Moderna

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Hmm.   This pandemic has afforded us a brand new method of immunizing our populations, making the disease difficult to take hold.  Consider that in 2020, we were being overrun with COVID-19.   And, then, POOF!  Vaccines appeared on the horizon.

AstraZeneca and J&J

Sure, we had the standard types.  (Not really.)   AstraZeneca and Jannsen (Johnson & Johnson) quickly found a way to get the virus components linked to a viral vector.  And the Jannsen version was a single shot approach while the AstraZeneca needed two inoculations.  Except…

These two versions had side-effects that rendered them less of use.   (Not to mention that J&J decided to let an unproven venture in Baltimore produce its product and AstraZeneca screwed up its clinical trials.)  And, lo and behold, Emergent Biosolutions (J&J’s contract manufacturer) was shut down by the FDA.  For contamination issues, for documentation issues.   (Note that non-US suppliers of the vaccine were able to proceed- but they didn’t really supply the US market.)

But two companies- teensy little firms- came up with a most novel approach.  Instead of using attenuated virus vectors, they added viral components to messenger RNA (mRNA).   These capitalize on the discovery of the unique features of the target virus that can trigger our immune system.  Attaching these components to messenger RNA and then injecting them into our body means we now possess the instructions to activate our immune system.  We can use the mRNA strands to produce the antibody proteins that will attack the target (i.e., set off our immune system).  These instructions are then stored and will be ready for use when the real virus enters our body.  In essence, we have converted our own cells into microscopic factories producing the vaccine against the target.

Which two teensy companies?   BioNTech in Germany and Moderna here in the USA.  Neither of these two firms would be able to ramp up production to satisfy the need for the billions of humans who will need to develop immunity.  BioNTech cut a deal with Pfizer, one of the larger pharmaceutical firms out there.   Moderna partnered with Lonza Group AG (worldwide venture) and Catalent (Indiana), which are pharmaceutical suppliers (entities that don’t market drugs to the world, but produces them for big- and little- pharma). [Moderna has since added more partners such as Sanofi, Samsung, and Thermo Fisher Scientific to satisfy the world-wide demand.]   And, critically, Moderna produces the nanoparticles and the mRNA components (the components of the vaccine)  in a factory [more like a molecular biology lab] that used to be part of Polaroid [the plant is in Norwood, MA], which are then shipped to the vaccine producing entities.

Given the success of this COVID-19 venture, the use of mRNA is about to expand.  At the very least, Moderna plans to develop products to eradicate Zika and Nipah (emerging virus vectors), cytomegalovirus, Epstein-Barr virus, as well as the flu.   (After all, the COVID vaccine will no longer be a big money-maker within two years; the firm needs products to keep up its revenue stream.)  Moderna actually has 10 virus vaccines that are in or soon to be in human trials.   It hopes to add HIV to their trials.

These new vaccines won’t have a fast-track method for approval (as was afforded the COVID-19 vaccines), so the process will be much longer, but they do have shorter lead times to develop- which is why Moderna has high hopes for its flu vaccine, which should have better efficacy rates than the egg-based vaccines we’ve been using forever.

The key point is the mRNA is a modular technology.   Sure, they deliver the genetic code for our body’s reactions- but it’s our cells that do all the hard work.

mRNA is normally attacked and destroyed by our bodies when so confronted.   It took the research of Drs. K Kariko and D Weissman (University of Pennsylvania) to find a way around the body’s immune system.  This development has been licensed by the mRNA technology firms to allow their products to work.  (Note: Dr. Kariko joined BioNTech way back in 2013).

Even so, the body’s enzymes can break down the mRNA.  Moderna uses lipid nanoparticles (ones that don’t accumulate in our livers) to surround the mRNA, in essence protecting the mRNA from the enzyme attack.  They are looking for new nanoparticles (or variations of the ones they are using) so that the stringent temperature conditions for storage (-80 F) can be obviated.

Dr. Robert Langer

But, most of you don’t know that Moderna was created by a fellow MIT ChemE grad.  Back in 2010.   The ubiquitous Bob Langer, with two others.  They were funded by Flagship Pioneering (a venture capital firm headed by Noubar Afeyan, also a Biochemical Engineer) to found LS18 (now called Moderna) in Cambridge, Massachusetts.  [Flagship made a fortune when Moderna went public and still retains about 18% of the firm.] Bob’s original idea was to reprogram human fibroblast cells into pluripotent stem cells using mRNA, long since abandoned as a strategy.  Moderna’s secured its fate by hiring its second employee, Stephane Bancel (pilched from BioMérieux SA), now the firm’s CEO.

Kind of like “the rest of the story”.

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10 thoughts on “Moderna”

  1. Roy —

    Good article.

    How about kudos for the “fast-track” approval which also proves (to me) that our FDA approval system needs work. Taking 3-6 years to complete trials and certification for a new drug should be unacceptable. I am sure a lot of what is currently taking so long could be interpolated via computer models and more sophisticated testing.

    What do you think? Possible? Likely?

    1. The ‘fast track’ approval is only meant for emergency situations, where decisions are made that could let some safeguards be skipped- since the alternative (imminent death and grave illness) is unacceptable. I’m not sure I’d like that process used for general drug approval.

  2. For some reason, I never realized that Moderna was small (as pharma companies go). I hope they are able to keep going with this technology because, without it, I shudder to think of what might have happened if we hadn’t developed a vaccine for COVID. And, these terrible viruses seem to be popping up more and more. I know a person who has been living with HIV for years and he takes an extensive cocktail of medication every day. A HIV vaccine would be wonderful.
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