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Targeting Extracellular Histones with Novel RNA Biodrugs for the Treatment of Acute Lung Injury

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The University of Iowa Iowa City United States

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Extracellular or circulating histones have been proposed as the causative agent of acute lung injury ALI. The goal of this proposal is to develop a therapeutic to neutralize inactivate circulating histones and prevent the morbidity and mortality associated with multiple organ dysfunctionacute respiratory distress syndrome MODSARDS and ALI that can be easily delivered in combat and field situations. To accomplish this goal, we developed novel bio-reagents RNA aptamers that bind to those histones known to cause MODSARDS and ALI but do not bind to other proteins or cells in blood. The RNA aptamers were evaluated for their ability to inhibit histone-mediate 1. cytotoxicity, 2. platelet aggregation, 3. TLR activation and 4. calcium influx. In this report, we provide evidence for the in vitro efficacy of three individual RNA aptamers KU5, KU7 and KU9. Future efforts will focus on evaluating safety and in vivo efficacy of the aptamers in murine models of ALI. Finally, the levels of circulating histones will also be quantitated in samples from ALI patients.

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Technical Report,15 Sep 2016,14 Sep 2017



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Approved For Public Release;

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