The Promise of CRISPR-Cas

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Our bodies are made up of various cell groups that can do different things depending on the combinations of proteins they contain. Proteins can do wonderfully complex things, from acting as oxygen sensors to molecular motors. All of the information for making these proteins is stored in our DNA. The DNA consists of four molecules (commonly called by the letters A,T,G,C) put together in long strings of specific sequences. Each part of our DNA containing the information for creating a single protein is called a gene, thus our DNA holds the “genetic code” for all the proteins our body can make. The “letters” in our genes are converted to another type of molecular-letter-string called mRNA, which is then converted into protein.

Courtesy of Genetic Alliance UK

We get our DNA from our parents, and have a separate paternal and maternal copy of the entire human genetic code. However, sometimes you can inherit a gene that leads to disease — your DNA creates a slightly altered or dysfunctional protein that can affect certain processes going on in your body. For example, people with sickle cell disease have a gene for hemoglobin that is one “letter” different from the “normal” code. Hemoglobin is the protein inside your red blood cells that lets your body transport oxygen. When the code has been mutated through this one-letter change, it gives your red blood cells a sickle-like shape that can lead to many harmful effects.

Fixing a single base-pair mutation in our DNA could drastically change the shape of our blood cells, preventing sickle cell disease. Courtesy of Megan Hoban, UCLA.

Since many diseases are caused by very small alterations of our genetic code, it would be great if there was a way to change those codes carefully and correctly. While many methods have been designed to change the sequence of DNA, none of them are as easy to apply or as broadly effective as CRISPR-Cas, or simply CRISPR systems. CRISPR systems are groups of  proteins that are able to cut nucleic acids, like DNA, at specific points, when they have “guide RNAs” attached to them. To guide a CRISPR system to a pre-determined point in our DNA, we take advantage of the base pairing code. DNA is double stranded, and the letters A and G interact with the letters T and C on the other strand, respectively. Let’s say our target gene has an A at a specific position. Based on this complementary matching of letters, if we make our guide RNA have a T at the equivalent spot, it can interact with that A, too. Now if all the letters in our guide RNA are complementary to a certain gene sequence, the Cas protein will be chemically attracted toward that spot in your DNA. When it gets there, it will bind to the DNA, similarly to a Velcro strap, and make a precise cut. This way, we can make targeted small changes to specific genes causing known diseases, without causing any wide effects to the rest of the genetic code.

CRISPR interacting with DNA. Courtesy of Mirus Bio.

The ability to make site-specific cuts is an incredibly powerful tool in genetic engineering. Is there a protein you don’t want a cell to make? If you know the sequence of that protein, and therefore the sequence of its gene, you can cut it out. You can even add new genes by making a cut and putting something new in the middle — similar to ripping a piece of cloth apart and stitching a new fabric in the middle. With tools for genetic editing getting better every day, this is going to be a reality soon.

Even though CRISPR is a very powerful tool, there is plenty of debate in the scientific community about the rules that should govern its use in medicine. Since this method can be used to potentially eliminate diseases but also add features to organisms, important ethical issues have come up regarding use in animals and humans. The topic reached the news worldwide when a Chinese scientist, He Jiankui, announced that he used CRISPR to genetically modify two babies that were born through in vitro fertilization. The researcher had not received any official approval for these experiments and he was eventually fired from his position and is now facing prison time.

CRISPR ethics is still a fairly new field, but many government agencies like the National Institutes of Health have started working with bioethicists to study the best approach for regulating genetic editing. Since CRISPR is already widely used in research and even human clinical trials, scientists should always work in coordination with funding and governing agencies to continue exploring its benefits in an ethical and safe manner.  

— Devin Bog & Vicky Kanta