Current Clinical Targets
The Skin and RDEB
The skin is the largest organ of the body and is extremely dynamic, responsible for a multitude of body functions. All layers of the skin work in unison to provide both structural integrity and strength, as well as flexibility. Collagens comprise a family of proteins which are major components of the skin and connective tissues.
Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare, inherited debilitating skin fragility disorder caused by mutations in the COL7A1 gene which codes for collagen VII, a crucial protein which gives structural integrity to the skin.
Mutations in the COL7A1 gene lead to a non-functional collagen VII protein which is a major component of the anchoring fibrils, which act like “velcro” to adhere the epidermis to the underlying dermis.
A lack of functional Collagen VII leaves the skin extremely fragile, resulting in severe blistering and erosions of the skin throughout the body followed by scarring and fibrosis.
No definitive treatments have been established to date for RDEB with the main principle of care focused on wound management, infection control and pain alleviation. We at Branca Bunús are currently developing BrB 101 for the treatment of RDEB, a gene therapy targeted to remove disease causing mutations in the COL7A1 gene and restoring functional Collagen VII to patients skin.
Collagen VII forms the main component of anchoring fibrils which connect the dermis to the epidermis. RDEB sufferers display damaged or absent anchoring fibrils which causes separation of the skin layers and blister formation.
BrB-101 for Recessive Dystrophic Epidermolysis Bullosa
BrB-101 is our lead product candidate that is targeted to treat and excise disease causing mutations in exon 80 of the COL7A1 gene, leading to a restoration of patients own Collagen VII protein. BrB-101 uses our patented polymer based gene delivery platform technology to carry a CRISPR medicine designed to permanently remove the COL7A1 mutations in exon 80, directly to the skin of suffering patients. This non-invasive approach can restore functional Collagen VII production and thus anchoring fibril formation and structural integrity to patients skin. This non-viral gene therapy is applied topically to open RDEB wounds.
Exon 80 has been identified as a frequent site of recurring mutations that give rise to RDEB.
PAM target sequences adjacent to the mutation site enables CRISPR-Cas recognition for binding.
BrB 101 carrying CRISPR-Cas targeted to PAM sequences adjacent to Exon 80 mutations in COL7A1 gene.
CRISPR-Cas cuts target DNA resulting in deletion of mutation containing Exon 80.
COL7A1 gene is repaired leading to a restoration of Collagen VII production.