mRNA Therapies for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)

Overview

Dystrophic Epidermolysis Bullosa (DEB) is a disease caused by mutations in the COL7A1 gene, which encodes collagen 7. Many DEB patients have extremely delicate skin, and in the most severe cases, live with painful blisters and open wounds over large areas of their bodies.

Our scientists developed a method for treating dystrophic epidermolysis bullosa by using mRNA to express collagen 7 directly in a patient’s skin.

mRNA Therapies for the Treatment of Dystrophic Epidermolysis Bullosa (DEB) is protected by U.S. Patent Number 9,770,489 (with additional patents pending in the U.S. and in other countries). Of note, the granted patent includes claims that are not limited by specific target sequence, mRNA sequence or chemistry, type of gene-editing protein, or formulation.

Example Applications

Directly express collagen 7 in DEB patient skin
Develop a single product to treat a complex population with hundreds of disease-causing mutations
Treat large areas using a microneedle array

Dose infrequently – collagen 7 has a long in vivo half-life (>30 days)
Combine with Factor’s ToRNAdo™ Nucleic-Acid Delivery System for high efficiency in vivo delivery – proven delivery to human skin in vivo

Representative Data

**Figure 1.** Human skin explant expressing a reporter protein following ToRNAdo™-mediated injection.

Representative Claim

U.S. Pat. No. 9,770,489

An in vivo method for treating dystrophic epidermolysis bullosa, comprising

delivering a synthetic RNA encoding a gene-editing protein that targets a COL7 gene to a patient in need thereof and

delivering a COL7 repair template to the patient,

thereby editing the COL7 gene, wherein:

the synthetic RNA and repair template are delivered to the patient’s keratinocytes by injection to the epidermis and

the gene-editing protein comprises a DNA-binding domain and a nuclease domain and causes a double-strand break in the COL7 gene of the patient’s keratinocytes.