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What mRNA is good for, and what it maybe isn’t

blogs.sciencemag.org

11–20 of 152 posts

Re: What mRNA is good for, and what it maybe isn’t

#12
post #10

I am worried about the low level of intact mRNA in those vaccines, esp. as an IT guy. https://www.medicalnewstoday.com/articles/early-concerns-rai... 25-45% randomly modified or defective mRNA doesn't sound safe. It's a bit like machine code with random errors, isn't it?

RNA uses an error-correcting code, and if that fails all that should happen is that some of the proteins your ribosomes create will be misshapen. Your body is good at dealing with foreign proteins.

What error correction does RNA have? Are you just referring to the third base in the codons? DNA has some but I don't know of any for RNA, and it hardly seems worth it for most organisms to have RNA error-correction: it's better to just degrade the RNA and retranscribe it.

Re: What mRNA is good for, and what it maybe isn’t

#13

Derek Lowe's articles during covid have been a huge help trying to navigate the coronavirus hellscape we have been in. It's great to see him start to talk post-covid applications of medicine as things maybe wind down a bit. Delta+ willing

His "Things I Won’t Work With" articles are really informative and entertaining.

https://blogs.sciencemag.org/pipeline/archives/category/thin...

For example: Things I Won’t Work With: Dioxygen Difluoride https://blogs.sciencemag.org/pipeline/archives/2010/02/23/th...

Re: What mRNA is good for, and what it maybe isn’t

#15

Derek Lowe's articles during covid have been a huge help trying to navigate the coronavirus hellscape we have been in. It's great to see him start to talk post-covid applications of medicine as things maybe wind down a bit. Delta+ willing

We could retarget the mRNA batches tonight if it wasn't for the FDA not taking this seriously.

Re: What mRNA is good for, and what it maybe isn’t

#16
When it comes to the problem of targeting, one interesting and promising tech is photochemical internalisation [https://en.m.wikipedia.org/wiki/Photochemical_internalizatio...], where you put the mRNA inside photosensitive molecules (and not lipids) and then shine some light on the tissue/organ where you want the mRNA delivered. Where activated by the light, the molecules then enter the cells, dissolves and deliver the mRNA. The Norwegian company PCI Biotech has a tech they call fimaNAc for doing this with naked mRNA.

https://www.pcibiotech.no/nucleicacids

This presentation has a lot of illustrations and explanations:

https://www.pcibiotech.no/s/PCI-Biotech-SMi-RNA-Therapeutics...

Re: What mRNA is good for, and what it maybe isn’t

#17
post #16

When it comes to the problem of targeting, one interesting and promising tech is photochemical internalisation [ https://en.m.wikipedia.org/wiki/Photochemical_internalizatio... ], where you put the mRNA inside photosensitive molecules (and not lipids) and then shine some light on the tissue/organ where you want the mRNA delivered. Where activated by the light, the molecules then enter the cells, dissolves and deliver…

What happens to the unactivated mRNA in that case? I was under the impression that it was typically the actual use of the mRNA by the ribosomes that broke them down generally, but I could be off base there.

Re: What mRNA is good for, and what it maybe isn’t

#18
“The huge success of the mRNA vaccination platform”

Does anyone know what the agreed upon criteria for asserting the success of mRNA vaccinations is?

Aren’t we anticipating an uptick in cases in the US as we approach winter? Why are we assuming success already?

Re: What mRNA is good for, and what it maybe isn’t

#19
post #16

When it comes to the problem of targeting, one interesting and promising tech is photochemical internalisation [ https://en.m.wikipedia.org/wiki/Photochemical_internalizatio... ], where you put the mRNA inside photosensitive molecules (and not lipids) and then shine some light on the tissue/organ where you want the mRNA delivered. Where activated by the light, the molecules then enter the cells, dissolves and deliver…

What happens to the unactivated mRNA in that case? I was under the impression that it was typically the actual use of the mRNA by the ribosomes that broke them down generally, but I could be off base there.

The same mRNA can be used by multiple ribosomes. More info and "photos": https://biology.stackexchange.com/questions/54752/can-mrna-b...

Re: What mRNA is good for, and what it maybe isn’t

#20

I wrote a long essay about the same topic and came to similar conclusions as Derek Lowe: https://trevorklee.com/are-mrna-therapies-the-future-of-phar... One thing that I'd like to emphasize is how unbelievably tiny mRNA therapeutics have to be. It's probably around 30 mg, and it's hard to do it more than once every few weeks, at least judging by siRNA therapeutics (which have similar immune issues). 30 mg is really t…

> 30 mg is really tiny

Not really. For example the amount of beta blocker I take for my heart problems is 5mg per day - the pill size goes down to 2.5mg.

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