ALDATU BIOSCIENCES INC — Department of Health and Human Services SBIR Phase I: NIAID

Description

Lassa virusLASVthe causative agent of Lassa hemorrhagic feverLHFcausesmillion infections anddeaths each yearand further threatens global health security as a potential cause of epidemics and pandemicsRapid and accurate diagnosis is critical to global health effortswith a clear effect on LASV treatmentvaccine developmentand outbreak containmentAs observed in theNigeria outbreakburdensome and time consuming diagnostic protocols delay results reportinge gdays from sample collectionunnecessarily expose healthcare workers to infectionandby delaying diagnosis in LASV negative casespush the healthcare infrastructure beyond its capacityqPCR based molecular assays offer the greatest potential for creating rapid and sensitive LASV diagnostic toolsbut high genetic diversity has precluded a pan lineageuniversal diagnostic that sensitively and specifically detects all clades of LASV with equal performanceMultiple assays targeting different genomic regions are used in the clinic in an attempt to mitigate viral genetic variabilitynecessitating time consumingsequential diagnostic protocolsAldatu s PANDAA technology is a novel platform which enables probe based qPCR for target detection in highly variable genomic regions by simultaneously adapting and amplifying diverse templatesPANDAA uniquely mitigates the presence of target proximal polymorphisms to allow otherwise divergent templates to be detected with consensus fluorescent probes with similar sensitivitiesBuilding off of our team s success in development of PANDAA based assays for SNPs in HIVanother highly polymorphic pathogenwe propose here to leverage the unique capabilities of PANDAA to mitigate lineageassociated genomic variability and develop a rapidpan lineage molecular assay for LASV detectionPreliminary feasibility studies have shown that even our as yet unoptimized PANDAA reagents detect at least five divergent LASV lineages with near equal sensitivityIn this Phase I proposalwe plan to develop and validate an optimized PANDAA LASV assay through the following aimsinitial design of PANDAA LASV reagentsprimers probes and bufferusing optimized in house design workflowsrefinement of PANDAA LASV reagents on divergent genotypes representing all circulating lineagesandanalytical and clinical validation of a PANDAA LASV diagnostic assay prototype with panels to rigorously assess sensitivity and specificitySuccessful development and validation of the first pan lineage PANDAA LASV assay will precede a clinical diagnostic product that could significantly improve LHF diagnosismanagementand outbreak responseeffectively reducing the testing algorithm from two tests to oneThis noveluniversal detection assay could ultimately be deployed in any endemic region on pre existing qPCR equipment in central labsand or integrated into a closedpoint of care system with sample processing to radically improve the LHF diagnostic workflow Rapid and accurate diagnosis of Lassa virusLASVinfection is critical to global health efforts to prevent and manage outbreaks of Lassa hemorrhagic feverLHFwith clear impacts on LHF treatment efficacy and LASV vaccine developmentbut high genetic diversity of circulating LASV lineages has precluded the development of a sensitive molecular diagnostic assay that can be used in all endemic areas and detect all LASV clades with equivalent sensitivityWe propose here to leverage the unique capabilities of Aldatu s qPCR enabling PANDAA technology to mitigate lineage associated genomic variability and develop a rapidpan lineage molecular assay for LASV detectionSuccessful development and validation of the first pan lineage PANDAA LASV assay will precede a clinical diagnostic product that could significantly improve LHF diagnosismanagementand outbreak responseeffectively reducing the molecular diagnostic testing algorithm from two tests to one