In vivo gene editing for genodermatoses

Grantee: Thomas Kocher, Postdoc, EB House Austria, Salzburg

Amount: DKK 1,389,845

Grant category: Research grants in open competition

Year: 2020

Geography: Austria

The goal of this project is to evaluate the translational and therapeutic potential of two in vivo CRISPR/Cas9 delivery methods. CRISPR/Cas9 is a gene-editing technology that enables researchers to edit parts of the genome by removing, adding or altering sections of a specific DNA sequence. Although CRISPR/Cas-based technologies hold great promise as genome editing tools in many genetic diseases, its clinical application, especially in genodermatoses, remains a big challenge.

To challenge this hurdle, CRISPR/Cas9 molecules will be delivered into the skin of a suitable animal model via two application methods: laser microporation and gene gun bombardment. The first method uses a laser to make micropores into the skin to allow the CRISPR/Cas9 constructs to enter the outer skin barrier and subsequently the target skin cells. The second method uses a “gene gun”, where gold particles covered with CRISPR/Cas9 constructs are shot directly into the skin/cells.

These constructs can then restore genetic defects in e.g. epidermolysis bullosa (EB) – a genetic condition that results in easy blistering of the skin and mucous membranes – which is used in this project as a model, and potentially cure the disease.

The project will investigate the potential of these two delivery methods in a mouse model using grafted human skin equivalents from expanded recessive dystrophic epidermolysis bullosa (RDEB) patient-derived fibroblasts and keratinocytes. If either delivery method proves efficient, it may hold the potential for development of future treatments, or even cure, of genetic skin diseases.