monkeycantype 1 day ago

I remember from a few few years back that the lipid coating may have caused problems for the liver, when treating people for diseases that needed to target a lot of tissue, such as muscle disorders. Is that still the case?

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mike_hearn 13 hours ago

You remember correctly. Moderna had a lot of problems with their drug trials due to the lipid nanoparticles they were using to transport mRNA. They were toxic to the liver upon repeat dosings. Unfortunately, it appears they never found a fix for the problem. Instead they gave up and found a "business solution" by pivoting from drugs to the (at the time) less profitable vaccines, on the grounds that vaccines are something you only need to take once so the toxicity issue could be dodged. Doh. That was in 2017.

https://www.statnews.com/2017/01/10/moderna-trouble-mrna/

By the time COVID vaccines came around a few years later there was no evidence they had fixed the problems with lipid nanoparticle delivery. I looked for such evidence extensively at the time, for example, announcements by Moderna of breakthroughs or trials of new drugs. Today the situation seems not much different. Note that Moderna's wikipedia article has a section on "rare disease therapeutics" but it's literally empty:

https://en.wikipedia.org/wiki/Moderna#Rare_disease_therapeut...

Because of their failure to progress beyond COVID vaccines Moderna's share price got slaughtered, falling from a peak of ~$450 to ~$25 today.

I don't know if other companies were able to find breakthroughs here, after COVID I stopped following the topic. Unfortunately, although mRNA tech has great potential, when normal safety standards were reimposed it appears that Moderna went back to being unable to make anything safe enough to launch.

Jugurtha 12 hours ago

What was the success of other means, such as sugars and proteins? Something like glycocalyx or polysaccharide capsules? Or HIV like deployment gp41/gp120?

Gareth321 11 hours ago

> on the grounds that vaccines are something you only need to take once so the toxicity issue could be dodged

But we didn't take these vaccines once. We took many of them. Am I to understand a known side effect is liver toxicity for multiple doses?

popol12 11 hours ago

I guess the issue is not about taking the medicine once vs twice, but rather « a few times » vs « daily »

heavyset_go 24 minutes ago

Toxicity depends on dose. COVID vaccines just need micrograms of material to induce an immune response, I imagine it takes more than that to edit the genes of a large organ.

mike_hearn 11 hours ago

You have successfully read between the lines, yes.

Avamander 7 hours ago

They have not.

Balgair 21 hours ago

Unfortunately, I do not know. Sorry here.

If anyone else does know, please chime in!