RNA therapeutics

Since the milestones discoveries of catalytic RNAs and RNA interference, the field of RNA therapeutics has emerged for its potential in increasing the range of targets beyond the scope of existing pharmacological drugs. More than 50 RNAs-derived drugs are currently under clinical testing. These are small inhibitory nucleic acids suppressing the expression of disease-causing genes. A similarly large group of diseases may be theoretically cured by augmenting gene expression but no regulatory RNAs that increase protein levels in vivo are available so far. SINEUP transcripts are a new functional class of antisense (AS) lncRNAs whose dominant effect is to promote translation of partially overlapping sense coding mRNAs with no effects on RNA levels. SINEUP activity depends on two functional domains: a 5’ overlap with the coding mRNA that confers target specificity (Target Antisense Region) and an embedded inverted SINEB2 element that functions as activator of translation. Swapping the Target Antisense Region in synthetic SINEUPs may enhance translation of potentially any protein at will, without affecting the transcriptional levels of endogenous target genes. We are currently investigating whether engineered gene-specific SINEUPs may be applied to cure haploinsufficiency disorders.