Following the sequencing of the mammalian genome, ~20,000 protein-coding genes were identified. At that time 99% of the genome was thought to contain non-functional and repetitive sequences. More recently, researchers utilizing transcriptome profiling approaches have discovered that ~60,000 of these non-functional sequences of the genome are transcribed into long non-coding RNAs (lncRNAs), many of which are functional. Long non-coding RNAs, containing >200 nucleotides, were found to function in various biological processes, such as cell proliferation, differentiation and the regulation of gene expression. Importantly, dysregulation of lncRNA expression has been shown to be associated with the progression of many diseases including cancer, cardiovascular diseases, neurological disorders, diabetes and HIV. Therefore, targeting and reducing specific lncRNAs may result in therapeutic benefit.
In initial work at RXi and in collaboration with Biogazelle, specifically-designed sd-rxRNAs demonstrated potent and target-specific silencing of multiple lncRNAs, including lncRNAs that are strictly localized in the nucleus such as MALAT1. These findings dramatically expand the number of potential sequences RXi is capable of targeting by approximately four fold.