Delivery of Type VII Collagen Gene (COL7A1) for Topical Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Lead Researcher:

Dr Wenxin Wang

Award Date:

1 January 2013

Host Institution:

National University of Ireland, Galway

Scheme:

Health Research Award

Summary:

This proposed research addresses the problem of a lack of wound healing in Recessive Dystrophic Epidermolysis Bullosa (RDEB). The goal of the research is to develop a new topical treatment for RDEB, employing an advanced dressing to locally deliver a critical gene (type VII collagen gene) that is absent in people suffering from RDEB which leads to severe skin blistering. The basis of this gene therapy approach lies in the use of dendritic polymers as a highly efficient delivery system for the therapeutic gene and the use of a modified version of the conventional DNA sequence carriers, called minicircle, which carries the therapeutic gene COL7A1 (MC- COL7A1 ) to effected cells. These polymers will target the delivery of the DNA to fibroblast and keratinocyte cells upon application to patients skin to enhance the entry of the DNA into these cells. The function of the minicircle is to introduce the correct COL7A1 sequence into the pathological host cells and restore normal function in the cell. The additional benefit of using this system is prolonged therapeutic protein expression of type VII collagen. This will result in the expression of the collagen-producing gene missing in RDEB thus improved wound healing. The major outcome from the project will be the development of a method of topical delivery of the collagen-producing gene for (i) improved treatment of skin wounds and (ii) prophylactic application in RDEB. Whilst initial research efforts will focus on wounds of RDEB, the platform technology developed can be expected to be applicable to other wound healing applications. The platform technology will exhibit potential for application in a wide variety of clinical targets.