MSCs have undergone extensive clinical testing for many diseases and have consistently demonstrated safety. While the immunomodulatory properties of MSCs have been well characterized, adult-tissue -derived MSCs have shown limited therapeutic efficacy, significant variability among samples, and limited proliferative capacity.

Genome-editing endonucleases are currently undergoing early clinical evaluation for the treatment of a wide range of diseases. However, in vivo use of gene-editing endonucleases is limited by the risk of potentially harmful off-target effects.

COL7A1 is a large gene, encompassing 118 exons, several of which are dispensable to protein function. Two exons, exon 73 and 80, are mutational hotspots. Consequently, omitting these exons through alternative splicing may have a great therapeutic effect. The use of antisense oligonucleotides (ASOs) to cause transient skipping of exon 73 and 80 have been shown to restore functional anchoring fibrils in patient-derived fibroblasts and keratinocytes by others.