Summary of Invention
Sickle cell anemia is an inherited monogenic recessive blood disorder characterized primarily by chronic anemia and periodic episodes of pain. The underlying problem involves hemoglobin. In normal red blood cells, hemoglobin molecules carry oxygen from the lungs to body organs and tissues and bring carbon dioxide back to the lungs. In sickle cell anemia, due to a single mutation in the beta globin gene, after hemoglobin molecules give up their oxygen, some may cluster together and form long, rod-like structures.
These sickled red cells cannot squeeze through small blood vessels unlike normal red cells, which are usually smooth and donut-shaped. Instead, they stack up and cause blockages that deprive organs and tissues of oxygen-carrying blood. This process produces periodic episodes of pain and ultimately can damage tissues and vital organs and lead to other serious medical problems. Normal red blood cells live about 120 days in the bloodstream, but sickled red cells die after about 10 to 20 days. Because they cannot be replaced fast enough, the blood is chronically short of red blood cells, a condition called anemia.
The present invention provides a tissue specific inducible expression system capable of co-expressing (i) a therapeutic gene, the gamma globin and (ii) a co-regulated interfering RNA targeting the mutated beta globin gene. In transformed hematopoeitic stem cells, the gamma globin transgene and siRNA expression are under the human beta globin enhancers which control the activity of a human beta globin promoter.
Advantages
- Tissue specific expression of gamma globin and siRNA
- Inducible differentiation stage-specific gene silencing
- Suppression by 95 % of the production if the mutated beta globin
- No immune response induced by siRNA expression
Markets
Incidence of Sickle cell anemia
Sickle cell anemia affects millions throughout the world. It affects around 72,000 people, most of whose ancestors come from Africa. The disease occurs in about 1 in every 500 African-American births and 1 in every 1000 to 1400 Hispanic-American births. About 2 million Americans, or 1 in 12 African Americans, carry the sickle cell trait.
This technology could also be used in cancer by knocking down an oncogene and deliver a tumor suppressor or in other monogenic diseases.
Licensing Field Available
Treatment of monogenic diseases excluding treatment of sickle cell anemia.
Competition
Current treatments available:
- Induction of fetal hemoglobin to inhibit polymer formation.
- Blood transfusion in specific cases, a palliative measure to control pain and infections.
- Bone marrow transplant is the only curative therapy available at the moment. But this therapy is indicated in only a minority of patients, predominantly because of the high risk of the procedure (the drugs needed to make the transplant possible are highly toxic) and difficulty in finding histocompatible donors. Also, bone marrow transplants are much more expensive than other treatments.
- Gene therapies based on globin gene transfer, transplicing ribozymes, oligonucleotides-based gene targeting or artificial transcription factors to derepress endogeneous gamma globin gene expression.
Lead Inventor
Dr. Michel Sadelain
Patent Information
Worldwide rights available. PCT patent application WO2007044627 published 2007-04-19.
References
Contact Information
Viviane Martin, PhD
Tel: 212-639-6181; Fax: 212-717-3439
E-mail: martinv@mskcc.org
