Gene Therapy and RNAi To Treat Sickle Cell Disease

Filed in archive Drugs, Vaccines and Therapeutics , Stem Cells on January 3, 2006

Scientists from the Memorial Sloan-Kettering Cancer Center used a combination of stem cell-based gene therapy and RNA interface technology to genetically reverse sickle cell disease (SCD) in human cells.

Sickle cell disease is a hereditary blood disorder characterized by sickle-shaped red blood cells (instead of disc-shaped) that result to clogged arteries, low blood counts, and subsequently, anemia. Although more common in people of African, Mediterranean, Indian, or Middle Eastern ethnicities, according to the Sickle Cell Disease Association of America (SCDAA), about 1000 babies are born in the US each year. To date, therapy to treat sickle cell anemia involves blood transfusion, which is risky, inconvenient, and pose difficulties in finding compatible donors.

In attempt to correct the gene that results to sickle-shaped red blood cells, the researchers, scientists from the Memorial Sloan-Kettering Cancer Center used a combination of stem cell-based gene therapy and RNA interface technology. A viral vector carrying a therapeutic globin gene harboring an embedded small interfering RNA precursor designed to suppress abnormal hemoglobin formation was introduced in cell cultures of patients who have the disease.

The new gene had two functions -- produce normal hemoglobin and suppress the generation of sickle shaped hemoglobin S. The therapeutic gene was engineered into a lentiviral vector and introduced into hematopoietic stem cells. After the cells received the treatment, they made normal hemoglobin.

"This proved our hypothesis that you can simultaneously add one function and delete another in the same cell and obtain synergistic genetic modifications within a single cell," said Selda Samakoglu, PhD, a member of Dr. Sadelain's laboratory and the study's first author. "In this case, we used the technique to correct sickle cell disease, but it should be broadly applicable to use therapeutically in stem cells or malignant cells."

The results of the study will be published in the January issue of Nature Biotechnology (requires subscription). Abstract is available in PubMed.