Gene therapy for hemophilia A mice

Hemophilia A is an inherited bleeding disease caused by a lack of the blood clotting protein Factor VIII. It had been hoped that gene therapy would provide a breakthrough in treatment, but the most common gene therapy approach has had little clinical success. However, a team of researchers, at the University of Minnesota Medical School, Minneapolis, has now developed a new approach to target genes specifically to mouse liver sinusoidal endothelial cells (the cells that are the main source of Factor VIII) and used it to provide long-term expression of Factor VIII in hemophilia A mice, markedly reducing their disease. They hope that their data might prove to be a step toward successful human clinical trials in individuals with hemophilia A.

The team, led by Betsy Kren and Clifford Steer, coated nanoparticles with hyaluron so that they targeted liver sinusoidal endothelial cells. To test the efficacy of gene delivery, the hyaluron-coated nanoparticles were engineered to contain a therapeutic gene (Factor VIII) together with a genetic element known as Sleeping Beauty, which helps the therapeutic gene insert into the genome of the targeted cells (i.e, the liver sinusoidal endothelial cells). Even 50 weeks after hemophilia A mice were injected with these nanoparticles, levels of Factor VIII in the blood were the same as in the blood of normal mice and bleeding times were also similar to those of normal mice. The authors hope that this combination of technologies, the cell-specific nanocapsule delivery system and the Sleeping Beauty genetic element, will prove to be a viable gene therapy.

TITLE: Nanocapsule-delivered Sleeping Beauty mediates therapeutic Factor VIII expression in liver sinusoidal endothelial cells of hemophilia A mice

AUTHOR CONTACT:
Betsy T. Kren
University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Phone: (612) 626-4255; Fax: (612) 625-5620; E-mail: krenx001@umn.edu.

Clifford J. Steer
University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Phone: (612) 624-6648; Fax: (612) 625-5620; E-mail: steer001@umn.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=34332