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Baby is healed with first personalized gene-editing treatment

(www.nytimes.com)
1257 points jbredeche | 3 comments | 15 May 25 18:06 UTC | HN request time: 0.599s | source
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MrZander ◴[15 May 25 19:30 UTC] No.43998447[source]▶
> 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.

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Balgair ◴[15 May 25 20:31 UTC] No.43999018[source]▶
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

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monkeycantype ◴[15 May 25 22:30 UTC] No.44000029[source]▶
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 ◴[16 May 25 09:21 UTC] No.44003338[source]▶
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.

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Gareth321 ◴[16 May 25 11:29 UTC] No.44004070[source]▶
> 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?

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heavyset_go ◴[16 May 25 22:52 UTC] No.44010513[source]▶
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.
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mike_hearn ◴[17 May 25 19:37 UTC] No.44016445[source]▶
There have sadly been cases where the vaccines did perform unintended gene editing. It shows up as people whose bodies are still producing spike protein months or years after vaccination.
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floam ◴[17 May 25 22:08 UTC] No.44017374[source]▶
Are you saying that there are cases of longer than expected spike protein presence where these cases are actually because gene editing took place?
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mike_hearn ◴[18 May 25 08:16 UTC] No.44019816[source]▶
The Yale LISTEN study found such people for example. Studies on post vaccination heart damage also found free spike protein in the blood of those affected, i.e. the body had turned off the immune response to the spike due to persistent internal production. The most likely way this happened is understood if you dig into it.
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1. karagenit ◴[18 May 25 13:10 UTC] No.44021160[source]▶
Do you have a citation for this? The only relevant study I saw on the LISTEN website was a preprint of a study showing data on self-reported post-vaccine symptoms, but didn’t really talk about causes or gene edits (Krumholz et al. 2023).
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2. mike_hearn ◴[18 May 25 15:11 UTC] No.44021962[source]▶
It did discuss causes to some surface level: continuous spike protein production, T-cell exhaustion and Epstein-Barr reactivation. And they're investigating post-vaccine syndrome so the root cause there would be clear, as the study authors discussed in the LISTEN press release.

It's easy to find papers discussing the problem, just search Google Scholar. Example:

https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1002/prp...

Integration was proven in 2024, unfortunately :(

https://www.medrxiv.org/content/10.1101/2024.03.24.24304286v...

"Of the S1 positive post-vaccination patients, we demonstrated by liquid chromatography/ mass spectrometry that these CD16+ cells from post-vaccination patients from all 4 vaccine manufacturers contained S1, S1 mutant and S2 peptide sequences"

They can tell the difference between vaccine spike and virus spike as the vaccine spike was modified for stability. The exact pathway is speculated to have been DNA contamination due to manufacturing process defects. Sequencing of vaccine vials has shown far higher levels of DNA contamination than is considered safe, and the lipids would bring DNA into the cells just as well as they do mRNA making the safe levels much lower still.

https://osf.io/b9t7m_v1/download/

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3. bratwurst3000 ◴[18 May 25 16:15 UTC] No.44022412[source]▶
> A significant limitation of this study was the lack of approved testing to 100% rule out previous infection and it is possible the persistent S1 protein detected in the CD16+ monocytes of some of the patients in this study is from SARS-CoV-2 and not from the vaccine. There also exists the possibility that some of these new-onset symptoms post-COVID vaccination are unrelated to the vaccines. The data from this study also cannot make any inferences on epidemiology and prevalence for persistent post-vaccine symptoms. Thus, further studies and research need to be done to understand the risk factors, likelihood and prevalence of these symptoms.

https://www.medrxiv.org/content/10.1101/2024.03.24.24304286v...

But yes further study has to be made.