The invention relates to an artificial transcription factor comprising a polydactyl zinc finger protein targeting specifically a promoter region of a nuclear receptor gene fused 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. Artificial transcription factors directed against the androgen receptor are useful in the treatment of diseases modulated by testosterone, such as various cancers, coronary artery disease, metabolic disorders such as obesity or diabetes or mood disorders such as schizophrenia, depression or attention deficit hyperactivity disorder. Artificial transcription factors directed against the estrogen receptor are useful in the treatment of diseases modulated by estrogens, such as various cancers, cardiovascular disease, osteoporosis or mood disorders.本發明係關於一種人工轉錄因子，其包含與抑制性或活化性蛋白質域、核定位序列及蛋白轉導域融合之特異性以核受體基因之啟動子區域為目標之多指鋅指蛋白。在特定實例中，核受體基因之此等啟動子區域調節糖皮質激素受體、雄激素受體或雌激素受體ESR1之表現。針對該糖皮質激素受體之人工轉錄因子適用於治療由糖皮質激素調節之疾病，諸如發炎性過程、糖尿病、肥胖症、冠狀動脈病、哮喘、乳糜瀉及紅斑狼瘡。針對該雄激素受體之人工轉錄因子適用於治療由睪固酮調節之疾病，諸如各種癌症、冠狀動脈病、代謝失調(諸如肥胖症或糖尿病)或情感障礙(諸如精神分裂症、抑鬱症或注意力不足過動症)。針對該雌激素受體之人工轉錄因子適用於治療由雌激素調節之疾病，諸如各種癌症、心血管疾病、骨質疏鬆症或情感障礙。
