Autologous hematopoietic stem cells transplantation for expression of collagen vii using the scavenger promoter and sleeping beauty system

Abstract

The monogenic RDEB is a very aggressive disease with no effective treatment yet. As patients suffering exclusively RDEB deficiency of collagen VII, the logical solution would be to provide this protein in the skin/epithelium continously throughout their lives, but how this solution can become a reality? Our proposal is to use hematopoietic stem cells from bone marrow to express the COL7A1 gene under the control of macrophage promoters. Thus, it is expected that the expression of type VII collagen occurs specifically in the skin and epithelia, who suffer from chronic inflammation due to formation of bubbles and attract macrophages to this location, throughout the animal's life and when inflammation is active. For this work become easier to take in future clinical phase, the vectors will be drawn at the base of plasmid vectors with Sleeping Beauty. Due to the absence of an animal model of epidermolysis bullosa in our country, we seek the possibility of developing part of this project at the Institute Thomas Jefferson, United States, where this animal model is well established. (AU)