Aptalogic, Inc. — Department of Health and Human Services STTR Phase I: NIAID

Description

The diseases caused by dengue virusesDENVmosquito borne members of the family Flaviviridaehave emerged as the most important arthropod borne viral diseases of humansThe frequencygeographical distributionand severity of DENV epidemics have increased dramatically over the past decadeDENV is spread by mosquito species that also harbor Zika virusZIKVand yellow fever virusAlthough these viruses are endemic in tropical countriesthey have also been reported in the southern states of the USA and are likely to move northward as global climate change increases their rangeAbout half of the worldandapos s population is at risk for DENV infection including populations in the United StatesFor examplean outbreak of DENV in Hawaii fromtoinvolvedreported casesOvermillion people globally are estimated to suffer from the symptoms of dengue fever each year and of these at leastdevelop more severe symptoms with a fatality rate that can reachA repeat infection has a higher probability of being fatalEarly symptoms of DENV infection are similar to symptoms caused by many other hemorrhagic viruses including ZIKVEbola and yellow feverCurrent serology cannot distinguish ZIKV and DENV infectionsThe lack of discriminating serology and the similar clinical presentations make it more difficult to rapidly identify the virus causing the symptomswhich delays effective patient treatmentThis is a serious problem in areas where DENV and ZIKV are endemic and it is necessary to know which virus has infected a pregnant womanNucleic acid aptamers function as antibodies with tight and specific recognition of their targetsbut have many advantages over antibodiesparticularly for diagnosticsAdvantages include stability to high temperaturesfacilitating their storage and reusabilitychemical synthesis that limits batch variationand structural changes on binding ligand that enable their integration into many sensor platforms that are capable of rapid responsesAptamers also prefer to interact with regions on a protein target than antibodiesThe goal of this proposal is to develop an aptasensor with nucleic acid aptamers that can distinguish the NSproteins of DENV and ZIKVThe aptamers will be linked to nanoporous anodic aluminum oxideNAAOfor detecting DENV infectionsThe following specific aims are proposedSelect and mature a DNA aptamer that binds DENV NSwith high affinity and specificity and test current ZIKV aptamers for specificity to ZIKV NSover DENV NSIntegrate the aptamers into an NAAO sensor and demonstrate the ability to distinguish DENV and ZIKV NSin the presence of serum proteinsWith successful completion of these aimsthe sensor will be optimized for specificitysignal noise and accuracy in a phase II project to develop it for clinical applicationOur ultimate goal is to develop a multiplexed sensor with aptamers to many hemorrhagic viruses that can be used by clinicians can obtain a rapid readout of the virus responsible for the presented symptoms to enable speedy initiation of the optimal treatment program Dengue virus outbreaks are increasing in frequency throughout the worldincluding in FloridaHawaiiTexas and Puerto Ricoand result in death for up toof victimsEarly and accurate diagnosis is needed but no current serological diagnostics can reliably distinguish between Dengue virus and Zika virusWe propose to develop an aptasensor that can quickly recognize the presence of Dengue NSprotein and distinguish it from the NSprotein of Zika virus