In Vivo CRISPR Gene Editing via Lipid Nanoparticle Delivery

Intellia Therapeutics is pioneering in vivo CRISPR gene editing — delivering CRISPR/Cas9 components directly into the body via lipid nanoparticles (LNPs) rather than editing cells outside the body and reinfusing them. Their lead program, nexiguran ziclumeran (nex-z), delivers guide RNA and Cas9 mRNA to liver cells via intravenous LNP infusion, where the CRISPR system disables the TTR gene that causes transthyretin amyloidosis. A second program, lonvoguran ziclumeran (lonvo-z), targets hereditary angioedema and showed positive Phase 1/2 results with potential to become the first one-time treatment for HAE.

In vivo CRISPR via LNP delivery is a fundamentally different paradigm from ex vivo gene therapy (like Casgevy for sickle cell disease, which requires extracting, editing, and reinfusing a patient's stem cells). In vivo delivery turns gene editing into an injection — dramatically simpler, cheaper, and scalable. Intellia also demonstrated that patients can be re-dosed with CRISPR LNPs to achieve additive effects, a first in the field that vastly expands the therapeutic design space.

The platform faces safety challenges — a patient death in the nex-z trial in early 2026 led to a Phase 3 hold, and grade 4 liver enzyme elevations have been observed. But the fundamental proof of concept is established: LNP-delivered CRISPR can edit genes inside a living human body with a single IV infusion. As LNP technology improves to target tissues beyond the liver (lungs, brain, muscle), in vivo CRISPR could become a general platform for treating thousands of genetic diseases with one-time injections rather than lifelong drug regimens.