Lipid nanoparticles, Moderna, and everything
This bit isn’t quite current, as it’s an article about Moderna from 2017. Interesting company to say the least and worth a read, though! Mostly about the business, but contains this gem:
“The choice to prioritize vaccines came as a disappointment to many in the company, according to a former manager. The plan had been to radically disrupt the biotech industry, the manager said, so “why would you start with a clinical program that has very limited upside and lots of competition?”
The answer could be the challenge of ensuring drug safety, outsiders said.
Delivery — actually getting RNA into cells — has long bedeviled the whole field. On their own, RNA molecules have a hard time reaching their targets. They work better if they’re wrapped up in a delivery mechanism, such as nanoparticles made of lipids. But those nanoparticles can lead to dangerous side effects, especially if a patient has to take repeated doses over months or years.
Novartis abandoned the related realm of RNA interference over concerns about toxicity, as did Merck and Roche.”
Has anyone heard ANYONE mention this in conjunction with the vaccines, especially in light of the perpetual booster plan? Anybody? The vaccine companies, CDC, FDA, public health officers? Cos I haven’t heard a word on the subject from any of them. Possibly I wasn’t paying attention. Or maybe I was. Input appreciated.
This is current & explosive:
Also of interest,
“Moderna 1.0, and life in the caves, came to a close in 2013, according to company lore.
That’s when Moderna — which had just 25 employees — signed a staggering $240 million partnership with UK pharmaceutical giant AstraZeneca. It was the most money pharma had ever spent on drugs that had not yet been tested in humans.
The agreement is commemorated in one of Moderna’s offices by a framed clipping from the New York Times. Page B7 of the March 21, 2013 edition: “AstraZeneca Makes a Bet On an Untested Technique.”
For AstraZeneca, the unprecedented deal came at a time of uncertainty. A series of clinical failures had led the firm to fire its head of research and lay off 1,600 scientists. Pascal Soriot, just six months into his tenure as CEO, was under pressure from investors to chart a new course. And Moderna, with its brash ambition to bring 100 drugs to clinical trials within a decade, gave Soriot a way forward.
The rich deal started a gold rush for Moderna. Everyone, it seemed, wanted in.”
Also interesting from the article,
“‘I would say that mRNA is better suited for diseases where treatment for short duration is sufficiently curative, so the toxicities caused by delivery materials are less likely to occur,’ said Katalin Karikó, a pioneer in the field who serves as a vice president at BioNTech.
That makes vaccines the lowest hanging fruit in mRNA, said Franz-Werner Haas, CureVac’s chief corporate officer. ‘From our point of view, it’s obvious why [Moderna] started there,’ he said.”
To summarize: So, we know this mRNA gene therapy is toxic, therefore, we must only treat diseases in which the “patients” are exposed to our toxic sludge for a short amount of time. Oh, I got an idea, lets inject the toxins into people, because the toxins will be short lived, duh!!!????
And of course, the booster shots will only be what? two to four times a year? No problem….
Riddle me this, as well. How could Moderna have the first vaccine done in two days, but couldn’t whip up one against Delta over the week-end? Or even the past several months?
Read Whitney Webb’s three part deep dive investigative reporting into Moderna.
Well, it does. But go ahead and take the first generation jab anyway.. and maybe a booster or two also just because. We’ll eventually figure out how to apply this mRNA tech without it getting into your ovaries, etc.
Title: Novel lipid nanoparticle provides potent SARS-CoV-2 mRNA vaccine at low dose with low local reactogenicity, high thermostability and limited systemic biodistribution
Abstract: Concerns with current mRNA Lipid Nanoparticle (LNP) systems include dose-limiting reactogenicity, adverse events that may be partly due to systemic off target expression of the immunogen, and a very limited understanding of the mechanisms responsible for the frozen storage requirement. We applied a new rational design process to identify a novel multiprotic ionizable lipid, called C24, as the key component of the mRNA LNP delivery system. We show that the resulting C24 LNP has a multistage protonation behavior resulting in greater endosomal protonation and greater translation of an mRNA-encoded luciferase reporter after intramuscular (IM) administration compared to the standard reference MC3 LNP. Off-target expression in liver after IM administration was reduced 6 fold for the C24 LNP compared to MC3. Neutralizing titers in immunogenicity studies delivering a nucleoside-modified mRNA encoding for the diproline stabilized spike protein immunogen were 10 fold higher for the C24 LNP versus MC3, and protection against viral challenge in a SARS-CoV-2 mouse model occurred at a very low 0.25 µg prime/boost dose of the same immunogen in the C24 LNP. Injection site inflammation was notably reduced for C24 compared to MC3. In addition, we found the C24 LNP to be entirely stable in bioactivity and mRNA integrity when stored at 4 ºC for at least 19 days. Storage at higher temperatures reduced both bioactivity and mRNA integrity, but less so for C24 than MC3, and in a manner consistent with the phosphodiester transesterification reaction mechanism of mRNA cleavage. The higher potency, lower injection site inflammation, and higher stability of the C24 LNP present important advancements in the evolution mRNA vaccine delivery.