What is CRISPR, exactly?

So this post is going to be a bit different but I’m so excited about CRISPR that I couldn’t resist writing about it!  I hope you find it interesting  🙂

CRISPR (clustered regularly interspaced short palindromic repeats – I know, let’s just stick to CRISPR!)  are parts of DNA where the same code is repeated over and over again. Between these repeats are unique messages. To simplify things a lot you could think that the DNA is arranged like this: …AAAA TGACA AAAA GTAAC AAAA CCCGT AAAA…  Much to the surprise of scientists, CRISPR turned out to be a vital part of the immune system of bacteria. Even more surprisingly, it turns out that the same system could revolutionize the way in which humans manipulate DNA.

If you’re a bacterium, viruses make your life a living hell. It has been estimated that viruses kill 40% of all the bacteria in the ocean every single day. Viruses are essentially protein shells containing genetic information. They reproduce by invading a cell, releasing their genetic material inside it, and forcing the cell to ignore it’s own needs and produce new viruses instead. Eventually new viruses burst out to infect new cells and the original cell dies. It’s not pretty.

Bacteria have, however, been around for a long time and they have come up with ways to protect themselves. It turns out that the unique messages between the DNA repeats are actually parts of the DNA of viruses that have tried and failed to invade the bacterium. When the bacterium has managed to destroy a virus it has cut the viral DNA into pieces, spared a piece, and inserted it into its own DNA.

Here things get interesting. The bacterium uses the inserted piece to generate more copies of the viral DNA. These are then attached to proteins called Cas9. Now, you might think of the Cas9 proteins as highly specific scissors. They go around and compare every DNA that comes their way to the piece of DNA they carry. Nothing probably happens for a long time. But then… The same virus invades the bacterium. The Cas9 protein bumps into it. It compares the viral DNA to the DNA it carries, they match, and the Cas9 protein shreds the viral DNA into pieces before it gets the opportunity to do any damage. Problem solved.

What makes the CRISPR/Cas9 system so interesting to people like biomedical scientists is that it’s almost ridiculous how easy it is to edit the DNA of organisms like humans with it. You can give the Cas9 protein whichever piece of DNA you want, and if you then let it loose in a cell, it goes to the nucleus, finds the corresponding sequence of DNA and chops it off. Lots of mutations happen in cells every day and it’s not uncommon to have the whole DNA chain ripped in two pieces. Our cells are prepared for this – they know how to put the loose ends back together. They aren’t very smart though. If they notice anything in the vicinity that even faintly resembles the lost part, they’ll put that back in. This means that we can knock out genes easier and with more specificity than we’ve ever been able to before, and that we can also put new genes to where we want them to go much more efficiently than before.

This has huge potential in the treatment of genetic diseases. There are lots of terrible diseases such as cystic fibrosis that we could cure if we only had a way of slightly tweaking the DNA. CRISPR might be that way. In fact, researches have already been able to restore sight to blind rats that have suffered from a genetic disease. Diseases that affect millions of people like cancer, Alzheimer’s disease and Parkinson’s disease could be a thing in the past 100 years from now. We might even be able to manipulate the genes that affect aging (ie. genes involved in DNA repair after mutations) and increase our  lifespan.

Even though CRISPR has huge advantages compared to the gene editing techniques we’ve been using before, there are still big problems to it. It’s still far from working in 100%, or even in 50%, of cases. It’s easy to use it in dividing cells in a petri dish on the lab table, but things get far trickier if you try to use it in the cells of an adult animal. We also need to remember that if we used CRISPR in humans we would be letting a thing whose primary function is to destroy DNA run free inside our cells. The DNA sequences are 20 bases long, and the Cas9 protein can tolerate a difference of as many as 5 bases. That would mean that it would cut any 20-base sequence of DNA that had a minimum of 15 bases in common with the DNA it carries. In bacteria this is not much of a problem since they don’t have lots of DNA anyway, but humans have over 3 billion base pairs in their genome. That’s 3 000 000 000. That’s a really big number, and you could expect that just by chance there would be a few places where this 15-bases-out-of-20-criterion would be fulfilled. That’s a problem, because we don’t to cause changes that would interfere with some vital functions or even activate some cancer-causing gene.

There are also lots of ethical problems surrounding the use of CRISPR. Is it even right to interfere with something as fundamental to life as DNA? Where would we draw the lines – if a mother wanted to remove the gene that would give her infant cystic fibrosis I’m sure that no one would disagree. What if she was abnormally short and she didn’t want her child to go through the same experience so she wanted to make him taller? What if she wanted the child to have clear blue eyes instead of the ugly muddy color that everyone in her family had? With the advancement of CRISPR we could have the power to make irreversible changes to the qualities of people who haven’t been born yet and so haven’t had the chance to consent. In what circumstances would that be justified?

CRISPR is coming, whether we want it or not. There are problems but I am sure they are nothing we can’t overcome. Science is moving fast and I think it’s enormously important that we acknowledge the things that probably lie ahead and begin to formulate our thoughts about them. We will need to make decisions about genetic engineering, about the lines we should or shouldn’t cross, and when it comes to that, we should have opinions that are well-informed and well-articulated.

 

 

 

 

Sources: I’m such a nerd that I remembered all this and I don’t have the energy to search up every website I might have read about CRISPR on. I recommend the Radiolab podcast on the topic though (all their content is brilliant) and the articles on http://www.sciencemag.com.