Accession Number : AD1046380


Title :   Targeting Extracellular Histones with Novel RNA Bio drugs for the Treatment of Acute Lung Injury


Descriptive Note : Technical Report,15 Sep 2016,14 Sep 2017


Corporate Author : Duke University Durham United States


Personal Author(s) : Miller, Francis J


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1046380.pdf


Report Date : 01 Oct 2017


Pagination or Media Count : 26


Abstract : 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 dysfunction/acute respiratory distress syndrome (MODS/ARDS) 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 MODS/ARDS 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 vitroefficacy 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.


Descriptors :   wounds and injuries , lung , respiratory system , therapeutics , military medicine , proteins , rna , toxicity , exposure (physiology) , infection , burns


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE