CRISPR Gene Editing Therapy Treats Rare Disorder in a Single Dose

CRISPR gene editing DNA

Building on a long history of genetic research and applications, CRISPR gene editing has precipitated a dramatic revolution in clinical medicine and general scientific research. An acronym for “clustered regularly interspaced short palindromic repeats,” this genome editing process has made headlines for its ability to alter DNA in an incredibly precise, rapid, and easy manner.

Now, the Massachusetts-based biotechnology company Intellia Therapeutics is promising to take the science of CRISPR gene editing to a whole new level by developing a “one-and-done” treatment for a rare progressive disorder called transthyretin amyloidosis. In fact, familial transthyretin amyloidosis (FTA), the inherited form of the disorder that Intellia strives to address, affects only roughly 50,000 people around the world.

The roots of FTA lie in a genetic mutation that disorders the shape of the transthyretin protein. Although the disease typically spares its victims from symptoms until adulthood, the misshapen protein slowly begins to accumulate within the body, causing damage everywhere it is found. The circulatory and nervous systems are particularly susceptible to the ravages of FTA.

The Food and Drug Administration has approved multiple FTA treatments that can reduce overall levels of damaging transthyretin protein, but all of these treatments must be undertaken on a regular basis. Intellia hopes that its new CRISPR-driven treatment modality will drop transthyretin levels and keep them there permanently after just one dose.

Most comparable CRISPR gene editing disease treatments on the market today involve multiple doses and/or multiple steps. For example, Vertex Pharmaceuticals and CRISPR Therapeutics have successfully employed CRISPR gene editing to treat sickle cell disease, but their approach requires removing blood cells from a patient, genetically editing those cells in a lab, and finally reinfusing the edited cells into the patient’s bloodstream.

By contrast, Intellia’s new transthyretin amyloidosis treatment only requires a single step. In fact, Intellia became the first biotechnology company to infuse a CRISPR gene editing therapy directly into a patient’s body during its FTA clinical trial in November of 2020.

Injected into the patient’s bloodstream, the Intellia treatment travels to liver, where the toxic protein that causes the symptoms of FTA is produced. At this site, it halts the creation of malformed transthyretin by deactivating a specific gene.

Specifically, the Intellia treatment deploys a CRISPR enzyme called Cas9, which scientists describe as a pair of molecular scissors. By cutting out the gene that transcribes the production of the toxic transthyretin, it can stop its production and eliminate its buildup.

As reported in the February 28, 2022 edition of the Boston Globe, Intellia’s first small CRISPR gene editing therapy study shows tremendous promise. Globe staff writer Ryan Cross reports that a single infusion of the Intellia treatment resulted in extremely low levels of toxic transthyretin protein for a full a year.

Comprised of six people with FTA, the Intellia study was conducted in partnership with Regeneron Pharmaceuticals. After tracking their subjects for a year, researchers determined that even low doses of the one-time CRISPR-Cas9 treatment dramatically decreased levels of the toxic transthyretin protein and kept them low for the duration of the study.

Since publishing their landmark study, Intellia and Regeneron have expanded their clinical trials to include 15 people and test a regimen of four treatment doses. The latest data released by Intellia suggests that higher doses of the treatment will yield even better results than those of the initial study from last year.

When asked to comment on Intellia’s accomplishments, Dr. Vaishali Sanchorawala, director at both the Boston Medical Center and Boston University School of Medicine’s Amyloidosis Center, expressed a wealth of cautious optimism. Although she warns that longer-term studies are needed to determine the full potential of the Intellia therapy, Dr. Sanchorawala predicts that CRISPR gene editing will become a game-changing treatment for the rare disease in the near future.