[HN Gopher] What mRNA is good for, and what it maybe isn't ___________________________________________________________________ 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. ___________________________________________________________________ (page generated 2021-06-29 23:00 UTC)