MicroRNA-Based Radiation Biodosimeter (MiRAD)

DESCRIPTION provided by applicant The broad long term goal of this project is to develop an optically based radiation biodosimeter that rapidly minutes measures changes in serological microRNA miRNA biomarkers to predict acute radiation syndrome ARS MicroRNAs miRNAs are short base non coding RNA strands that control a host of biological processes through regulation of protein expression Exposure to radiation has been shown to alter expression of a miRNA panels linked with ARS thereby establishing that serum could be used as a predictive assay for ARS To measure changes in these miRNA radiation biomarkers we will develop a MicroRNA based Radiation Biodosimeter MiRAD system which combines automated magnetic bead based screening for miRNA targets with Amplified Reflectometric Interference Analysis ARIA a patented ChromoLogic technology for highly sensitive and specific quantification of s of miRNA radiation biomarkers in parallel In preliminary studies we have demonstrated the novel concept of the device and its ability to accurately measure subfemtomolar concentrations of miRNA in ovarian cancer serum samples x less than current RNA quantification platforms such as RT PCR Our preliminary studies using rodent plasma also have identified panel of miRNAs with dose and time dependent response to whole body irradiation WBI in a dose range relevant to medical triage in case of a radiological event The hypotheses we seek to validate under the proposed proof of concept study are the miRNA panel identified in a murine model through analysis of plasma can be used to measure WBI dose in a clinical setting a similar miRNA panel can be used to measure WBI dose in nonhuman primates and humans the resulting identification of a unique and dose responsive combination of miRNA markers will result in a rapid POC blood based microchip assay for anticipating ARS within the first week of exposure thereby guiding the allocation of exposed subjects for timely medical intervention PUBLIC HEALTH RELEVANCE A critical need exists in the area of radiation countermeasures to properly diagnose and treat victims of a nuclear or radiological incident who are at risk for developing acute radiation syndrome ARS ChromoLogic proposes to develop the MiRAD technology which will measure changes in microRNA biomarkers in a patientandapos s blood for diagnosis of ARS The creation of this predictive diagnostic system will result in earlie and improved treatment allocation reduced mortality and provide a means of predicting toxicities in patients undergoing radiotherapy especially in situations where over or under dosing remain a concern