Gene Therapy for Thalassemia Effective in Mouse Model

Researchers have developed an improved vector for inserting the gene for fetal hemoglobin gamma globin into mice with thalassemia that required only one copy of the gene and provided long-term amelioration of the disorder.

Investigators at St. Jude Children's Research Hospital (Nashville, TN, USA) used a lentivirus vector to insert a single copy of the gamma-globin gene into mouse hematopoietic stem cells (HSCs). The resulting fetal hemoglobin product had previously been shown to effectively relieve symptoms of thalassemia.

The genetic information transported by the virus included the DNA sequence for coding the gamma-globin protein as well as the beta-globin promoter and elements from the beta-globin locus control region (LCR). The transduced HSCs were then transplanted into thalassemic mice.

Results published in the October 15, 2004, issue of Blood revealed that the majority of animals that received HBC transplants expressed high levels of fetal hemoglobin (17%-33%), with an average vector copy number of 1.3. This led to a mean 26 g/l (2.6 g/dl) increase in hemoglobin concentration and enhanced amelioration of other hematologic parameters. These results were significantly better than those obtained during an earlier gene therapy study.

"Our new vector is more dependable, and we need to get only one copy of it into a stem cell to produce significant amounts of fetal hemoglobin,” said senior author Dr. Derek Persons, assistant professor of hematology and oncology at St. Jude Children's Research Hospital. "This combination of using a more effective vector and enriching the population of HSCs that are genetically modified by the gamma-globin gene could one day offer patients with hemoglobin diseases the promise of a cure.”



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