Making medicines in chicken's eggs
Many very important drugs, including anti-cancer and diabetes therapies, contain very large, complex proteins that are extremely difficult to make without using living cells. But this is expensive, and can make the products harder to purify. Now, scientists at the Roslin Institute at the University of Edinburgh have genetically modified chickens so they package up the desired proteins - in very large amounts - in the albumen - or the whites - of their eggs. Georgia Mills heard how it works from Lissa Herron, head of the Eggcellent Proteins Business unit at Roslin Technologies...
Lissa - The great thing about chickens. Well there's many great things about chickens actually. So one thing is that chickens are very evolutionarily different from mammals. And what that means is you can make proteins for mammals that will have no effect in the chicken at all. Another is that the complex pattern of sugars that need to get attached to the protein for some proteins to be active. The chickens actually do it in a way that's very similar to humans. And then the final main reason is that large scale chicken production for eggs, and then the separating of egg whites from egg yolk and cracking the eggs in everything, is already very scalable. There's already large scale production both in the food industry and in the pharma industry for production of vaccines and eggs. So we can put all these things together and have something that's really scalable very quickly.
Georgia - So you're getting chickens to basically lay eggs with specific proteins in. How have you done this?
Lissa - We used a lentivirus, which is a particular type of virus that can insert DNA into the genome of an organism. That virus was modified so that it can't replicate - all it can do is insert the gene. And we also had another bit of DNA called a promoter and that tells the gene when and where to express the protein. And so we made one that very specifically and very efficiently tells the chicken "express this protein only in egg white in a very large quantity".
Georgia - How then do you get the protein out of the egg?
Lissa - We crack the egg; separate out the egg white from the rest of the egg components, and then we use a technique called chromatography, which is how everyone separates proteins from each other in a mixture. And what we found is that we can actually use basically the identical kinds of methods that people use for purifying proteins from cells.
Georgia - How much can you get out of a single egg?
Lissa - It depends on the particular chicken line that we're talking about. But in our best expressing line we can get between one point five and three grams per litre of egg white. So, and for the particular protein that we're talking about, a single egg can give us a dose for an adult. Very easily scalable, so you can have it be a single chicken or you can have it be thousands of chickens relatively quickly.
Georgia - What is the effect if any on the chickens?
Lissa - The chickens can't tell. As I say, we were very careful to choose proteins that don't have an effect on the chicken, and because the gene is there from the start, as far as the chicken is aware it's just another egg white protein. So it sees it as a "self" protein and doesn't have an immune response against it. And the modification is made only once. At that point we just breed forward for the next generation. So our interferon chickens, for example, are on something like the seventh or eighth generation.
Georgia - What about the eggs. Could you eat the eggs?
Lissa - You can't eat the eggs because they're from a genetically modified organism. And the regulations say you can't do that if you did accidentally eat an egg. For some reason it's unlikely to have any effect on you because the proteins won't survive your stomach. But the proteins are not intended for eating!
Georgia - Okay. Good to know! Okay. So what's next and now you've shown that this can be done in ways that you think can be scalable to industry, what's the next step?
Lissa - So now this project has moved out of the Roslin Institute and into Roslin Technologies, which is a company. And, initially, we're going to be marketing these proteins as research reagents so that researchers, these proteins are used widely in research and our hope is that researchers will will buy these and use them; and that will help validate our claims and people can confirm that the proteins are what we say they are. In the meantime we'll be developing - we have a particular interest in - animal health, as we've come out of an animal health institute. And also we're interested in speaking to people who would be interested in developing human or animal therapeutics.
Georgia - Are there any disadvantages to using the chickens?
Lissa - Yeah. There's always a risk. You know even though we'd have very high spec facilities that have very high biosecurity controls, it is a living organism, so you could always get an infection. But that's something that happens with mammalian cell culture as well - you know you can get infections into in the cell culture tanks. Obviously, you know, some people are not keen on using animals as a tool in general. And it does take a while to get the chickens made - takes about a year to get to a point where you have hens laying eggs...