Transforming growth factor beta induced (TGFBI) genomic DNA locus (TGFBI)

The Transforming growth factor beta induced (TGFBI) genomic DNA locus encodes an extracellular matrix protein, keratoepithelin, which is essential for cell-collagen interactions and maintaining corneal transparency (UniProt Q15582). Mutations within this locus are the underlying cause of TGFBI-linked corneal dystrophies, a group of autosomal dominant disorders characterized by the progressive accumulation of insoluble protein deposits in the cornea (PubMed 21810911). These deposits, which can be amyloid or hyaline in nature, lead to significant visual impairment and often require corneal transplantation (PubMed 30314319). Therapeutic strategies targeting the mutant genomic DNA locus focus on allele-specific intervention, such as CRISPR/Cas9-mediated gene editing or siRNA-mediated gene silencing, to selectively reduce the expression of the mutant allele (PubMed 28813138, PubMed 31461344). By preventing the synthesis of the misfolded protein at the genomic or transcript level, these therapies aim to halt disease progression and preserve vision. Current clinical and preclinical efforts are centered on optimizing delivery methods to the corneal stroma and ensuring high specificity to avoid disrupting the wild-type allele (PubMed 33454567).

Other names

BIGH3KeratoepithelinRGD-CAPBeta-ig-h3Corneal dystrophy gene locusTGFBIp

Allele-specific gene disruption, RNA interference (RNAi), Gene silencing, Gene editing