Biology, Biomedical

Can CRISPR be dangerous in gene therapy?

CRISPR is this new technology, you probably heard about especially if you are a frequently reader here on Qul Mind. It is used to edit DNA segments. This can help us create gene therapies that treat many diseases. Some studies though, show some flaws in this technology.

CRISPR has been used a lot lately in the lab. It is a powerful genetic tool, and although it hasn’t been studied extensively, it has even be used to treat cancer in humans. Compared to previous technologies it has been proven to be very good, especially when working in live animals. If course it still has some drawbacks, and we keep discovering more. Although, even when we discover potential flaws in CRISPR we tend to find ways to work around them. If you want to learn more about gene editing check out our recent article that describes all of them in detail here.

There are many things that can determine the safety of such a technology, when applied to living humans. The delivery method is one of them. Delivering the CRISPR mechanism with viral vectors tends to cause more problems, than using electroporation. On the other hand, electroporation is hard to be used in-vivo. Another aspect of CRISPR that could be improved, is the Cas9 protein itself, the main part of CRISPR. By modifying the structure, some researchers have made it better for certain tasks. Some have even modified it, so that it can edit the methylation status of genes.

The main reason CRISPR has been used so much in research, is it’s precision in editing. It has the ability to cut the DNA in very precise locations and do very precise cuts and modifications. Some studies in the past have shown that in some cases it can cause random mutations. Those mutations tend to be around the target site, and include deletions and insertions of relatively few nucleotides. Those changes occured in a small percentage of cells and eventually researchers found ways to avoid them. Of course some imperfection in a technology like this one is expected. Everything, thus appeared safe and some of the first clinical trials are already planned.

Now, a recent study finds more flaws in CRISPR. What this study reports, is that CRISPR, induces long (many kilobases long) deletions away from the cut site. Other more complex rearrangements were also observed within the genome after CRISPR was used. This can mean that when using CRISPR, especially in cells that can divide, that there can be mutations that lead to cancer. Making CRISPR way riskier to use in clinical trials, given that those mutation occurred in about 19% of the cases. When designing gene therapies, having 20% of the edited cells, have large mutations is very risky and could lead to additional pathologies.

On the other hand, while this research appears to be very good in it’s methodology and have used electroporation to deliver CRISPR into the target cells, they mainly focused on mouse cells. And those did indeed have a mutation rate of 19%, but in the human cell samples, the mutation rate was much more acceptable, around 4-8%. Still, this is a high mutation rate, especially when talking about such huge mutations. But again, this is one study and while good enough on its own, we need to see whether additional studies will agree with such results, if someone will develop a more precise CRISPR version, or if other studies focusing specifically on human cells will report better or worse results.

CRISPR has been a very exciting technology. Not only is it so powerful and easy to use, it is also very cheap compared to alternatives. It has also received a lot of criticism, especially when such studies point at its flaws. I personally would like to see CRISPR and gene therapy succeed, but science is science and facts are facts. If it ends up being unsafe we will have to accept it, and rethink using it for gene therapy, no matter how much this sucks. We will have to see though what the next studies will tell about this.

If you want to find the full article and read it with all the graphs and data as reported by the researchers, there is a link in the sources below. If you like science and technology, make sure to follow Qul Mind on Facebook and Twitter.

Sources: Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements

Image: https://www.flickr.com/photos/nihgov/41124064215

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