Opinion: The Promise and Challenges of CRISPR-Based Treatments

Gene editing concept_iStock, Andy

Pictured: Gene editing concept/iStock, Andy 

What once was thought of as aspirational is now a reality. In December 2023, history was made when Casgevy became the first-ever gene editing treatment leveraging CRISPR/Cas9 to be approved by the FDA. This Nobel-winning gene editing technology, first reported in 2012, captured hearts and minds over the last decade, with drug developers fervently competing to unlock next-generation treatments (and potential cures) made possible by CRISPR.

Casgevy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, is a one-time gene editing treatment for certain patients with severe sickle cell disease (SCD), a painful, inherited blood disorder that gets its name from the trademark “sickle” shape of a patient’s red blood cells. For treatment with Casgevy, a patient’s blood cells are edited to produce high levels of fetal hemoglobin, which is normally deactivated after birth. This groundbreaking treatment has been shown to eliminate the debilitating pain attacks that are a hallmark of SCD.

In my role as senior director of R&D, cell biology in the biosciences division at Thermo Fisher Scientific, I’ve had the privilege of collaborating with both early- and late-stage companies working to bring CRISPR-based therapies to patients. I can remember the early days of CRISPR, when a small group of researchers were developing various enzymes with the aspiration of someday treating disease. Now, genome editing is here to stay. With so much excitement, let’s reflect on how we got here and map the challenges still ahead.

Key Challenges to CRISPR’s Mainstream Future

While one CRISPR treatment is now approved, we’re still years away from this technology truly becoming mainstream. According to GlobalData, 88% of the CRISPR-based drugs in development are only in the early stages and the next therapy isn’t likely to be launched until late 2025.

In the meantime, the industry can focus on tackling key concerns to improve CRISPR, as well as other gene-editing technologies. Two key safety challenges are the need to reduce off-target effects and to develop highly effective but gentler methods for the delivery of gene editing tools to patient cells.

An even greater hurdle, however, is the lack of widespread access to these groundbreaking treatments. A major contributor to this is cost. In order to treat a wider population of patients, efforts must be made to reduce the costs associated with development and manufacturing. One way to accomplish this is by shifting from an autologous process, where each patient is their own donor, to an allogeneic one, where donor cells are harvested and used to treat multiple patients.

What Does Long-Term Success for CRISPR Look Like?

Although SCD has a relatively large patient population, the approval of Casgevy represents a real turning point for the treatment of rare, inherited diseases. It’s a sign that by enabling and utilizing gene editing technology, we can realistically treat more of these devastating diseases.

Casgevy was just approved in January 2024 for the treatment of beta thalassemia, another inherited blood disorder, and there are many other CRISPR drugs in development, including 24 candidates currently in Phase II. Trials are also underway for drugs that could potentially treat and even cure diseases such as hemophilia, multiple myeloma and type 1 diabetes. And, of course, gene editing isn’t limited to CRISPR; researchers are also exploring other technologies such as TALEN and zinc-finger nucleases across a variety of indications.

Over the next few years, it will be incredibly important to ensure a clear and streamlined regulatory framework. And for ultra-rare diseases with small patient populations, we must find ways to put these therapies efficiently and affordably through clinical trials. Thankfully, public-private partnerships like the PaVe-GT program and the AMP Bespoke Gene Therapy Consortium are bringing industry leaders together to establish a clear framework and simplify front-end workflows for developing gene-editing treatments.

With other technologies in play and many potential cures left to explore, the future of gene editing is bright. Long-term success will come as the industry continues to work together to address challenges, improve access and ensure no inherited diseases are left behind.

Jon ChesnutJon Chesnut is senior director of R&D, cell biology in the biosciences division at Thermo Fisher Scientific. Reach him on LinkedIn.

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