APTADIR

Aberrant methylation by DNA methyltransferase 1 (DNMT1) of certain genes may cause abnormal cell development and lead to disease. Current therapies targeted to inhibit DNMT1 have short term results, major side effects – toxicity, and are not gene specific. The platforms we have developed stems from the discovery by Di Ruscio et al that specific RNAs prevent DNA methylation by binding to and inhibiting DNMT1, thereby leading to changes in locus-specific DNA methylation and, ultimately gene expression. This discovery led to the development of an RNA-based platform enabling selective inhibition of DNMT1 in a global and locus specific modality.  For global inhibition, potent sequestration of DNMT1 without cell toxicity as of commercially available drugs was achieved using modified short RNA oligonucleotides (aptaDiR). For locus specific inhibition the platform was implemented by fusing the aptaDiR with a gene-specific sequence (captaDiR) that allows high level of specificity within the targeted locus.