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Meet the Penn engineer who delivers mRNA inside human cells

Tom Avril, The Philadelphia Inquirer on

Published in Science & Technology News

Once inside the cell, they are taken up by cellular vessels called endosomes. The pH within these endosomes is more acidic. When the LNP becomes positively charged because of the acidic environment in those compartments, those now positively charged lipids will interact with negatively charged lipids inside, and essentially, it will disrupt that membrane, releasing the mRNA cargo inside the cell.

How do you make lipid nanoparticles?

Our lab uses a technique called microfluidics to make the LNP.

It’s a Y-shaped device on a chip. The fluid that flows through one side of the device is a mixture of four lipids dissolved in ethanol. On the other side is the RNA contained in an acidic citrate buffer. As the two fluids collide, they undergo a process known as chaotic mixing.

Because of the ionizable nature of the lipids, when they come into contact with acidic buffer, those lipids become charged. That charge mechanism then binds the RNA to the lipids.

That process is called self-assembly. It’s almost like an onion forming.

 

Were you at Penn when Drew Weissman and Katalin Karikó published their first findings on mRNA in 2005?

I was in high school back then. Unfortunately, I wasn’t there for that.

Before I got to Penn, in 2018, I was in Bob Langer’s lab at MIT as a research fellow. He’s one of the founders of Moderna. He’s considered kind of a father of the drug-delivery field.

Tell me about the study where you improved the efficiency of LNP.

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