Science & Technology



Meet the Penn engineer who delivers mRNA inside human cells

Tom Avril, The Philadelphia Inquirer on

Published in Science & Technology News

We made a library of variations with different lipids to find a blend of potent delivery to the lungs, but balanced with low toxicity. You want it to be safe.

We tagged the different kinds of lipid nanoparticles with a bar code of DNA, so we could identify them using next-gen sequencing technology. We can essentially count the number of LNP delivered to specific parts of the body by using those bar codes.

So we could figure out which one was the best out of the pool. We can really iterate and evolve a better technology much more quickly.

Was there one that was the clear winner?

We started out with 180 LNPs. You test those in cells first, because if something doesn’t work in a cell, it’s not worth testing in an animal.

We had 96 that were promising, then ultimately, we identified four very promising formulations. For targeting the lungs, the best was one called CAD9, which stands for cationic degradable lipid.

There was no LNP delivery to the liver whatsoever. The mRNA only was delivered into the lungs, which is amazing.


Especially for a cancer application, you might not want those therapeutics going into healthy organs where there’s no tumor. This one is very much focused on the lung.

How about getting into the brain?

The brain is very challenging, because you have to cross the blood-brain barrier.

My postdoc was basically able to create a model of the blood-brain barrier on a chip. We developed a type LNP that could cross that barrier on the chip.

We’re not at a therapeutic point yet. This is just a fundamental chemistry proof of concept. But we think this is something to build off of that is very exciting.

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