How new mRNA vaccine technology battles COVID-19 | Interview with Dr. Robert Langer

0:00:18.2Delivery to the cells

Jed Macosko: Hi, this is Dr. Jed Macosko at Wake Forest University and at Academic Influence. And today, I have an old friend visiting with me today, Professor Bob Langer from MIT.

And Professor Langer has done so many different things over his long career, but what I want you to know about today, Professor Langer, is how have you helped develop the vaccine for COVID that we are all super excited about?

Robert Langer: Well, I don’t wanna give myself... Moderna, which is a company I co-founded is the one that developed the vaccine and of course other companies like Pfizer and BioNTech and CureVac are also doing that.

But just to go back, early in my career, one of the first things that I was involved in was developing what are called drug delivery systems. And we published a paper in Nature, for example, in 1976, which was the first time people were able to take macromolecules including nucleic acids of which mRNA is an example, and put them in little tiny particles and show that they could be useful for delivery, for drug delivery.

So that actually, and then after that paper, we’ve spent probably the last 45 years publishing lots of other papers, maybe something like 1500 papers and a lot of patents too really explaining and understanding how you can do this and developing new materials, new lipids, different principles, and actually applying them to different medical problems.

So Moderna, myself and several other people started it in 2010, and then it was really just beginning, just an idea, but over the last 10 years, now there’s 1000 people in it, and they’ve actually got something like 14 products in clinical trials.

The vaccine, the COVID vaccine, is actually not the number nine vaccine that Moderna has been developing, but it’s moved incredibly fast in part because of the urgency that’s occurred with people dying. And now that vaccine... Actually, today is the 17th of December, and this is the day that the FDA is reviewing it to give emergency approval.

And I’m certainly optimistic that it will receive that because the data has been very, very good, and it will also help hopefully a great, great, many people and hopefully help get the world back to normal at some point. But at any rate, just going back to the science, if you took messenger RNA, which is the key ingredient here, and just gave it to the patient themselves, it wouldn’t work. It would basically get destroyed right away.

And so what is done is the Moderna scientists have also taken tiny particles, in this case made of special lipids, put the messenger RNA in it, and then when you inject it in the body, it’s now protected. It can go into the cells, and it will make the vaccine.

And actually, every mRNA vaccine, whether it’s Moderna or Pfizer or BioNTech or CureVac or Translate Bio, they all need these little particles to protect the messenger RNA and to get it to work.

0:03:37.6How the vaccine was developed so quickly

Jed: And tell us why mRNA vaccines had a leg up on traditional vaccines for the COVID vaccine? Was it that they could be developed more quickly or why did they all come in earlier than the other vaccines?

Robert: Yes. Well, see, traditionally, vaccines take many, many years to develop. One of the reasons they take many years to develop is they’re using what are called attenuated viruses or killed viruses or you have eggs and you have to grow them for a year to make enough.

But here with messenger RNA... And by the way, I should also say, you may need a giant building and factory to do all this, and it takes a long time. The beauty of messenger RNA is there’s a central dogma: The DNA makes RNA makes protein. So the protein, of course, is the key, but if you make the messenger RNA and give that to the patient, the patient actually is the factory.

So you give the messenger RNA, you inject it into the patient, and the patient does what all those factories are doing for making a protein. And so the body is the factory, and you can make the messenger RNA in literally several weeks, maybe five weeks, and that’s what Moderna did. BioNTech also did it.

Jed: Do you think that with every new vaccine moving forward from COVID on, mRNA will probably be the most likely route that those vaccines take?

Robert: Well, I’m prejudiced. I don’t wanna say that it’s always gonna be a likely route, but it’ll certainly, I think, become a major way of making vaccines. I think certainly, the future of it is very, very important, so I think it’ll certainly be used to make a lot of vaccines.

0:05:21.2What’s the difference?

Jed: Now, one question that I have that I’ve been wondering for a long time and you might know the answer, why does Pfizer and Moderna have the same technology, but they have to be stored at different temperatures?

Robert: Right. Well, that relates to two different things. One is the messenger RNAs themselves could be slightly different because they’re modified, but probably the key is the nanoparticles. If you’re making nanoparticles out of things like lipids and you try to store them, there could be issues of phase separation and instability.

So the lipid nanoparticles are made differently in both cases or different ingredients in each case. Some are the same ingredients, but others are different ingredients. And so either because the messenger RNAs are slightly different or because the nanoparticles are slightly different, but that’s the reason.

Jed: So are you excited about this big FDA meeting today that’s gonna go down and hopefully lead to many more people getting the vaccine here in the United States and elsewhere?

Robert: I am. I mean, it’s the culmination of an enormous amount of work that really outstanding scientists at Moderna including a number of graduates from our lab have worked on and so... But I just think it can do so much good for the world, and so today is certainly an important day for that.

0:06:39.4Sign off

Jed: We are so glad to have had a little bit of time with you on this momentous day and to hear a little bit about how your technology works. We really appreciate you being on the show and being an influential engineer that really inspires other people, young people, to become engineers too.

Robert: Thank you so much. It’s been an honor and a pleasure and great to see you again.