Abstract: The invention relates to an artificial transcription factor comprising a polydactyl zinc finger protein targeting specifically a gene promoter, engineered to overcome endosomal entrapment after transduction into cells. Such artificial transcription factor comprises a polydactyl zinc finger protein fused to an inhibitory or activatory protein domain, a nuclear localization sequence, a protein transduction domain, and an endosome-specific protease-recognition site. These transducible artificial transcription factors are particularly useful for the treatment of diseases caused or modulated by membrane-bound receptor proteins, nuclear receptor proteins or products of haploinsufficient genes.

Abstract: The invention relates to an artificial transcription factor comprising a polydactyl zinc finger protein targeting specifically a promoter region of a nuclear receptor genefused to an inhibitory or activatory protein domain, a nuclear localization sequence, and a protein transduction domain. In particular examples these promoter regions of a nuclear receptor gene regulate the expression of the glucocorticoid receptor, the androgen receptor, or the estrogen receptor ESR1. Artificial transcription factors directed against the glucocorticoid receptor are useful in the treatment of diseases modulated by glucocorticoids, such as inflammatory processes, diabetes, obesity, coronary artery disease, asthma, celiac disease and lupus erythematosus.

Abstract: The invention relates to an artificial transcription factor comprising a polydactyl zinc finger protein targeting specifically the OPA1 promoter fused to an activatory protein domain, and a nuclear localization sequence. Artificial transcription factors directed against the OPA1 promoter are useful for the treatment of diseases associated with OPA1 haploinsufficiency, such as autosomal dominant optic atrophy, syndromic autosomal dominant optic atrophy plus and normal tension glaucoma.

Abstract: The invention relates to artificial transcription factors comprising polydactyl zinc finger proteins targeting promoters of genes involved in maladapted wound healing in the eye. Such artificial transcription factors are useful for the treatment of fibrocontractive retinal disorders, such asepiretinal gliosis, proliferative vitreoretinopathy, proliferative diabetic retinopathy and epiretinal membrane, and for the treatment of fibroplasia associated with glaucoma surgery.