use of the lipid, cholesterol
2. cellular basis of life chapter – small interfering RNA can stop protein synthesis
3. cellular basis of life chapter – LDL binding to LDL receptor before endocytosis
4. digestive system chapter – cholesterol transporter LDL is made in the liver

The news item:  Several new cardiovascular medications were discussed in a recent article:

https://www.cbs17.com/news/new-and-old-drugs-may-offer-new-ways-to-fight-heart-disease/

The article mentions the beneficial LDL-reduction from RNA-interference drug inclisiran.

So, Why Do I Care??  Currently about 71 million adults in the US have higher than normal LDL levels.  In 2017 in the US 365,000 people died of coronary artery disease, mostly caused by high cholesterol and LDL.   Each year almost 800,000 people in the US suffer a stroke.  Treatments that further lowers LDL and cholesterol levels can save great many lives.

Plain English, Please!!!  First, let’s talk about cholesterol and LDL. Cholesterol is a natural lipid that is essential for functioning of all cells, and also used for steroid synthesis.  To distribute cholesterol in our bodies, the liver packages cholesterol into cargo boats called LDL, or low density lipoprotein.

Second, let’s talk about the removal of LDL from the blood stream.  The LDL boats are removed from the blood by LDL-receptors.  Imagine a harbor on the cell membrane where the boats match the shape of the docks.  For the LDL boats, the LDL receptors are the docks.  As it turns out, there is a protein, PCSK9, in our body that destroys the docks, so when the LDL boats can’t dock, they keep on floating around in the blood stream, and cause damage to blood vessels. The more PCSK9 proteins we have in our body, the higher the blood LDL and cholesterol levels spike, and the more strokes and heart attacks we may suffer.

Third, let’s talk about RNA interference. It makes sense, that we can lower blood LDL and cholesterol, when we remove as much PCSK9 protein as we can.  One way to keep PCSK9 levels low is to slow the protein production.  PCSK9 protein is made, just like other proteins, from a messenger RNA (mRNA) that orders the amino acids with the help of a ribosome.  Imagine mRNA as a string of letters forming a message on a long banner. The RNA interference drug inclisiran covers up a long part of the banner, and makes the message impossible to read. So, with inclisiran stuck to mRNA, the ribosome cannot make a functional PCSK9 protein.