BME PhD Prospectus Defense - Justin Rosenbohm


BME PhD Prospectus Defense - Justin Rosenbohm


Title: “A semiquantitative ligation-based assay for point-of-care HIV viral load monitoring”

Committee: Catherine Klapperich, PhD – BU BME (Advisor, Chair) Mario Cabodi, PhD – BU BME James Galagan, PhD – BU BME Nira Pollock, MD/PhD – HMS Medicine and Pathology; BIDMC Division of Infectious Diseases

Abstract: Of the 37 million individuals globally living with HIV infection, 21.7 million individuals are currently receiving antiretroviral therapy (ART). ART has been shown to suppress HIV viral loads (VL) and improve outcomes for HIV positive individuals. In order to ensure that HIV positive patients respond to ART as expected, it is necessary to routinely measure VL. While gold standard quantitative HIV VL diagnostics are sensitive and specific, they are expensive and require specialized equipment for thermocycling and fluorescence measurement. While well suited for centralized laboratory testing facilities, current diagnostics cannot be utilized effectively in remote and low-resourced settings. Here, we propose to develop a novel technique for semiquantitative detection of nucleic acids and to apply this technique to develop a low-cost, minimally instrumented assay for HIV VL monitoring that can be used at the point-of-care. Our approach implements enzymatic ligation of oligonucleotide probes on HIV RNA to generate a mixed population of HIV specific ligation products with a controllable distribution. As HIV RNA concentration increases, more of these ligation products can be detected using nucleic acid amplification; the result is a single assay with multiple quantification thresholds. We will demonstrate this concept first using PCR-based amplification and subsequently develop an isothermal assay to eliminate dependence on thermocycling equipment. The assay will be made compatible with a lateral flow immunoassay enabling a simple, visual readout; providing a measure of VL at multiple clinically relevant thresholds. We will explore compatibility of the assay with paper substrates and blood-based samples for future integration into a self-contained disposable diagnostic platform.


9:30am on Tuesday, March 19th 2019


44 Cummington Mall, room 705


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