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CRISPR: Dissecting Human DNA


CRISPR is a site-specific gene editing tool. Image Courtesy of the Broad Institute. Scissors [Composite © iStockphoto.com. Double helix © Can Stock Photo Inc.]

The cut and paste keyboard commands (Ctrl/⌘ X and Ctrl/⌘ V) may seem like commonplace instructions to most computer users, and for good reason. The ability to cut a piece of text and paste it into a new section of a document is an incredibly useful function. Imagine being able to do the same thing, but in the DNA of a living person. This cutting and pasting of DNA, otherwise known as genome editing, was barely conceivable a few decades ago, but is a very real tool in today’s world.

One of the most popular methods of genome editing is a technique called CRISPR. To understand what CRISPR is and how it works, it is useful to consider how it was first discovered. CRISPR was first observed as a natural mechanism. Bacterial cells use CRISPR to protect themselves against viral infections. When a virus infects a bacterium, the virus inserts its own DNA into the bacterium. This is detrimental to the bacterium and can cause it to die. However, the bacterium can defend itself by using what are essentially molecular scissors: a way to cut up the viral DNA and stop the infection.

One of the most incredible parts of this phenomenon is that once the bacterium has successfully cut up the viral DNA, it can take a strand of that chopped-up DNA and insert it into its own bacterial genome. This serves as a molecular record of the infection. If the same strain of virus infects this bacterium again, then the bacterium is much better prepared to recognize it and defend itself.

Recently, scientists realized that this scissor-like bacterial mechanism can be adapted for use in both the laboratory and the clinic. This process can aid in one of the most important aspects of molecular biology: understanding the function of various genes.

For instance, assume that a researcher hypothesizes that Gene X causes brain cancer. The researcher may use cells derived from a brain cancer patient and subsequently grown in a culture dish in the lab to test her hypothesis. Our researcher can use a tool like CRISPR to knock out (i.e. remove) Gene X and see what happens as the cells propagate. If the modified cells grow much more slowly than normal, then the deleted Gene X is likely related to cell growth.

Having the ability to pinpoint a specific sequence of our DNA and delete it in a lab setting is immeasurably powerful. In addition, scientists can swap in new sections of DNA or, in lab-speak, knock-in. This is when one DNA sequence is switched for another. For instance, let’s now assume that our researcher believes the reason Gene X causes brain cancer is a mutation in Gene X. After more research, she finds out that there are two variants of Gene X. The normal (or wild-type) form is present in people without brain cancer. However, the other variation of Gene X includes a mutation.

This mutation leads to an abnormal form of the specific protein associated with this gene, which may be what leads to brain cancer. (Aberrant changes at the protein level are often the reason why gene mutations cause disease.) The researcher can now use CRISPR to switch out the mutated form of Gene X that may cause cancer with the wild-type form of Gene X, and see if this decreases cancer growth. With the advent of CRISPR, such knock-in and knock-out experiments can be accomplished very efficiently in the lab, making CRISPR one of the most popular techniques in biomedical research today. Down the line, this technique can potentially translate from the laboratory to the clinic as well.

For instance, if a patient has a disease caused by a genetic mutation, doctors could use CRISPR to cut out or inactivate the problematic gene, or replace it with a corrected form. This would make it an incredible therapeutic tool. However, this is not a technique available to clinicians today.  Before it is accepted as a clinical tool, much research on the safety of using CRISPR in humans is still required. However, the practice is slowly making its way to clinical trials. In a few short years, research may evolve to a point where genome editing for curing diseases is as prevalent as cutting and pasting on a computer keyboard.



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