Intellia's in-vivo CRISPR bet passes first human test: infused editor cuts disease protein

Intellia Therapeutics is a clinical-stage biotech that sponsors CRISPR-based medicines; the program in this study infuses billions of lipid-nanoparticle carriers into the bloodstream so CRISPR-Cas9 reaches the liver and disables the gene producing the disease protein.

That CRISPR-Cas9 can be infused into the blood and home to an organ, editing disease genes inside the body — unlocking common diseases beyond lab-edited blood cells

CRISPR had already shown it could help patients with blood disorders like sickle cell disease and beta thalassemia, but only by editing cells in the lab or injecting directly into cells needing fixing. Intellia Therapeutics, led by CEO John Leonard, sponsored the first attempt to simply infuse CRISPR-Cas9 into the bloodstream and let it travel to the liver on its own.

The study treated six patients — four in London and two in New Zealand — including Patrick Doherty, a 65-year-old in Ireland with inherited transthyretin amyloidosis, the disease that had killed his father. Within weeks, levels of the destructive protein plummeted, especially in patients who received the higher dose; Doherty said he felt better and could climb stairs again. Researchers reported the results at the Peripheral Nerve Society Annual Meeting and in a paper in The New England Journal of Medicine.

Intellia attacked the hard part — delivery to an organ — instead of stacking another ex-vivo blood-cell edit, so the win generalizes beyond one disease.

The trial results were reported in patients whose disease had killed family members, giving the platform bet a human story that travelled.

The nanoparticles were absorbed by the liver, so the first in-vivo target matched the delivery vehicle's natural behavior.

A negative readout would have capped CRISPR at edited cells; the positive data widened the whole field's addressable diseases.

The winning wedge was delivery, not editing: prove you can reach organs inside the body, and CRISPR stops being a blood-cell treatment and starts being a platform for common diseases

As of June 26, 2021 — the day the data became public — the treatment had no terminal verdict: researchers stressed that patients had to be followed longer and more patients treated to establish safety and how much the approach helps. Intellia framed the readout as a platform milestone for systemic administration, with researchers pointing to non-inherited amyloidosis, heart disease, muscular dystrophy and brain diseases such as Alzheimer's as future targets.