Almost as soon as researchers began exploring the capabilities of the CRISPR/Cas9 system, they recognized its potential use in targeted gene editing. But the intervening decades have seen slow progress as people worked to determine how to do this in a way that would be safe for use in humans. Decades after the discovery of CRISPR, it was only two years ago that the FDA approved the first CRISPR-based therapy for sickle cell anemia.
Now, following that success, a large Chinese collaboration has described an improved gene editing system that produces more focused changes and fewer mistakes. And they have used it to design a therapy that addresses a disease that is closely related to sickle-cell anemia: β-thalassemia.
Gene editing and its limitations
The CRISPR/Cas-9 system provides bacteria with a form of immunity. It uses specially structured RNA (called guide RNA) that can base-pair with a target sequence. The Cas-9 protein then recognizes this structure and cuts the nearby DNA. This is quite effective when the guide RNA can base-pair with the virus DNA, as the resulting cut will inactivate the virus.
There are a few ways it can be used for DNA editing in organisms like ours. Both of these take advantage of the fact that DNA repair systems in cells often chew up the ends of these cuts before joining them back together. This will often result in small deletions at the site of the cut, which can be used to inactivate the gene. The size of these deletions will vary, so you will have to do some DNA sequencing to find one that inactivates the gene you are interested in, but does not cause any additional damage.
Alternatively, any deleted sequence can sometimes be repaired using a matching sequence, which is usually found on another copy of the same chromosome. If there are lots of copies of the modified sequence with a CRISPR-based cut, it is possible for repair systems to insert the modification into the genome, providing true editing capability. But still, this process is error prone, so people usually need to edit a group of cells and sequence the DNA to make sure the correct changes have been made.
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