A continuous challenge when developing oligonucleotide drugs is enhancing the specificity of the drugs while avoiding adverse effects. We are currently developing an assay (termed LibSeq) to test the regulatory potential and specificity of therapeutic oligonucleotides. In an unbiased background, the assay aims to estimate the potency of regulatory molecules as well as the extent of their off-targets effects. Establishing both on- and off-target potency will assist in developing oligonucleotide drugs which strongly regulate their primary targets, while keeping the impact on other transcripts minimal. We believe this will help increase efficacy and decrease toxicity of oligonucleotide drugs.
Also, it has become apparent that the pervasive importance of miRNAs in cellular development and disease also pertains to the efficacy and toxicity of many traditional drugs, such as chemotherapeutics. For instance, miRNAs target genes, which encode drug metabolizers, and by down-regulating these genes, drug metabolism decreases and serum levels of affected drugs increase. This may in turn have significant downstream consequences for drug efficacy and toxicity. miRNAs are therefore important new players in the field of pharmacogenomics. We have described the scope of miRNA pharmacogenomics (Rukov et al., Trends Mol Med, 2012) and shown that groups of drug related genes vary greatly in their miRNA targeting parameters (Rukov et al., Pharmacogenet Genomics, 2011). Most recently, we have built a web server which facilitates the prediction of miRNA-drug interactions (Rukov et al., Briefings in Bioinformatics, In press)
Both my MSc and PhD were done at the University of Copenhagen, looking at the systems that shape the transcriptome. During my MSc (completed in 2006), I studied the evolution of alternative splicing and its functional significance. I continued this work into my PhD (completed in 2011) where I also studied non-canonical mechanisms of microRNA (miRNA) biogenesis. At a 6 month stay at Tel Aviv University (Noam Shomron lab; in 2010) I furthermore studied the role of miRNAs in regulating drug effects.