[HN Gopher] What mRNA is good for, and what it maybe isn't
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What mRNA is good for, and what it maybe isn't
Author : jseliger
Score : 79 points
Date : 2021-06-29 20:38 UTC (2 hours ago)
(HTM) web link (blogs.sciencemag.org)
(TXT) w3m dump (blogs.sciencemag.org)
| espenwa wrote:
| When it comes to the problem of targeting, one interesting and
| promising tech is photochemical internalisation [https://en.m.wik
| ipedia.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
| https://www.pcibiotech.no/s/PCI-Biotech-SMi-RNA-Therapeutics...
| lazyjones wrote:
| 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?
| wahern wrote:
| What's the replication accuracy of SARS-CoV-2?
| nabla9 wrote:
| That's why there are clinical trials. Humans testing to find
| out what happens.
|
| All mRNA disappears from body in few days anyway.
| pjscott wrote:
| 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.
| tgb wrote:
| 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.
| anonymouse008 wrote:
| One of the most amazing talks on OOP was Alan Kay linking the
| approach to biology.
|
| I had just gotten into Swift and started loving on
| NotificationCenter - so when he spoke to how messages fly
| around programs like hormones and proteins in the body,
| transferring states, it was an Ah ha! I finally realized why I
| loved (and misused) Notifications.
|
| Then this whole mRNA vaccine came about -- and I remembered the
| absolute terror and anxiety of my dealings with unknown
| Notification Center errors and how little can be correlated
| because the debugger doesn't really trace down where said
| object who is screwing up some UI got the notification from --
| I had 1000s of objects all screaming messages in house of
| electrons... thankfully no ones body was on the line.
|
| Now I'm not saying I'm anywhere near a biologist or PhD
| virologist... but we sure are learning more about the body's
| mechanics each day, and it's not that far of a stretch for us
| to say there may be some latent or unindented effect of having
| a spike protein (either properly transcribed or not) flying
| around knocking into objects with open handlers.
| amelius wrote:
| > So if you're going to give patients an mRNA injection and you
| don't want to set off alarm bells in the innate immune system,
| you're going to have to carefully engineer your sequences at the
| very least.
|
| Isn't that what substituting uracil by pseudouridine solves?
| klevertree wrote:
| No, that substitution helps, but it doesn't solve the problem.
| You're still introducing foreign mRNA into the body, and the
| body still has millions of years of evolution telling it that
| foreign mRNA = invader .
| klevertree wrote:
| 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 tiny. It's hard to come up with a meaningful
| therapeutic in such a small amount of material. People have been
| hyping up self-replicating mRNA as a solution, but that's still
| in its infancy, and has its own problems regarding the
| "compilers"/polymerases that need to be packaged with it.
| readams wrote:
| Worth noting that even if it's good for literally only infectious
| disease vaccines, we're still taking about an enormous
| breakthrough with the potential to save hundreds of millions of
| lives. Imagine vaccines for malaria, HIV, Zika, and many others.
| InTheArena wrote:
| 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_
| sjg007 wrote:
| Delta+ and the next variant after that just in time for school
| in the Fall and a bunch of unvaccinated kids.
| nabla9 wrote:
| 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...
| wbl wrote:
| We could retarget the mRNA batches tonight if it wasn't for the
| FDA not taking this seriously.
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