Phase 2: NIS proteins with altered anion specificity

Abstract Imanis is a reporter gene imaging company which has chosen to emphasize NIS technology over other reporter proteinsNIS is the sodium iodide symporterwhich mediates the uptake and concentration of iodide in the thyroid glandproviding the basis for diagnostic thyroid radioimaging and radioiodine therapyNIS reporter gene technology allows accuratesensitivehigh resolution visualization of NIS modified cellsgenes and viruses in living mammalsmouse to humanAdditionallyNIS lacks immunogenicityNIS is a self proteinand is harmless to targeted tissuesallowing for longitudinal imaging throughout the lifespan of the animalNIS expressing cells and tissues can be imaged with a variety of readily available anionic radiotracers such asIIIBFtetraflouoroborateandmTcOpertechnetateNIS expressing cells can also be destroyed using betaor alphaparticle emitting anionsIReOperrhenateorAstatideThe overarching goal of this SBIR application is to generate NIS variants that can be used to enhance the sensitivity of NIS reporter gene imaging to monitor virusgene and cell therapiesDuring Phase I part of the awardwe screened a large number of NIS mutationsWe have subsequently identified and generated NIS mutants that demonstrated superior isotope uptake and met the agreed milestone of the Phase I grantIn this Phase II applicationwe will build on those findings and will developvalidate and market the next generation of NIS reporter genes tailored specifically for optimal performance withmTcOand BFradiotracersThese NIS variants will be commercially developed to provide the scientific and medical community with vastly improved in vivo reporter gene imaging solutions