Baby is healed with first personalized gene-editing treatment

> To accomplish that feat, the treatment is wrapped in fatty lipid molecules to protect it from degradation in the blood on its way to the liver, where the edit will be made. Inside the lipids are instructions that command the cells to produce an enzyme that edits the gene. They also carry a molecular GPS — CRISPR — which was altered to crawl along a person’s DNA until it finds the exact DNA letter that needs to be changed.

That is one of the most incredible things I have ever read.

One other fun part of gene editing in vivo is that we don't actually use GACU (T in DNA). It turns out that if you use Pseudouridine (Ψ) instead of uridine (U) then the body's immune system doesn't nearly alarm as much, as it doesn't really see that mRNA as quite so dangerous. But, the RNA -> Protein equipment will just make protiens it without any problems.

Which, yeah, that's a miraculous discovery. And it was well worth the 2023 Nobel in Medicine.

Like, the whole system for gene editing in vivo that we've developed is just crazy little discovery after crazy little discovery. It's all sooooo freakin' cool.

https://en.wikipedia.org/wiki/Pseudouridine

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?

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.

> 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?