Gene based therapies to restore normal hemoglobin production and function in patients with hereditary anemia

Technology Overview

Christopher LuxHeritable anemia presents an array of chronic symptoms that in many instances arise shortly after birth and persist throughout a patient’s life. Beyond the direct morbidity associated with chronic anemia, the use of regular blood transfusions can lead to a host of other complications, including iron aggregation throughout the body that can produce serious complications of the heart, liver, and hormone production. More permanent treatments involving bone marrow transplants can reduce or eliminate the need for blood transfusions, but come with their own possible complications including secondary infections and eventual sensitization and rejection of the transplant tissue.

Dr. Christopher Lux has a strong clinical understanding and first-hand experience with pediatric hematology and oncology, with a special focus on two hemoglobinopathies, sickle cell disease and beta thalassemia, that arise from hemoglobin gene mutations. The basis of Dr. Lux’s research is to develop more effective and permanent treatment options for patients with heritable anemia through targeted hematopoietic stem-cell reprogramming. The approach Dr. Lux’s research group employs involves restoring hemoglobin function through targeted gene editing with tools such as targeted endonucleases including TALENs and the CRISPR/Cas9 system. While the ability to selectively edit and restore normal hemoglobin function and production levels is Dr. Lux’s ultimate goal, he has demonstrated success in producing targeted gene insertions and deletions that can increase expression of fetal hemoglobin, ameliorating disease symptoms despite the continuing presence of the underlying pathology.

In his efforts to validate the efficacy of fetal hemoglobin as a therapeutic target, Dr. Lux has developed a range of endonucleases capable of targeting the gamma hemoglobin locus, which has been implicated with producing fetal hemoglobin. These endonucleases include TALENs, AAV delivered CRISPR guides, and a chemically modified mRNA guide that can be delivered without a virus. Dr. Lux has already demonstrated the efficacy of these techniques by modifying stem cells in several animal models, using both xenografts and native tissue to draw homology with human pathologies.

The combination of late stage pre-clinical research and direct patient access place Dr. Lux in an excellent position to offer collaborative opportunities to partners interested in developing gene based therapies for hemoglobinopathies. Diseases in this field have lifelong implications, and advances of the technology used by Dr. Lux could be applied to a broad range of patient groups.

Stage of Development

  • Pre-clinical in vivo
  • Pre-clinical in vitro

Partnering Opportunities

  • Collaborative research and development opportunity
  • Sponsored research agreement
  • Consultation agreement
  • Clinical trial

Publication

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To learn more about partnering with Seattle Children’s Research Institute on this or other projects, please contact:

Dr. Elizabeth Aylward, Director
Office of Science-Industry Partnerships
Seattle Children's Research Institute
2001 8th Ave., M/S CW8-5
Seattle, WA 98121
Email
206-844-1065