TARGETED DEGRADATION OF THE ONCOGENIC MICRORNA 17-92 CLUSTER BY STRUCTURE-TARGETING LIGANDS

摘要

Embodiments of methods are disclosed for inhibiting, regulating and/or otherwise affecting or managing the pri-miR- 17-92 cluster, and certain pre-miRNA's embedded in the cluster as well as the pre-miRNA's themselves as isolated forms, as members of a library, present in oncogenic and/or polycystic cell lines and/or that are present in breast cancer, prostate cancer and/or polycystic kidney disease in animals or humans, or present in any other disease in which the pri-miR-17-92 cluster and the certain pre-miRNAs within in it cause or contribute to disease. The methods utilize compounds that target the structural feature or features of the pri-miR-17-92 cluster and/or the certain pre-miRNA's. The pre- miRNA's are members of the pre-miRNA-X group which includes one or more of pre-miR- 17, pre- miR-18a, pre-miR-19a, pre-miR-19b-1, pre-miR-20a, and pre-miR-92a-1 or any combination thereof. The compounds incorporate a dimeric formula of a binding moiety for the certain pre-miRNA-X's. The binding moiety can bind or complex with structural feature(s) of the certain pre-miRNA-X's without specificity for the particular nucleotide sequence of the structural features. The binding moiety nevertheless is selective for the certain structural feature(s) so that it does not bind with other pre-miRNA's not having the certain structural feature(s).