VAJRA INSTRUMENTS, INC. — Department of Health and Human Services SBIR Phase II: 102

Description

Pancreatic ductal adenocarcinomaPDAChas ayear survival rate of less thanThe success in developing therapies for other cancers over the last two decades has not improved the dismal overall survivalOSrate for PDACIt is now becoming increasingly apparent that personalized medicine based on the genetics of a tumor will be essential for developing a treatment strategyThusthere is an urgent need to develop a noninvasivegenetic biomarker based surrogate monitoring test to personalize therapy by rapidly assessing treatment efficacy to make early decisions on therapy strategy and to minimize the andquot cost of failure andquotMeta analysis combining several studies shows that profiling dysregulation of a large panel of circulating microRNAmiRNAsequences in blood will potentially have overspecificity and sensitivity to detect PDAC related alteration due to therapyFor the Phase II studycirculating miRNAs impacted by PDAC have been chosen to validate a blood test technologyThe technology is a quantitative microarray where binding as low aszeptomoles of target molecules to a microspot of immobilized probes will be measured atspecificityzero backgroundattomolar sensitivityand a dynamic range of five orders of magnitudeThe novel detection methodcalled Scanning Electrometer for Electrical Double layerSEEDwill measure local redox on individual microarray spotspatterned on a monolith electrodeto quantify miRNA expression levels without PCR and cDNA conversionThe signal is zero for no bindingi eabsoluteThe binding is by an electrochemical redox enhanced bindingEREBprocess to focus as few ascopies of target molecules to probe molecules immobilized on a Au electrode in andltminA linear semi logarithmic responsesimilar to a standard curve of qPCRis obtained for a target concentration ranging fromtofMAnalysis on plasma from a healthy donor shows a remarkable quantitative correlation between synthetic miRNA in buffer and spiked in plasma ranging fromaM topMAnalysis ofmiRNA sequences on a chip in patient plasma shows multiplexing and a quantitative correlation with qPCRThe two year program to validate the EREB SEED technology will be organized into three specific aimsperform direct miRNA analysis using plasma from a healthy subject that will be spiked with a mixture of synthetic miRNA to evaluate the accuracy of the technology in a biospecimenvalidate the technology on plasma from patient undergoingchemotherapy andradiation therapyto study the efficacy of the therapy by profiling miRNA at different time pointsThe validation will be based on a quantitative figure of merit Profiling microRNAmiRNAcirculating in body fluids has the potential to effectively diagnose diseasessuch as cancer at early stagesand personalize therapyThe proposed study is to validate a quantitative microarray technology that will directly profile dysregulation inmiRNA sequences usingmL of plasma without using PCR and cDNA conversion to measuremolecules atspecificityTwo clinical studies will focus on validation of the technology to quantitatively measure the efficacy of therapy for pancreatic cancer