Laura Sepp-Laurenzino, PhD
Chief Scientific Officer, Executive Vice President
Intellia Therapeutics
Clinical advances in CRISPR Cas9 Therapeutics: In Vivo and Cell Therapy Applications
At Intellia, we are building a full-spectrum genome editing company. We are deploying the industry’s broadest and deepest toolbox, including novel editing and delivery solutions, to harness the immense power of CRISPR-based technologies for in vivo and ex vivo therapeutic applications, each with the potential to revolutionize the future of medicine. The in vivo programs use our proprietary lipid nanoparticle (LNP) platform to deliver to the liver a two-part genome editing system: a guide RNA specific to the disease-causing gene and messenger RNA that encodes the SpCas9 enzyme, which carries out the precision editing. NTLA-2001 is the first investigational CRISPR therapy to be administered systemically by IV infusion to patients. NTLA-2001 is designed to inactivate the TTR gene in liver cells to prevent the production of misfolded transthyretin (TTR) protein which accumulates in tissues throughout the body and causes the debilitating and often fatal complications of transthyretin (ATTR) amyloidosis. Robust preclinical data, showing deep and long-lasting TTR reduction following in vivo inactivation of the target gene, supports NTLA-2001’s potential as a single-administration therapeutic. Interim Phase 1 clinical data demonstrated that treatment was generally well-tolerated, with mild and transient infusion reactions as the most common adverse event, and delivered rapid, consistent, durable dose-dependent reductions in serum TTR in people with hereditary ATTR amyloidosis with polyneuropathy (n=15). This data provides clinical proof-of-concept for human CRISPR gene editing and substantially de-risks Intellia’s in vivo platform.
