Benzinga | Mar 10, 2021 07:35AM EST

Intellia Therapeutics Highlights Presentation Of Preclinical Proof Of Concept For CRISPR-Based In Vivo Editing Of Bone Marrow At Keystone eSymposium

- Demonstrates the promise of Intellia's proprietary non-viral delivery system for in vivo genome editing of tissues outside the liver, with applications to inherited blood disorders such as sickle cell disease



- Observed durable, multidose editing of whole bone marrow and hematopoietic stem cells in mouse models at therapeutically relevant levels

CAMBRIDGE, Mass., March 10, 2021 (GLOBE NEWSWIRE) -- 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.