Selection of optimal combinations of target genes for therapeutic multi-gene silencing based on miRNA co-regulation.

ABSTRACT

Therapeutic gene silencing is a promising approach for treatment of cancer. Despite substantial efforts, however, only few such therapeutic methods have been clinically tested. The heterogeneity in gene expression profiles among malignant tissues and the dynamic control of gene expression in individual tumors makes identifying universal and effective targets a challenge. Further development of gene silencing therapy requires new approaches to comprehend and manage gene expression in cancer cells. In this study, we proposed and evaluated experimentally a new approach to design multi-gene silencing therapy. Using a simplified model of gene expression control, we show that genes commonly regulated by the same microRNA represent optimal combinations of targets for small hairpin RNA/small interfering RNA-based gene silencing. The proposed method of target gene selection and co-silencing can be explored as an algorithm for personalized cancer gene therapy.