CRISPR Human Trial Shows Genetic Diseases May Be Treated

Intellia Therapeutics and Regeneron Pharmaceuticals, two biotech companies, have announced clinical data supporting the safety and efficacy of in vivo CRISPR genome editing in humans.

“These are the first ever clinical data suggesting that we can precisely edit target cells within the body to treat genetic disease with a single intravenous infusion of CRISPR,'' says Intellia President and Chief Executive Officer John Leonard in a press release issued by the two companies. “With these data, we believe we are truly opening a new era of medicine.”

Preliminary data from an ongoing Phase 1 clinical study of NTLA-2001 have been presented at the 2021 Peripheral Nerve Society Annual Meeting. NTLA-2001 is a genome editing candidate that is being developed as a single-dose treatment for transthyretin (ATTR) amyloidosis. The patients who participate in the trial receive a single dose of NTLA-2001 via intravenous administration.

ATTR amyloidosis is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tissues, predominantly the nerves and heart. ATTR amyloidosis is a progressive and fatal disease that usually requires chronic, lifelong treatment. But now we can hope that a single injection of a CRISPR drug could treat this and other genetic diseases.

A study is published in The New England Journal of Medicine. It reports that, in a small group of patients who participated in the trial, administration of NTLA-2001 had only mild adverse effects and led to decreases in the concentration of the TTR protein. A single 0.3 mg/kg dose of NTLA-2001 led to 87% mean reduction of TTR.

A commentary is published in Science. It notes that, so far, CRISPR treatments required removing cells from a patient, modifying them with CRISPR in the lab, and then putting them back into the body. But in this case, a medical first, a non-personalized CRISPR drug injected in the blood has “nearly shut off production of toxic protein by their livers.”

Another commentary is published in Nature News. It notes that the preliminary results of “this landmark clinical trial suggest that CRISPR–Cas9 gene editing can be deployed directly into the body to treat disease.” The ability “to edit genes directly in the body would open the door to treating a wider range of diseases.”

“Thanks to large-scale human genetics research, there have been many new genetic targets identified and confirmed to have an impact on human health,” says George D. Yancopoulos, President and Chief Scientific Officer of Regeneron. “Combining this knowledge with the precision and enhanced convenience of a single CRISPR infusion unlocks new possibilities in treating - and potentially even curing - life-threatening and historically difficult-to-address diseases.”

CRISPR pioneers Emmanuelle Charpentier and Jennifer Doudna have been awarded the 2020 Nobel Prize in Chemistry for discovering “one of gene technology’s sharpest tools.” These new results suggest that we ain’t seen nothing yet. CRISPR is sharper than some may have thought, and could have a really world-changing impact.