Using CRISPR to treat genetic diseases
Since its initial development, CRISPR has always carried a bold ambition: to treat humans.
In the medical world, some of the most urgent and daunting challenges are diseases and conditions that have long resisted any reliable cure — cancer, Alzheimer’s disease, Parkinson’s disease, and diabetes are just a few. Now, human gene editing is giving scientists a new path forward. With the ability to edit DNA finally a reality, many are beginning to wonder if these diseases could be eliminated at the source, preventing any pain or treatments altogether.
One such case is sickle cell disease, which has become a major focus in the push to make CRISPR a practical medical tool.
Sickle cell disease is an inherited disorder affecting hemoglobin, the protein in red blood cells responsible for transporting oxygen throughout the body. Normally, these red blood cells are flexible discs that can easily move through blood vessels. However, the sickle cell mutation produces abnormal hemoglobin, which causes these cells to become stiff and curved, taking on the characteristic “sickle” shape. These misshapen cells struggle to move through the bloodstream and can clump together, blocking blood flow entirely and leading to severe complications.
Before CRISPR, the only available treatments for this disorder were bone marrow transplants and blood transfusions, both dependent on finding a matching donor, which can be difficult. Not only that, but donor treatments also carry the risk of graft-versus-host disease, which is when the received cells see the recipient as foreign and attack them, an often fatal internal battle.
“Especially with sickle cell disease and other diseases, where blood transfusions are a really popular treatment but are really hard to obtain because you need donors with matching tissue and blood types, CRISPR would be a great tool to use and edit those genes instead, because you don't need donors,” said junior Arina Bolsakova, a Carlmont BTI student currently researching how sickle cell disease can be cured with CRISPR.
While CRISPR offers immense promise, it also brings many concerns, the most commonly cited being off-target effects, where gene editing unintentionally alters parts of the genome beyond the intended target.
Still, Hall says these risks can be almost fully mitigated with the introduction of better tools and careful design.
“When you're doing a CRISPR experiment from start to finish, you design your guide RNA, and there are online tools that help you find out if the sequence that you're trying to use is going to potentially be a match with anywhere else in the genome,” Hall said. “So, if you do a bad job designing your guide sequence, or if you don't double and triple-check it against the genome and against these various guide RNA design tools, then off-target effects are a lot more likely. But if you design your guide RNA very specifically, then there should only be one place in the genome that matches. So, I think that off-target effects are becoming less of a concern.”
Hall also notes that much of the current disease treatment work is well-suited to reduce these risks because of how targeted the process is, often occurring outside of the body.
“With sickle cell disease, they take out bone marrow cells that are responsible for making red blood cells, edit those, and then put them back in the person's body. So, the effects should be localized to only the bone marrow cells,” Hall said. “A lot of the CRISPR therapies that we're thinking about right now are not editing every cell in a person's body, but just editing cells that are relevant to the disease or the problem that we're trying to combat.”
