I'm not sure I understand the question, as that's the point of the article. Clinical trials are currently testing mRNA to produce proteins to treat cystic fibrosis, heart failure and various obscure conditions. There are various problems, such as ensuring the the protein is created in the right cells, requiring repeated doses so the protein is created over a long time, handling side effects, and increasing the amount of protein created. So mRNA isn't an easy solution.

This is Moderna's goal https://www.modernatx.com/mrna-technology/mrna-platform-enab...

Yeah, that's basically what the article discusses. It will be easier for non-targeted treatments that can circulate the whole body. This tech (by itself) doesn't really solve the issue of delivering site-specific medication.

> given we can predict what shape of protein an mRNA strand would produce

For therapeutic proteins you usually work the other way around: You design the shape and try to get a sequence that folds as intended. In other words, the inverse folding problem.

Yes, and no. The principle is there, but it is important to understand that each cell type is essentially a specialist factory to produce proteins, and the drug may be produced best when you get exactly the right factory to produce the protein (I’m thinking about PTMs). If your body is flooded by inferior product from the wrong factories, the effect of the superior product may be inhibited of diluted.

That said, I can imagine once we figure out how to deliver the mRNA to precisely the right targets, this would be a lot easier (eg engineering receptor ligands onto the mRNA lipid delivery particles).

On face value, it sounds less risky than the standard vaccine development route, which may involve introducing immortalized (i.e. cancerous) cells or artificially stimulating an immune response with known toxins (adjuvants).

I still have questions about the mRNA vaccine concept. Maybe some well-informed HNer can shed light?

1. If the goal is to get the desired protein inside the patient's body, why is injecting mRNA that produces the protein more effective than simply introducing the protein itself?

2. How does the patient's immune system know to treat this protein as unwanted if it's being produced by the body's own cells?

3. How do vaccine developers avoid creating an over-active immune response in the patient (i.e. an allergy)?

A layman's speculation followed by a layman's (at least in terms of immunology) question: introduce a novel mRNA, cells produce novel protein, it is presented to the immune system as something to foment a defense again: vaccine. But the article talks about using this mechanism to replace a functional copy of a genetically missing enzyme. How is it assured that this will assume the opposite goal and not become another target for the immune system to guard against?

On the opposite side: how do we effectively convince people this new type of vaccine is safe long-term? I'm not a biology person, so I trust the biology people when they say it's safe, but many don't.

My intuition is that many cancers can start when proteins are mis-copied, and mRNA therapy seems to rely on copying to work very reliably. Does introduced mRNA increase the risk or impacts of mis-copying?

Is there an ELI5 intuition for why mRNA therapy is safe and won't lead to cells becoming cancerous?

Seems to be working well so far for COVID vaccines. We're about to witness a very large scale test though.