Nick Peel - CRISPR and cancer

Kat - In last month's podcast we took a look at exciting new technology for altering genes, known as CRISPR/Cas9 - or CRISPR for short. In just a couple of years, these tools have revolutionised the world of genetics, raising the possibility of treating illnesses caused by faulty genes, or even genetically engineering designer humans. That's something we'll return to a bit later, but first I wanted to find out more about how laboratory researchers are using CRISPR to delve into the secrets within our genome. To get the low-down I spoke to Nick Peel from Cancer Research UK.

Nick - Scientists have been working with cells that they grow in the lab and they've been tinkering with genes in a bit of a slightly inefficient way and a haphazard way, kind of inserting bits of genetic material into the cells that might target a gene and switch it off. But the efficiency is a bit hit and miss and they're also sometimes not very accurate in the genes that they see cow and kind of untangling the effects of that makes it quite confusing for the scientists and searching for better methods to piece that together is what they've been after.

Kat - These new and more precision techniques, where do they come from and why are they better?

Nick - So kind of a newer invention being using proteins to guide the changes that you might be making to DNA a bit more precisely. So, bringing along with it a certain type of enzyme that's going to cut DNA in a place that you know for sure is where you want that cut to be made or that change to be made. It brings with it greater efficiency and more precision. But the problem that scientists have come across with some of these technologies is they're really expensive and also really time consuming.

Kat - And now, we have CRISPR which, I've heard, best described as sort of a molecular satnav, a very small fragment that guides these molecular scissors to DNA, can cut, can then paste things exactly where you want them with much higher efficiency. How has this changed the game for researchers studying genetics?

Nick - The researchers I have spoken to has basically changed everything for them. It's opening up questions that they never thought were possible before. They're more precise, they're efficient, they cheaper, and an extra thing - they're easier to do. So basically, you can teach anyone how to use CRISPR in a week basically and that's very exciting for researchers.

Kat - How are researchers using these molecular scissors to start unpick what some of these genes do?

Nick - The exciting thing about CRISPR is that you can go as big or as small as you want. So, you can talk of those 3 billion letters and the beauty of the technology is that if you imagine - I've heard it described as imagining the genome like an encyclopaedia - this technology allows you to pick out a volume, open a page, go to a particular page, pick out a word, find a letter in that word, and change the spelling. That sort of precision is just something that researchers have never had access to before and that's why they're so excited about it. And then out of that, you can make those single changes in spelling within DNA and look what that does to cells or whole organisms. But you can either chop out whole genes, rearrange them, tag things onto them so you can see where those cells are, what proteins are doing within cells. It's quite an exciting array of opportunities.

Kat - It is incredible that this really feels like a tool we can use to understand what's all the dark matter of the genome because so little of our genome is the actual genes, the actual things that are the instructions for proteins. All the rest is like... stuff that does something.

Nick - Yeah. The stuff that maybe does something and waving arms around. We need to know what that is and what this technology can do is, as you say, kind of pick into some of those darker regions. You can make these edits to a cell's own DNA. Classically, researchers relying on making a chunk of DNA, sticking into a cell and hoping that the proteins that come out of it that are made of, who knows what amount within the cell, might tell you something. Instead here with CRISPR, you can actually go in and directly change that cell's DNA and look at any bit that you wish and see what happens.

Kat - You work for Cancer Research UK. What are the ways that Cancer Research is using this? Is it going to be a cure for cancer? Can we edit out cancer genes or is it a bit more subtle than that?

Nick - The idea of editing out those kind of faults in DNA that might lead to cancer is an exciting possibility but one that's a lot further away from what the scientists are currently using CRISPR for. What they are doing is taking things like, we know a particular gene fault increases the risk of a certain type of cancer, say. But we don't really know what it's doing, why it might be having that effect. So, what we can do now is start to edit in those precise faults that you do see in people's own genomes, in patient's genomes and really start to see what effect that's having on those cells and build a clearer picture. If that then one day becomes something you can do in people is a much further away discussion.

Kat - I guess it's also very useful for building models of cancer. We've seen in the past few years how we've gone from having cancer cells grown in the lab to bits of tumours transplanted into animals to actually making genetically engineered mice that carry the faults that lead them to develop cancers. I suppose CRISPR is revolutionary here in that you can precision engineer those faults rather than going through the long and tedious process of traditional genetic engineering in mice.

Nick - Absolutely. One of the problems with the older techniques was that scientists were spending years and years, and years, only ever kind of getting to the top level understanding of what one gene might be doing. You can now engineer in multiple different faults in different genes. We know that cancer is a really complicated disease where it's a whole constellation of genetic changes that are going to be behind that disease. You can now start to piece that picture together inside a mouse or a cell or relevant kind of model and get a much better understanding of how the disease works. In terms of kind of working with those models, we know that not only that but being more efficient and more precise in the work that it's doing means that those researchers can work more quickly, more efficiently, and just do a better job all round basically.

Kat - Nick Peel from Cancer Research UK, and I recommend reading the post about CRISPR that he's written for the charity's blog - you can find the link from this podcast's page at nakedscientists.com/genetics
http://scienceblog.cancerresearchuk.org/2016/02/01/crispr-gene-editing-n...