title: An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells.
abstract: Small noncoding antisense RNAs (sasRNAs) guide epigenetic silencing complexes to target loci in human cells and modulate gene transcription. When these targeted loci are situated within a promoter, long-term, stable epigenetic silencing of transcription can occur. Recent studies suggest that there exists an endogenous form of such epigenetic regulation in human cells involving long noncoding RNAs. In this article, we present and validate an algorithm for the generation of highly effective sasRNAs that can mimic the endogenous noncoding RNAs involved in the epigenetic regulation of gene expression. We validate this algorithm by targeting several oncogenes including AKT-1, c-MYC, K-RAS, and H-RAS. We also target a long antisense RNA that mediates the epigenetic repression of the tumor suppressor gene DUSP6, silenced in pancreatic cancer. An algorithm that can efficiently design small noncoding RNAs for the epigenetic transcriptional silencing or activation of specific genes has potential therapeutic and experimental applications.Molecular Therapy-Nucleic Acids (2013) 2, e104; doi:10.1038/mtna.2013.33; published online 9 July 2013.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Ackley
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lenox
authors.forename: Kenneth
authors.initials: K
authors.lastname: Stapleton
authors.forename: Stuart
authors.initials: S
authors.lastname: Knowling
authors.forename: Tim
authors.initials: T
authors.lastname: Lu
authors.forename: Kenny S
authors.initials: KS
authors.lastname: Sabir
authors.forename: Peter K
authors.initials: PK
authors.lastname: Vogt
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Morris