Intellia Therapeutics Presents Preclinical Proof of Concept for CRISPR-based In Vivo Editing of Bone Marrow at Keystone eSymposium

CAMBRIDGE, Mass. – Intellia Therapeutics, Inc. (NASDAQ:NTLA), today announced the presentation of preclinical data establishing proof-of-concept for non-viral genome editing of bone marrow and hematopoietic stem cells (HSCs) in mice. This represents the company’s first demonstration of systemic in vivo genome editing in tissue outside the liver using its proprietary non-viral delivery platform. Gene editing of HSCs in vivo via a non-viral delivery system offers the potential to transform the treatment of sickle cell disease (SCD) and other inherited blood disorders by overcoming the complexity and safety risks of ex vivo approaches. The company is presenting these data today at the Keystone eSymposium: Precision Engineering of the Genome, Epigenome and Transcriptome, being held virtually March 8-10, 2021.

“This new data supports the possibility of delivering a safer solution to treat blood disorders, including sickle cell disease, by avoiding the need for bone marrow transplantation,” said President and Chief Executive Officer, John Leonard, M.D. “We’ve demonstrated we can expand our in vivo capabilities originally designed for liver applications to other tissues and achieve therapeutically meaningful levels of gene editing, reinforcing the promise of Intellia’s modular platform to transform the lives of people living with genetic diseases.”

Presentation Details

Title: “In Vivo Genome Editing of Hematopoietic Stem and Progenitor Cells”
Session: Delivery
Date and Time: March 10, 2021, 11:50 a.m. – 12:05 p.m. ET
Presenting Author: Sean Burns M.D., senior director of Intellia’s Disease Biology and Pharmacology group

The presentation can be found here, on the Scientific Publications & Presentations page of Intellia’s website.

CRISPR/Cas9-based genome editing is well suited to the treatment of hereditary blood disorders, such as SCD. However, the current requirement for ex vivo manipulation of HSCs and toxic myeloablative transplantation regimens are significant barriers to widespread adoption of this approach. An in vivo gene editing strategy, in which CRISPR/Cas9 is delivered systemically as a treatment into patients, could greatly reduce the risk, cost and barriers to treatment associated with ex vivo genomic modification of HSCs. Such an approach could provide a one-time, curative treatment option for patients worldwide who are suffering from SCD.

About the Study

Intellia’s non-viral delivery platform enables systemic administration of CRISPR/Cas9 to disease-relevant tissues. The findings being presented today demonstrate the applicability of this platform for editing cells within the bone marrow. In this proof of concept study:

  • Lipid nanoparticles (LNPs) enabled transient and well-tolerated delivery of CRISPR/Cas9 to murine and human hematopoietic stem and progenitor cells (HSPCs) in mice
  • Dose-dependent editing was seen in whole bone marrow as well as HSPCs, with editing levels in hematopoietic stem cells found to be durable for over one year after a single LNP administration
  • Editing increased upon repeat LNP administration, potentially enabling a “treat-to-target” approach
  • Transplantation studies showed that in vivo edited HSPCs retained their capacity to provide long term, multilineage reconstitution of bone marrow
  • In vivo editing in a humanized mouse model demonstrated relevance of the approach to human HSPCs

Intellia is currently building upon this preclinical work, towards a potential cure for SCD, with a grant from the Bill & Melinda Gates Foundation.

About Sickle Cell Disease

Sickle cell disease (SCD) affects >100,000 people in the U.S.and millions of people worldwide, with highest prevalence in sub-Saharan Africa and India. SCD is caused by a mutation in the beta globin gene that leads to sickling of red blood cells (RBCs) and clotting in small arteries. The disease is characterized by severe pain and multi-organ injury, including in the brain, heart, lungs, kidneys and joints, with greatly reduced life expectancy and quality of life. Standard of care therapies include hydroxyurea and frequent RBC transfusions from healthy donors. Allogenic hematopoietic stem cell transplantation is reserved as a last resort for severely affected patients, though is limited by associated morbidities, high cost and the need for specialized clinical care, and is generally not accessible to patients in countries with limited healthcare resources.

About Intellia Therapeutics

Intellia Therapeutics is a leading clinical-stage genome editing company, focused on the development of proprietary, potentially curative therapeutics using the CRISPR/Cas9 system. Intellia believes the CRISPR/Cas9 technology has the potential to transform medicine by both producing therapeutics that permanently edit and/or correct disease-associated genes in the human body with a single treatment course, and creating enhanced engineered cells that can treat oncological and immunological diseases. Intellia’s combination of deep scientific, technical and clinical development experience, along with its leading intellectual property portfolio, puts it in a unique position to unlock broad therapeutic applications of the CRISPR/Cas9 technology and create new classes of therapeutic products. Learn more about Intellia and CRISPR/Cas9 at Follow us on Twitter @intelliatweets.

Intellia Contacts:

Glenn Goddard
Chief Financial Officer
[email protected]

Julie Ferguson
Interim Head, External Affairs & Communications
[email protected]