CRISPR/Cas9: A Giant Leap in Gene Editing

DNA Molecule
Image: Google Images

Gene editing. It seems like a pretty dense topic, right? Well, that’s because it is. Just because it is dense though, doesn’t mean that we shouldn’t be talking about it. In fact, the potential ramifications of gene editing mean we most definitely should be talking about. Right now the big news on the gene-editing front is the CRISPR/Cas9 mechanism, and Science on the Rocks is here to tell you about it and more importantly…why do we care?

The Background:

There is A LOT of background information for understanding in great detail gene editing and the CRISPR/Cas9 mechanism. So much so in fact that there are hundreds of books and papers published on the subject. Luckily, in order to appreciate the brilliance of the science and the gravity of its application you really don’t need to know much of it. Here are some of the things, however, that you should know.

CRISPR stands for clustered regularly interspaced short palindromic repeats. Knowing what it stands for is not nearly as useful (or interesting) as what its actual function is. CRISPR is like an ancient immune system for bacteria. Immune systems (that thing you drink those vitamin-C powders for) are what fight off viruses and make sure that an organism stays healthy. Unlike you, me, and pretty much every other animal, bacteria do not have an immune system that actively fends off viruses. While we have antibodies and other kick-ass weapons to beat things such as the common cold or strep throat, bacteria protect themselves more passively with CRISPR. When a virus infects a bacterium (no need to search the web, this is just the singular form of bacteria), the bacterium “steals” bits of the virus’s DNA. These bits of DNA are inserted very precisely into the DNA of the bacterium.

You are probably thinking why would anything, unicellular bacterium or otherwise, purposefully insert part of a virus’ DNA into their DNA? The answer is really quite simple. The bits of viral DNA taken by the bacterium allow the bacterium to recognize the virus. Once the bacterium knows what to look for, the next time that mean old virus comes around looking for trouble, the bacterium will be ready to fend it off more quickly and efficiently. Pretty cool huh? Bacteria are using viruses’ own DNA against them to better fight off infection. Makes taking an orange, fizzy drink that tastes like the world’s worst mimosa seem pretty lame by comparison.

Now you have at least an idea of what CRISPR is, so what next? Here is a hint: CRISPR/Cas9. The Cas9 part of the mechanism is pretty straightforward compared to the CRISPR portion. Cas9 is essentially a protein, or a machine if you will, that can cut both strands of DNA ­— if you didn’t do so well in high school biology then news flash! DNA is double-stranded. Furthermore, it can cut DNA incredibly precisely based on a guide RNA — a small piece of genetic material that matches a sequence of the target DNA.

The Mechanism:

So, we have CRISPR, a system which can very precisely identify DNA and interact with it. We also have Cas9, which can very precisely cut both strands of DNA. Do you see where we are going with this? It’s OK if you don’t because many scientists didn’t for many years. That is until the brilliant molecular biologists Jennifer Doudna and Emmanuelle Charpentier came along to connect the dots (and the DNA).

In a 2012 paper, these two groundbreaking scientists first brought up the notion that the CRISPR/Cas9 system could be used to edit genes in cells, including human cells. It not only earned them an incredible amount of well-deserved notoriety in the scientific community, but also a plethora of awards.

While the entire proposed mechanism for CRISPR/Cas9 gene editing is fairly dense, the basic idea is quite, well, basic. The guide RNA (last sentence of the background section) of Cas9 is programmable. What that means is that scientists are able to program any sequence they want for the guide RNA in order to find a specific, matching sequence of DNA. Once the guide RNA is programmed, the Cas9 protein will cut the DNA of a cell in the exact location that it was programmed to. Once cut, the DNA strand will either try to repair itself naturally or a small DNA strand that fits in between the cut ends can be inserted. So scientists are able to cut a specific sequence of DNA and then add in whatever sequence they so choose.

For a great animation explaining this mechanism by the geniuses at MIT click here.

Why You Should Care:

If you feel like this is a lot of science mumbo-jumbo, and aren’t jazzed about the CRISPR/Cas9 gene editing mechanism, stay with me because you are about to be jazzed. This fairly new scientific discovery could change EVERYTHING about how we handle disease. Our DNA codes for everything about us, including any genetic diseases or even how susceptible we are to things like diabetes, heart disease, or obesity. As we learn more and more about the actual sequence of the human genome (the order of the A, C, T, and G’s that make up our DNA) we start to determine what sequences lead to these diseases or a susceptibility to them. These sequences that code for a certain outcome are called genes. But so what? We know a certain gene might code for a horrible disease, but what does it matter? That person still has the disease right? If only there was a mechanism by which we could find that gene, disrupt it (say with a cut or something), and replace it with a healthy version of the gene. Oh, what was that? CRISPR/Cas9 gene editing can do that you say? Yes! It can do that. This cheap and quick method of gene editing could not just treat or cure a genetic disease, but genetically dismember it entirely (I know, kind of gruesome but you get the point).

The jazziness doesn’t stop there though. As I mentioned earlier, our genetic code determines everything about us. That includes your eye color, skin tone, height, you name it, and genes code it. While CRISPR/Cas9 could eradicate a genetic disease, it could also lead to “designer babies”, the term affectionately given to children who have an altered genetic code to result in specific characteristics. Imagine a future where choosing the features of your child was like picking the toppings on a burger; “I’ll have a 6’3”, athletic, blue-eyed boy, hold the male pattern baldness”. Even further, imagine this technology being weaponized to genetically engineer the perfect soldiers; all of the brawn, agility, and loyalty, but none of the empathy or self-expression. It seems like science fiction right? But with CRISPR/Cas9 gene editing, the “designer baby” reality is right around the corner (which for science means only a few decades or so away). In fact, the possibility is so close to reality that Jennifer Doudna — the genius behind the CRISPR/Cas9 gene editing application — has a TED talk dedicated to discussing the bioethics of the discovery.

Conclusion:

Of all the currently emerging scientific technologies, this is one of the most difficult to talk about. The science is fairly complex, the research is relatively new, and the possibilities that it presents are ever expanding. Even though it is one of the more difficult ones to understand, it is one of the most important for us, as the general public, to talk about. The implications are unparalleled. There is no scientific technology that comes to mind that has so much potential for good and for bad. The time to talk about what if we could eradicate a genetic disease or “design” our children how we want is rapidly coming to an end. Now, it is the time for all of us, not just scientists, to discuss how we should use this technology. Policies will have to be made, ethical applications discussed, and philosophical questions asked, to make sure CRISPR/Cas9 gene editing is used properly. So should we care about this technology? I have a better question. Can we afford not to?