Originally discovered in bacteria, CRISPR quickly became the workhorse gene-editing system underlying the next generation of programmable medicines. Today’s landmark approval by the US Food and Drug Administration of Vertex Pharmaceuticals’ and CRISPR Therapeutics’ Casgevy, the world’s first CRISPR-based treatment, marks a groundbreaking shift in how we tackle intractable diseases.
And it’s a milestone barely a decade in the making: the original publications describing CRISPR’s potential date back to 2012. Since then, CRISPR has transitioned from being a bacterial protein to a gene-editing tool, earned a Nobel Prize, and is now an FDA-approved medicine.
CRISPR uses a protein called Cas9 to cut DNA at precise locations to treat diseases. Casgevy treats sickle cell disease by targeting a specific genetic location that controls the expression of gamma globin, a type of hemoglobin produced by the fetus. By activating the expression of fetal gamma globin in adults, it compensates for the root cause of sickle cell disease. It’s the first potentially curative treatment for the 100,000 Americans, predominantly of African ancestry, and 20 million people around the world that suffer from this painful disease.
Beyond sickle cell, CRISPR represents a shift in how we make medicines: from bespoke discovery to programmable design. If we can make one edit at one location in the genome, it becomes increasingly likely we can make other edits in different locations. Instead of treating symptoms, genetic medicines like CRISPR address the root cause of disease. With more than 7,000 genetic diseases affecting millions, CRISPR offers a tantalizing promise: curative treatments that can be engineered on a grand scale.
This is just the beginning. The genome engineering toolbox is rapidly expanding. CRISPR technology beyond Cas9 is being discovered, evolved, and engineered to create smaller, less immunogenic, and more precise nucleases that expand our capabilities beyond what was previously imaginable. Base and prime editing, along with recent innovations like PASTE programmable gene insertion, are pushing the boundaries, offering more precise and versatile tools for eliminating genetic disorders.
Parallel to these advancements, we are seeing significant progress in the development of new vehicles to deliver genetic cargo. From viruses to lipids, these innovative methods come in all shapes and sizes, enhancing our ability to target previously difficult-to-reach organs, opening new avenues for treating a wide array of diseases that were once considered untouchable.
Although the United States’ first approval of CRISPR came after similar decisions in the UK (and Bahrain!), the FDA is demonstrating an increasing willingness to be flexible and patient-focused, particularly in the context of rare genetic diseases. An adaptive regulatory approach to a modular modality with reusable components has the potential to dramatically speed up the drug development process, paving the way for the next generation of programmable medicines to reach patients who need them most.
The journey of CRISPR from the lab to the clinic is not just a testament to scientific progress, it’s a vivid illustration of how we can learn to adapt and adopt innovations in order to create a future where groundbreaking treatments become commonplace. As we celebrate this remarkable achievement, we must also acknowledge the challenges ahead, particularly in making these therapies accessible and affordable to all who need them, ensuring that this scientific triumph truly benefits everyone.