Paratus Diagnostics — Department of Health and Human Services STTR Phase I: NIAID

Description

Project Summary Abstract Seasonal influenza has an annual global incidence of up to in adults and up to in children About to million infections result in severe disease while somewhere between a quarter and a half million cases are fatal Antiviral drugs can lessen the severity and reduce mortality when administered within h of onset of symptoms Hence sensitive and specific point of care POC diagnostic tools especially those that can be used at home can be invaluable in expediting appropriate therapy and mitigating viral spread While TaqMan real time reverse transcriptase polymerase chain reaction RT PCR and viral culture continue to be the diagnostic gold standards several rapid POC influenza diagnostic technologies have been commercialized Although results are available within min most of these tests have poor sensitivity compared to gold standards Rapid tests based on isothermal nucleic acid amplification Alere i influenza A and B test have also recently become available and while they are very specific and sensitive they can be too expensive for widespread POC use $ to $ per test and requiring the Alere i instrument that itself costs about $ To reduce testing cost and make nucleic acid diagnostics more widely available for at home testing we propose to develop a one pot robust and cheap POC test that can distinguish influenza A and B viruses Key to this technology is viral RNA amplification by loop mediated isothermal amplification LAMP and conversion of the resulting nucleic acid amplicons into glucose for readout via widely available over the counter glucometers Overall in a partnership between Paratus Diagnostics and the Ellington lab at the University of Texas at Austin we will develop a Paratus Consumable Cartridge PCC that will serve as an all in one device that extracts amplifies and transduces pathogen genetic signatures from patient samples to glucometers for readout and is projected to cost about $ device In particular we will develop reverse transcription RT LAMP assays specific for the influenza A and B virus matrix genes Aim Objective and transduce the amplicons into glucose via our novel patent pending sequence specific oligonucleotide strand displacement OSD reporters Aim Objective We will automate the molecular assay on the PCC Aim Objective and using biological samples perfect field appropriate sample extraction procedures requiring only intuitive user input Aim Objective Diagnostic utility of the PCC and the molecular assay will be demonstrated by comparing its robustness and its positive and negative predictive values with those of TaqMan real time RT PCR when challenged with blinded surrogate clinical samples Aim Objective These data will position the PCC based POC diagnostic for further validation with clinical samples and eventually field trials Project Narrative Cheap and portable influenza diagnostics will incentivize widespread use and thereby potentiate effective treatment and better head off pandemics Our proposed isothermal amplification assays will ultimately transduce only a few copies of viruses in unaltered biospecimens into the presence of glucose which can in turn be read via commercially available hand held glucometers If successful nucleic acid amplification assays for influenza can readily be reconfigured for other infectious and communicable diseases