Research Update: “A Bare Bones Approach to Gene Therapy”

Scientists recently discovered a method of gene therapy that successfully enables mice with hemophilia A to produce factor VIII (FVIII) on a long-term basis. The report was published in the February 2007 Journal of Thrombosis and Haemostasis. The new technique takes advantage of the biological structures of viruses that give them an affinity for transferring genes quickly and efficiently into hemophilic host cells.

Qizhen Shi, principal investigator of the study and postdoctoral fellow in hematology/oncology in the Department of Pediatrics at the Medical College of Wisconsin –Milwaukee, and her team of researchers engineered human immunodeficiency viruses (HIV), which were purged of their virulent genetic information and replaced with genetic information programmed to induce FVIII production in hemophilic cells. (Researchers use these transformed viruses, called lentiviruses, as vehicles for gene delivery in gene therapy.)

Next, the scientists “infected” hemophilic bone marrow cells extracted from mice with the 2bF8 lentivirus. The virus was chosen because it takes advantage of the platelet specific IIb promoter (2bF8) to induce FVIII production in hemophilic cells. The altered bone marrow cells were then put back into the hemophilia A mice.

Three months after the hemophilic mice received a regimen of gene therapy, they were subjected to a series of laboratory tests to see if the gene therapy successfully induced their platelets to produce FVIII. Analysis of the mice platelets revealed that they not only produced FVIII for a long period but were also capable of storing it. The hemophilic mice treated with gene therapy did not develop FVIII inhibitory antibodies during the study.

The researchers will continue their work, refining their gene therapy method with the goal of making its use applicable to treating people with hemophilia.

Source: Shi, Q, DA Wilcox, SA Fahs, et al. “Lentivirus-Mediated Platelet-Derived Factor FVIII Gene Therapy in Murine Haemophilia A.” Journal of Thrombosis and Haemostasis. 2007; 5: 352-361.