a short history of gene expression editing
info
2022-09-11
This study from 2008 is the first one, of which i am aware, which finds, that
“nucleoside modification is an effective approach to enhance stability and translational capacity of mRNA while diminishing its immunogenicity in vivo”.
Which, in fair language, means the switch
U → m1ψ
is producing MOAR proteins than a natural mRNA AND evades the immune system longer. MUCH LONGER.
Let’s take a look.
illustration
1 - Firstly, they’ve played with it in vitro, adding some green fluorescent protein to test the expression and be funky.
How did they get the modified mRNA into the cell?
https://en.wikipedia.org/wiki/Lipofectamine
In order for a cell to express a transgene, the nucleic acid must reach the nucleus of the cell to begin transcription. However, the transfected genetic material may never reach the nucleus in the first place, instead being disrupted somewhere along the delivery process.[3] In dividing cells, the material may reach the nucleus by being trapped in the reassembling nuclear envelope following mitosis.[3] But also in non-dividing cells, research has shown that Lipofectamine improves the efficiency of transfection, which suggests that it additionally helps the transfected genetic material penetrate the intact nuclear envelope.[3]
Are we slowly getting to our Lipid Nanoparticles?
That worked great, it seems, the thing evaded immunity just perfect.
Anyway - who would need Interferon beta?
Interferon beta-1a (also interferon beta 1-alpha) is a cytokine in the interferon family used to treat multiple sclerosis (MS).[5] It is produced by mammalian cells, while interferon beta-1b is produced in modified E. coli.[6] Some research indicates that interferon injections may result in an 18–38% reduction in the rate of MS relapses.[7]
Interferon beta has not been shown to slow the advance of disability.[8][9][10][11] Interferons are not a cure for MS (there is no known cure); the claim is that interferons may slow the progress of the disease if started early and continued for the duration of the disease.[12]
2 - Then they proceeded to test this in vivo, using luciferase-encoding mRNA,
because, unlike other reporter enzymes (e.g., β-galactosidase, Renilla luciferase), no endogenous mammalian enzyme interferes with its detection
The results were innocent and very encouraging, no lightning activity in the lung, liver, heart, kidney or brainz… , so was the moment they decided to ignore everything but the spleen from now on.
Great stuff right here, i would be happy too were these my findings, perhaps, i would not kill all the lab mice 6 hours after i’ve had my way with them, just to take a look WHAT will be happening with the partially degraded mRNA which has been still detectable???
You might remember, some years later (2011), we’ve seen some popular science articles about eradicating diseases with gene editing, luminiscent mice and cats, smiling at us from the shiny pages of magazines. Isn’t she LOVELY?
They were promising a cure for AIDS, cancer, auto-immune diseases etc. Dr. Poeschla even got the Nobel prize for chemistry in 2008.
Some promising HIV research was done:
Gene deletion and complementation in Jurkat cells revealed that Sec24C facilitates infection and markedly enhances HIV-1 spreading infection. Downregulation of Sec24C in HeLa cells substantially reduced HIV-1 core stability and adversely affected reverse transcription, nuclear import and infectivity.
That’s it for now on the facts.
Link to slide for completeness
Now, we have a lab-bred virus, with GP120 HIV inserts, with 0,22% mortality. Whose good idea was to use this unproved technology on 70-80% of humanity?
Yes, the flu can reverse transcript, too. But what happens if you conjure up a little something here and change a little something there, so that it is impossible for the body to break down the slops?
What happens if the above plague consists of 45% waste mRNA?
This, for starters?
Have a great day everybody, keep asking questions!