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Comment by xiphias2 | Hacker News Reader

The exciting thing with mRNA vaccines is that while developing the delivery platform took decades, developing the COVID vaccine itself was just 48 hours according to the CEO of both Moderna and BioNTech. Right now they have a lot of work with manufacturing (and they had lots and lots of paper work to do), but even there I think they are doing great, as they were not prepared for a pandemic.

As the drug delivery platform is working great, it seems like it can be reused (unlike with older platforms), and the hardest part of developing new mRNA vaccines is to research the genetic code to put in it.

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It is exciting. But what's a bit unclear (to me) is how re-usable safety testing is. Are we going to arrive at stage where we can "push to production" after this 48 hour design phase, or are we going to need months-to-years of trials for each new code?

There's a huge difference between months and years.

The delivery platform is reusable, which is a big difference from older vaccines, where the virus that is delivered can be used only once (Sputnik-V vaccine uses 2 different delivery platforms _because of_ this.

The other thing to look at is efficiency: as the vaccines can deliver mRNAs that cells express anyways in healthy people, the lesser toxicity can mean a higher likelihood of success for the drug (which is the main problem with drug development in the last 10-20 years).

>As the drug delivery platform is working great, it seems like it can be reused (unlike with older platforms), and the hardest part of developing new mRNA vaccines is to research the genetic code to put in it.

While we're all cheering for its success, its important to remember that the current authorization was under the 'emergency use' clause. Also, our body continues to evolve to fight attempts by external agents to inject foreign genetic material into our cells. Whether the same platform with work on future vaccines will be known only by performing science. But as always, data >> opinion.

You seem well read so you've already identified one of the key problems - the genetic code that forms the basis of the vaccine. Its not really my area, but from what I understand, dealing with synthetic RNA (RNA Mimics) is tricky since its never identical to cellular RNA. All of the associated problems will already be known to anyone working in that field, so there's nothing of value that I can add anyway.

I'm not sure what you are refering to, as the end proteins expressed by the ribosome should be the same, even if the syntetic mRNA is optimized for increased expression compared to the non-syntatic one.

At the same time the vaccines can't control which cells get the mRNA delivered as opposed to non-syntetic cells, where the cells are differentiated by their methylation and other epigenetics and gene expression control pathways, which I guess can be problematic for some cell types.

I don't think that is accurate. The spike protein that is being expressed has been modified (2p mutation) to enhance its stability. Proteins have a structure-function relationship and I believe this change in structure was done to inactivate the function of the spike protein, and merely use it as a immunogen.

But I was making a different point. Even before you get to the final expression of the protein, there are various steps that need to go smoothly. The mRNA sequence is carefully engineered to dodge the body's various defenses, among other things - and this sort of engineering is not trivial - which is the point I thought you were also making with - "and the hardest part of developing new mRNA vaccines is to research the genetic code to put in it. ".

But maybe I misunderstood your original point?

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