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 expression repressors and expression repression systems for modulating expression of a target gene in a cell.

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 modulation of genomic complexes via modulation of non-genomic components such as, non-coding RNAs.

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 disclosure relates generally to methods and compositions for modulating RNA, e.g., using polypeptides comprising Pumilio homology domains.