We present preclinical data showing that intradermal injections of genetically corrected patient-derived RDEB fibroblasts using a Good Manufacturing Practices grade self-inactivating COL7A1 retroviral vector reverse the disease phenotype in a xenograft model in nude mice.
Isolated RTMs were then adapted for endogenous trans-splicing in a recessive dystrophic epidermolysis bullosa (RDEB) keratinocyte cell line expressing reduced levels of COL7A1 mRNA.
A -96C-->T mutation in the promoter of the collagen type VII gene (COL7A1) abolishing transcription in a patient affected by recessive dystrophic epidermolysis bullosa.
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin-blistering disorder caused by mutations in the COL7A1 gene that lead to reduced type-VII collagen and defective anchoring fibrils at the dermal-epidermal junction (DEJ).
Identification of two splicing mutations in the collagen type VII gene (COL7A1) of a patient affected by the localisata variant of recessive dystrophic epidermolysis bullosa.
Variations in severity between the different clinical forms of RDEB likely depend on the nature and location of COL7A1 mutations, but observed intrafamilial phenotypic variations suggest additional genetic and/or environmental factors.
Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating inherited skin blistering disease caused by mutations in the COL7A1 gene that encodes type VII collagen (C7), a major structural component of anchoring fibrils at the dermal-epidermal junction (DEJ).
More importantly, LBPAE can effectively deliver minicircle DNA encoding COL7A1 gene (a large and functional gene construct) to substantially upregulate the expression of type VII collagen (C7) in HPDFs, demonstrating its great potential in the treatment of C7-deficiency related genodermatoses such as recessive dystrophic epidermolysis bullosa.
In recessive dystrophic epidermolysis bullosa (RDEB), biallelic mutations of the gene COL7A1, encoding for collagen VII, the main component of anchoring fibrils, lead to a loss of collagen VII in the extracellular matrix (ECM).
Mutations in the human ColVII gene, COL7A1, cause the severe inherited blistering disorder recessive dystrophic epidermolysis bullosa (RDEB) affecting skin and mucosae, associated with a greatly increased risk of skin cancer.
Glycine substitution mutations in COL7A1 not only cause dominant dystrophic epidermolysis bullosa (DDEB), but can also be silent mutations which lead to recessive dystrophic epidermolysis bullosa (RDEB) in combination with additional mutations in the other allele.
Linkage analyses in generalized recessive dystrophic epidermolysis bullosa (RDEB) have implicated the type VII collagen gene (COL7A1), which encodes the major component of anchoring fibrils, and recent identification of COL7A1 mutations has provided direct evidence for COL7A1 defects underlying RDEB.
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease caused by mutations in the COL7A1 gene that result in absent or dysfunctional type VII collagen protein production.
Besides the 730 mutations reported, we identified two novel COL7A1 gene mutations in a Chinese family, which caused recessive dystrophic epidermolysis bullosa (RDEB).
To overcome these limitations, we applied an A•T→G•C adenine base editor (ABE) to correct two different COL7A1 mutations in primary fibroblasts derived from RDEB patients.