MicroRNAs (miRNAs) are small (~23 nucleotide) non-coding RNAs that have recently emerged as important regulators of ~65% of all protein coding genes in our genome^1-4. They have the unique ability to carry out sequence specific silencing of multiple genes in a pathway. Based on the central and pivotal position miRNAs occupy in the RNA revolution miRNA-based therapies are being developed by an increasing number of pharmaceutical companies (GlaxoSmithKline, Regulus Therapeutics, Isis and Alnylam, Santaris and Novartis) for an increasing number of diseases ranging from heart disease, cancer and asthma. These efforts herald a new era in which the integration of miRNAs into existing therapies is hoped to significantly increase the efficacy and specificity treatments. However, effective delivery of miRNAs into appropriate cells without significant cytotoxicity is still a problem.  Recently, successful delivery of siRNA (~22 nucleotide)-conjugated gold nanoparticles into cells and efficient knock-down target genes without significant cytotoxicity was reported⁵. Using microRNA microarrays we have identified predicted microRNA-mRNA associations in multiple myeloma (MM) cells resistant to arsenic trioxide (ATO, As2O3) treatment. In the proposed work we aim to validate these miRNA-mRNA associations using Next Generation Sequencing (NGS) to develop prognostic markers and therapeutic targets for ATO-resistance (ATO-R). Amine-functionalized microRNA conjugated nanoparticles will be developed as biosensors for the ATO-R MM signature and therapeutic agents targeting and disrupting specific miRNA-mRNA associations supporting ATO-R MM.