CRISPR 101: A crash course on the gene editing tool that’s changing the world

For something that’s been called “a household name for molecular biologists,” many of you have probably never heard of CRISPR, and don’t know why you should be excited (or, possibly, terrified). It’s all about advanced gene therapy and splicing – and it’s bringing sci-fi ideas straight into reality. Here’s a quick FAQ on the science behind CRISPR and why the world is paying such close attention.

Okay, what is CRISPR and what does it stand for?

CRISPR refers to unusual DNA sequences that help protect organisms by identifying threats – especially viruses – and attacking them. The name stands for Clustered Regularly Interspaced Short Palindromic Repeats. Yes, that sounds a little ridiculous, but it’s actually a very accurate description when looking at the DNA sequences themselves. They are clustered, they are spaced out at clear intervals, and when assigned letter values they do look like short palindromes repeating over and over with slight variations.

CRISPRs were first noticed way back in the 1980s when scientists were studying the genomes of archaea and bacteria. Even in such relatively simple genomes, biologists (notably Francisco Mojica) began to notice these odd sequences that seemed to repeat in a very specific way, with spaces in between. Molecular biologists were sure they had a unique purpose, and the prevailing theory soon became viral defense, which was finally proven in 2007 under the direction of Philippe Horvath. It wasn’t until the early 2010s, however, that researchers began to get especially passionate about the potential behind CRISPR.

So it’s just a DNA strand?

Yes and no. CRISPR has become an enabler of gene splicing, editing, and general experimentation. To understand how, it’s important to first understand the role of CRISPRs in genomes, and how they work to protect organisms (typically, as we mentioned, bacteria). A fair comparison would be telegraphs sending out Morse code. Every sequence is a message about a different attack, and every space is the STOP that ends that message. If metaphors aren’t your thing, Harvard goes into a lot more depth.

When an organism encounters a new and dangerous virus, it doesn’t know how to protect itself or beat back the virus – it has to learn, just as most immune responses do. This can be tricky, because viruses attack DNA directly…but this also makes them vulnerable in certain ways. The CRISPR sequences steal key strands of DNA from the virus and keep them in those little Morse code messages. When a similar virus attacks again, CRISPR responds, “Oh, we recognize this: Here’s how to defeat it!” And it sends the relevant Morse code message on to the battlefield.

Crispr Wikipedia
We told you it was a battlefield. Wikipedia Images

There, little CRISPR soldiers called Cas – enzymes produced specifically for this mission and numbered according to their purpose – bind to viral DNA and slice it at its weak spot, according to the information encoded in the message. This shuts down the virus, and enables the organism to successfully defend itself.

Cas9
A 3D model of the invaluable Cas9 enzyme, and a heartwarming tale for all ugly proteins around the world. NIH Image Gallery | Flickr

…Okay. Why does this matter again?

Because – and it’s hard to understate the importance of this – while CRISPR only uses its telegraph system for defense against viruses, scientists realized that they could use that telegraph to communicate anything. Shut a gene down? Sure (it doesn’t even have to be a viral gene). Turn a gene on? No problem – just telegraph the right instruction over to the enzyme Cas soldiers. CRISPR-Cas9 in particular can become an excellent tool for slicing, recombining, and generally editing DNA, as long as it receives the right messages.

For years, scientists have been working on ways to control Cas9 and, later on, to develop little RNA guides for the Cas9 soldiers and even supplemental soldiers call Cpf1, which are better at infiltration and extraction without risk of mutation. Compared to this, the old, unwieldy tools of gene manipulation looked like caveman clubs next to surgical lasers. It became huge news in the scientific community, and actually started several battles between different groups and researchers about who deserved credit for what.

DNA Wall

So far, so good. But why is this a big deal in the tech world?

Because we are currently at the start of a huge burst of CRISPR experimentation. Our medical devices and scientific knowledge have reached a point where we can put everything we’ve learned from CRISPR into practice and start running swift, effective experiments on gene splicing. For those interested in the cutting edge, Fringe-worthy exploits of science, this is the place to be.

Really? Are you saying that we can edit anyone‘s DNA now?

Good question. We aren’t there yet, but several promising experiments have been conducted. A pair of monkeys was produced with specific gene alterations through targeted mutations using CRISPR techniques. The goal here was to identify genetic problems before birth and disrupt the faulty genes so that they cannot do any damage (it was also a big deal that it worked with monkeys instead of just with mice). Other experiments have shown that the process can also be used to safely alter DNA to resist HIV infection.

However, the most exciting experiment is ongoing in China, where scientists are trying to use CRISPR techniques to remove damaged DNA from the cells of living, adult lung cancer patients. There are a lot of eyes on this project to see how successful it is.

Alright: What does the future of CRISPR look like?

We have a lot of work to do. It’s worth noting that the experiments mentioned above required a long period of expensive research and many, many failed cases before success was reached – and even then, learning how to accurately repeat those experiments is going to take serious labor and investment.

But this is more about refinement than new discoveries: In other words, it’s just a matter of time before we learn to use CRISPR well enough to bring applications into the medical world. When that starts to happen (and it could be only several years away), many of the theoretical questions we have about gene manipulation, designer babies, weaponized organisms, human augmentation, and pay-for-cure systems are going to become a much more than theoretical.

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