Artificial transcription factors that modulate nuclear receptors and their therapeutic use

摘要

The present invention comprises polydactyl zinc finger proteins that specifically target a promoter region of a nuclear receptor gene fused to a repressor or activation protein domain, a nuclear localization sequence, and a protein transduction domain It relates to an artificial transcription factor. In particular examples, these promoter regions of the nuclear receptor gene regulate expression of the glucocorticoid receptor, androgen receptor, or estrogen receptor ESR1. Artificial transcription factors directed to glucocorticoid receptors are useful for the treatment of inflammatory processes, diabetes, obesity, coronary artery disease, asthma, celiac disease, and diseases regulated by glucocorticoids such as lupus erythematosus. Artificial transcription factors targeting the androgen receptor are testosterones 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 Useful for the treatment of diseases regulated by Artificial transcription factors that target estrogen receptors are useful in the treatment of various estrogen-regulated diseases such as cancer, cardiovascular disease, osteoporosis, or mood disorders.