A relatively new ‘DNA cut-and-paste technology’ with unprecedented precision and virtually infinite possibilities. CRISPR-Cas is the subject of Sjaak Philipsen’s lunch lecture on 31 October. Philipsen is professor of the Genomics of Cell Differentiation. EM interviewed him prior to the lecture, asking six questions about the technology that is revolutionising medical science.

What is CRISPR-Cas?

“Briefly put, they are snippets taken from the immune system of a bacterium that we have extracted and now are transplanting in a mammalian cell. One of these components, the Cas9 enzymes can be placed with great precision in recognition sites in the DNA, and then we can snip out this part of the DNA. In this way, we can quickly and easily deactivate genes or even add another DNA sequence to replace the part that has been cut out. In other words: introduce a mutation. This technique makes it possible to repair hereditary genetic deviations in human embryos. That is really something quite extraordinary.”

Science published an article about this in 2013. Why is it a hot topic now?

“You have to understand that in terms of science, 2013 is very recent. It often takes a long time before a technology is usable. But CRISPR-Cas has turned out to be very successful and simple to use in any lab. You could say that this process actually was very rapid. The applications have even advanced to the stage where we can repair and mutate genes in human embryos.”

It sounds fairly simple. Could I also use it to tinker with DNA?

“Actually, you could. Provided you have the basic skills needed to cultivate cells and insert enzymes and molecules into them. But that can be done in any molecular biology lab. It would be more of a challenge doing it on the kitchen table, but theoretically, it’s possible. But you don’t have to take that route. In the United States, you can order CRISPR kits to modify bacteria and yeasts at home. That’s amusing, but it wouldn’t be allowed here.”

What possibilities does CRISPR-Cas offer?

“There’ a huge range of new possibilities. You can introduce multiple modifications simultaneously in a single cell. And the process has gotten much easier and faster. Another interesting aspect – for beer brewers, for example – is you can give yeast specific attributes. Yeast could be modified to produce more alcohol, for example. Or you can deactivate the gene in the potato plant that makes it vulnerable to Phytophtera mold. This significantly increases the chance of a successful harvest.”

How are you using the technology?

“I study the functions of genes. Until recently, we often used mice for this, endlessly selecting and breeding them. That was a process that took years, and the cells of a mouse are not the same as the cells of a human being. There are also ethical objections to working with laboratory animals. But now I can very quickly modify genes in cultivated human cells and immediately see the effect. Keep in mind that to extend this to clinical trials, animal testing will still be necessary. You can’t just proceed directly from a tissue culture plate to a human patient.”

“Thinking back now, I’m a little embarrassed, because I waited three months after the first publications before ordering the CRISPR-Cas components. For less than 100 euro you have all the equipment and information you need delivered to your door within a week. I thought all the possibilities this technology was claiming were almost too good to be true. The fact that it’s easy to obtain this product through an American non-profit organisation has contributed a great deal to the widespread use of this technology.”

Are there any ethical dilemmas?

“There are definitely ethical questions we need to ask. As long as we are working with cultivated cells, there isn’t really an issue. But we can now correct hereditary illnesses in human embryos. This has already been proven to work. Working in a lab with embryos that have not been used following an IVF treatment isn’t too problematic. But theoretically, these embryos could be placed back in the uterus. Is that wise? The question is when and if you should take that next step…Technology is advancing at an incredible pace that the ethical discussion is always trying to catch up.”

 

The CRISPR-Cas lunch lecture will be held on 31 October from 12:30 to 13:30 in lecture hall 1 in the EMC. More information.