| abstract |
Methods of suppressing or modulating gene expression in a cell using a molecule comprising a nucleic acid binding oligonucleotide region and a expression repressor portion comprising a polypeptide or peptidomimetic or a modifying portion which is a polypeptide or peptidomimetic capable of modulating the covalent modification of nucleic acid or chromatin. The molecule may be a peptide nucleic acid (PNA) construct. Preferably the repressor or modifying portion is a histone deacetylase or a DNA methylase or part of a histone deactylation complex (HDAC), including any one of PLZF, N-COR, SMRT, Sin3, SAP18, SAP30, HDAC, NuRD, MAD1, MAD2, MAD3, MAD4 Rb or E7. The molecule may also include a nuclear localisation signal. Also claimed is the use of such a method to modulate gene expression in plant or animal cells and the production of pharmaceuticals, methods of treatment and methods of designing such modulating molecules. |