Oligonucleotides for upregulating gene expression

Abstract

Over the recent decade oligonucleotides have become an important new class of molecules, allowing therapeutic intervention through targets previously thought 'undruggable'. One of the new avenues opened up by oligonucleotide-based drugs was specific gene upregulation, which, historically, has been difficult to achieve using small-molecule drugs. This article will focus on patents covering this important development in the oligonucleotide field and highlight the different mechanisms through which the oligonucleotide-mediated gene upregulation can work, including inhibition of activity of natural antisense transcripts, interaction with promoter binding sites of noncoding regulatory RNAs, blocking of regulatory and/or miRNA binding sites in 3' UTRs, blocking splice inhibitor/enhancer sites or blocking interactions with polycomb repressive complex 2. Understanding the particular mechanism through which an oligonucleotide drug exerts its effects is highly important in drug development, as it determines the design of the drug molecule.