Quick Snips: CRISPR

CRISPR is a powerful gene-editing tool that enables targeted therapeutic gene editing, with clinical applications for improving treatment of inherited and/or rare genetic diseases, viral infections, and arresting the progression of cancer. CRISPR gene-editing technology has the potential to revolutionize the treatment of rare genetic disorders, with the first product poised for FDA approval in December 2023.

In early 2023, Vertex and CRISPR Therapeutics submitted the first CRISPR-based therapy in the US, UK, and Europe for the treatment for sickle cell disease (SCD) and beta thalassemia using a CRISPR-based ex vivotherapy called exagamglogene autotemcel (exa-cel). Priority review was granted to the SCD whereas standard review was granted for transfusion-dependent beta thalassemia. If all goes well, this will be a landmark approval, markedly changing the regulatory environment and expanding the possibilities for precision-based medicine.

CRISPR: Revolutionizing Science

Emmanuelle Charpentier and Jennifer A. Doudna discovered the CRISPR method of genome editing, described as “genetic scissors: a tool for rewriting the code of life,” and were awarded the Nobel Prize in Chemistry in 2020. CRISPR has been described as a “revolution in progress” and it has been used in a multitude of basic science and clinical applications, ranging from agricultural (modification of crops) to animal models to therapies for rare diseases. More than 200 people have now been treated with CRISPR-based therapies in clinical trials.

Expanding the Applications of CRISPR

Traditionally, CRISPR had been used to genetically modify cells ex vivo followed by re-infusion of the cells into the patient. Recently, the first in vivo study, which directly edited genes in the body, occurred in 6 patients with transthyretin amyloidosis, was successful, and the company now has clearance to start clinical trials in hereditary angioedema using a new delivery method for in vivo treatment (lipid nanoparticles). Trials have begun in several therapeutic areas such as diabetes, HIV/AIDS, cancer, cardiovascular disorders, and genetic blindness. In the future, CRISPR-based methods may even have the potential to reduce the spread of antimicrobial resistance or to serve as a rapid diagnostic for early diagnosis of COVID-19 or pancreatic cancer. Additional applications include serving as a screening tool for identification of new drug targets and biomarkers with the potential to identify mechanisms of underlying disease.

As CRISPR Technology Continues to Evolve, Concerns Remain

Basic science research is accelerating, and process innovations are making CRISPR-based gene editing more efficient and reducing off-target effects. However, any gene-editing technology has the potential to cause adverse downstream effects, and ethical and safety concerns are still being hotly debated. In the scientific community, that debate centers around treating heritable diseases with gene-editing therapies, especially since the 2018 announcement that He Jiankui had used CRISPR-based technology to create genetically modified embryos. Clinical trials have not been without their stumbling blocks, as evidenced by the October 2022 death of a volunteer who had entered a study for Duchenne muscular dystrophy. Recently, it has been reported that his death was linked to the virus used to deliver the therapy, not CRISPR itself (note: this study has not yet been peer reviewed).

The Bottom Line

CRISPR-based therapies can treat diseases by fixing the root cause: the underlying genetics. This, in addition to their potential as a drug screening tool and use in various diagnostics, has wide (and mostly positive) implications for public health. Stay tuned for updates as we get closer to a potential approval.

Jackie Orabone, PhD, helps clients prepare for FDA Advisory Committee meetings by combining her scientific expertise and research knowledge in immunology with medical communications agency experience. Connect with Jackie on LinkedIn.