CRISPR‑Cas9, a gene-editing tool originally part of bacterial immune defense, has been used for everything from a “de-extinction” of dire wolves to the creation of human-compatible pig organs to the controversial—and illegal—birth of gene-edited babies.
In 2023, the FDA approved the first-ever CRISPR-based medicine, exagamglogene autotemcel (brand name Casgevy), to treat sickle cell anemia. Beyond that, there are dozens of gene-editing trials that use CRISPR in treatments for other conditions like chronic Hepatitis B, lymphoma, and urinary tract infections.
All this happened relatively quickly after researchers Jennifer Doudna and Emmanuelle Charpentier, who submitted the first CRISPR patent in 2012, published a landmark paper that same year describing how clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated Protein 9 could be repurposed as “programmable DNA scissors,” kickstarting a genetic revolution.
“It’s really a ‘before and after’ in the history of humankind,” Isabel Esain Garcia, a postdoctoral researcher in Doudna’s lab at the University of California, Berkeley, told Healthcare Brew. “I definitely think that the future is going to be CRISPR-based clinical [applications].”
But while this technology has catapulted medicine and research forward, the rollout of CRISPR-based therapies—the technique’s most high-stakes application—remains complex. The next frontier is not just what CRISPR can do, but how to get it efficiently and equitably to patients.
Medical advances, questions
About a year ago, the sickle cell community was “buzzing,” Crawford Strunk, a pediatric hematologist-oncologist and vice chief medical officer of the Sickle Cell Disease Association of America, told Healthcare Brew. “We had [Casgevy] approved. It was great.”
But rollout has been slow, in part because companies that perform the therapy are still ramping up capacity.
The process is also very involved and time-consuming for patients. They must stop their medications and undergo preparatory therapies for at least three months before their stem cells can be extracted. The stem cells are then sent off to the lab, where technicians use CRISPR to make a customized gene edit that can stop cells from sickling and test whether the edit worked—a process that can take up to six months, according to Casgevy’s official website.
Patients subsequently undergo chemotherapy and then, finally, their modified cells can be transplanted back into their bodies. The full process can take up to a year for patients, Strunk said.
The treatment also doesn’t work for everyone. For instance, a patient’s marrow can sometimes be so unhealthy that CRISPR can’t sufficiently fix it, Strunk said. Casgevy-treated stem cells have to be at a “certain level of transformed” for the FDA to allow them to be put back into a patient. Some patients find out only after undergoing months of prep and collection that they don’t meet the cut, he said.
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“There’s access issues in terms of who the right patients are. There’s access issues to the available centers…Can you afford to do [the preparation] for a year before you get gene therapy?” he said.
There’s also the cost: $2.2 million per patient for the one-time infusion therapy. This poses a “major ethical issue in terms of equitable access and global health,” researchers argued in an October 2024 paper in the CRISPR Journal.
Vertex Pharmaceuticals, the biotech company that makes Casgevy, has estimated about 16,000 patients ages 12 and older are eligible for its therapy. But by December 2024, one year after its approval, a little more than 40 patients worldwide had begun having their stem cells collected for the treatment.
CRISPR in research
CRISPR’s utility goes far beyond human genome manipulation. Its ability to control gene expression has been crucial in research labs.
Huirong Xie, a research specialist and codirector of Michigan State University’s Transgenic and Genome Editing Facility, told Healthcare Brew her team uses CRISPR to create animal and cell models for scientists to study diseases and test out potential cures.
This manipulation can be done with other gene-editing techniques, but CRISPR is a cheaper and quicker gene-editing tool than those that came before it, Xie added.
Hana Totary-Jain, associate professor at University of South Florida Morsani College of Medicine, told us she worked on research that used CRISPR to turn on a large gene in order to understand what it does. That research revealed more about that gene’s role in protecting the placenta from viral infections.
“It’s a very fundamental tool for scientists to use to answer many questions,” Totary-Jain said.
The future
Strunk believes the future is in vivo gene therapy, which would use CRISPR to make changes to a patient’s DNA while it’s inside their body rather than removing and modifying cells outside it. He thinks this could be more accessible and potentially cheaper than current ex vivo gene therapies like Casgevy, and could eliminate the need for chemotherapy.
But in vivo editing brings new concerns about accidentally affecting other parts of the genome and body.
“Off-target effects can elicit deleterious changes to the genome, which could result in new pathologies,” Catherine Kendig, associate professor of philosophy at Michigan State University, told us via email.
Esain Garcia said the Doudna Lab is one of many working to find the best and safest method to deliver CRISPR treatments alongside discovering and developing novel gene and epigenome editors.
“Definitely one of the biggest challenges is to make sure that you can develop a technology that is going to be very precise and on target,” Esain Garcia said.
