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Comment by passivate | Hacker News Reader

>While it wasn't that hard, general public does not know where to even look for primary or even preliminary evidence. Much less how to evaluate the densely written papers.

I feel like its much worse than that. All of current research is very specialized. I am not a scientist but I do work in vaccines. After having worked for the past eight years in this field, I feel I can generally get the gist of scientific articles/papers, and understand if its something useful or junk - but only in my niche areas. Outside of that, I'm pretty much your average Joe.

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The same could be said about the science behind lockdowns (as very little was knows about the effects of attempting to control a pandemic until this incredibly costly experiment went underway), but it doesn't stop experts proclaiming this is what is needed to help.

Vaccines (especially mRNA vaccines) are not a bad field to be an expert in.

As an example I have chronic sinusitis without polyps which totally destroys my quality of life, while I can probably live with it for a long time. I’m looking at the successful cystic fibrosis inhaled vaccine trials that looks like a great way to help the cells produce missing proteins.

I’m hoping for similar treatments to be available in the near future, and I have some money that I would happily use to invest / donate in a chronic sinusitis vaccine development, but so far I see only biologics trials that are probably much slower to go through because of the greater toxicity.

Actually your knowledge is enough for you to have an edge over other people in investing in biotech companies.

The problem with the medical world vs people who suffer from chronic illnesses is even the doctors who treat them don't seem to understand how bad it is to live with.

Last time I saw my ENT doctor he's like well it's not that bad and I just wanted to scream at him.

I liked how someone else on HN put it: your body is constantly sending an error code but there's no way to shut it off.

Do you also have chronically irritated, dry sinuses with no polyps?

I've tried nasal irrigation and a corticosteroid but nothing works.

Yes. My symptoms correlate with the amount of air pollution around me, and much worse in winter.

Right now the only thing I can do is travel away from Europe to south/central america for the winter.

I tried all commercial air cleaners, but they don't decrease toxic gases, just PM2.5, which doesn't help me. I'm thinking of building a house/apartment with very clean air (maybe using nitrogene and oxygene concentrator). Also I'm planning to try cortisosteroid in my sinuses using a biodegradable net.

Biologics may help as well, but they help only IL-4 / IL-5 type inflammation, and I don't know what cytokins are causing my inflammation (I was thinking of doing an cytokin profiling from biopsy, but of course I need a great ENT doctor to help with it).

At the end the main problem is that there are multiple causes with CRS symptoms, so it's impossible to have 1 drug to cure all the symptoms. Also as it's not deadly short term, FDA is much stricter with the drug companies that try to come up with treatments, which is understandable.

Well vaccines as a field is super-mega broad, there are so many pure research sub-disciplines one can choose to be an expert on due to the intersection of medicine/immunology/chemistry/biology. And even those are super broad themselves. From an applied sciences standpoint again there are various disciplines depending on the particular vaccine technology - fermentation, protein purification, conjugation chemistry, formulation, drug delivery, etc, etc, etc. From an analytical chemistry/biology standpoint there are dozens more fields that come into the picture when testing. You can spend years and decades in any of these niche fields and still not probe the depths of our accumulated knowledge. And once you have a product, you get into the regulatory domain - finding the quickest and shortest path to the market - which is its own nightmare.

I don't know much about the particulars of the vaccine you are referring to, but when it comes to investing, I think it is always safe to assume that all major investing firms have ready access to SMEs that can give them the scoop on any company they're interested in.

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.

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?

I had sinusitis that left me bedridden for a week once. You have my sympathies.

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