Abstract: The present invention provides agents and compositions for modulating expression (e.g., enhanced or reduced expression) of a hepatocyte nuclear factor 4 alpha (HNF4?) gene by targeting an HNF4? expression control region and methods of use thereof for treating an HNF4? associated disorder, e.g., cirrhosis.

Abstract: The present disclosure relates to compositions and methods for reducing expression of MYC gene in a cell. In some embodiments, an expression repressor comprises a targeting moiety that binds a MYC promoter, anchor sequence, or super-enhancer. In some embodiments, the expression repressor comprises an effector moiety that represses transcription or methylates DNA. Systems comprising two expression repressors are also disclosed. The compositions can be used, for example, to treat cancers such as HCC or NSCLC.

Abstract: The present disclosure relates to site-specific disrupting agents for modulating, e.g., decreasing, expression of a target plurality of genes in a cell. In some embodiments, the target plurality of genes comprises pro-inflammatory genes, e.g., CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, and IL-8. In some embodiments, the method comprises using a first site-specific disrupting agent that targets a first anchor sequence and a second site-specific disrupting agents that disrupts a second anchor sequence.

Abstract: The present disclosure relates generally to disruption of genomic complexes associated with fusion genes via a disrupting agent comprising a targeting moiety and/or an effector, e.g., disrupting, moiety. Described herein are experiments directed at identifying target anchor sequences proximal to fusion genes, e.g., fusion oncogenes; targeting the genomic complexes, e.g., CFLs, comprising said target anchor sequences for disruption (e.g., inhibiting their formation and/or destabilizing them) using disrupting agents; and evaluating the effects of disruption on fusion gene expression and other cell (e.g., cancer cell) characteristics (e.g., growth, viability, etc.).

Abstract: The present disclosure relates generally to methods and compositions for modulating frataxin (FXN) expression, e.g., to treat Friedreich ataxia (FRDA).

Abstract: The present invention provides agents and compositions for modulating expression (e.g., enhanced or reduced expression) of a hepatocyte nuclear factor 4 alpha (HNF4a) gene by targeting an HNF4? expression control region and methods of use thereof for treating an HNF4? associated disorder, e.g., cirrhosis.

Abstract: The present invention provides agents and compositions for modulating expression (e.g., enhanced or reduced expression) of an apolipoprotein B (APOB) gene by targeting an APOB expression control region and methods of use thereof for treating an APOB associated disorder, e.g., hypercholesterolemia.