Zinc finger protein composition for the regulation of huntingtin (HTT)

摘要

The present disclosure is in the field of Htt gene expression and regulation of HTT protein levels. Methods and compositions for diagnosing and / or treating Huntington's disease are disclosed herein. In particular, zinc finger protein compositions that regulate Htt expression, such as mutant Htt gene (mHtt) expression and selective suppression of toxic mutant HTT (mHTT) proteins, are provided herein. These compositions and methods selectively suppress over 99% of HD-causing alleles over an 80-fold dose range while preserving over 86% expression of wild-type alleles found in the HD population. .. Expression of other CAG-containing genes is minimally affected, and the artificial transcription factor repressors described herein have been used in culture for at least 9 months or more in mouse brain for more than 100 days. Beyond, it exhibits activity in HD neurons and is well tolerated.