The Bountiful Benefits of mRNA   Thanks, COVID!

By Shlomo Maital

Prof. Kathryn Whitehead, Carnegie-Mellon U.

   There are things in this world that are bad – like, really really bad – that brings bountiful benefits.

    Take, for instance, COVID.


     Well, yes. It brought us mRNA vaccine technology. In just  11  months, mRNA vaccines were developed, tested and implemented.  Saving countless lives. And that technology may be used in future to teach our bodies’ immune systems to fight cancer, Ebola, and other nasty illnesses.

      But how does mRNA work?  A brilliant TED talk by Prof. Kathryn Whitehead, a drug-delivery scientist from Carnegie Mellon U. in Pittsburgh, explains it. I am awed by how clearly, she describes this complex technology.

      Want to know how that mRNA vaccine you got works?   Here is Prof. Whitehead’s explanation, given in a brilliant TED talk recently.

   The Magic:  when messenger RNA (mRNA) enters the cells in our body, the mRNA acts like an instruction manual, that tells our cells to make a foreign protein, in this case, the coronavirus spike protein.  When our immune cells see the spike protein, they rush to protect us from it, and they teach themselves to remember it. Presto! ….so that they can kill it if it ever returns.

   The Problem:   When mRNA is administered   it’s injected into our muscles or our blood stream,  but we actually need it to go inside of our cells.     

    Unfortunately, mRNA is fragile, and our bodies will destroy it before it goes very far.You can think of mRNA like a glass vase that you’d like to send in the mail without a box and bubble wrap. It’ll break long before it’s been delivered. And without an address on the box, your postal delivery service will have no idea where to take it.  And so if we’re going to use mRNA as a therapeutic,  it needs our help.

  The Struggle:    For over five decades, scientists and engineers like myself have been creating the shipping materials for nucleic acid drugs, like DNA and RNA.  Through trial and error, we’ve created packages that deliver intact vases to the wrong address; that delivered to the right address but with a broken vase; packages that get ripped apart by attacking dogs; and packages that throw out the mail carrier’s back.  It’s taken many years to get the science right.

   The Solution:   Fat!  Yes, fat cells!  In fact:  cholesterol.  The stuff we are warned about, that clogs our arteries? 

     Prof. Whitehead continues:  Deliver the mRNA package in tiny balls of fat that we call lipid nanoparticles.  Let me tell you what they are and how they work. So first of all, “nano” just means really, really small. Think of how small a person is compared to the diameter of the earth.  That’s how small a nanoparticle is compared to the person.  These nanoparticles are made up of several fatty molecules called lipids.

      Fat is an awesome packing material — nice and bouncy.  Interestingly, our cells are also surrounded by fat to keep them flexible and protected. Years ago, scientists had the idea to create lipid nanoparticles that would act like a Trojan horse.  Because the lipids in the nanoparticle look similar  to the membranes that surround our cells,  the cells are willing to bring the nanoparticle inside,  and that’s when the mRNA is released into the cell.

     It turns out that while cholesterol can be bad when it’s in our bloodstream, it’s actually a really good thing for our cell membranes.  Cholesterol is a stiff molecule that wedges itself in between the other lipids in the nanoparticle to fill in the gaps and hold them all together.  It provides structural support so the nanoparticles don’t fall apart in between the injection and when they get into our cells.

   Finally, one more ingredient.  This one is a polymer called polyethylene glycol. So let’s call it PEG. That’s much easier.  PEG is a water-loving molecule. So it surrounds the lipid nanoparticle and it holds it all together — the bubble wrap for the mRNA.


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   My own take:   It took many scientists many, many years of hard work and long hours to perfect the lipid nano ‘delivery’ molecule – just in time for  Pfizer and Moderna to save the world.

    Those scientists deserve the Nobel for Medicine – just today awarded to a Swedish scientist, who sequenced the DNA of Neanderthal Man. 

     A brilliant feat!  But – compared to what Prof. Whitehead described? The Swedish Academy is detached from reality.