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

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.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2017
Accession Number
AD1046380

Entities

People

  • Francis J. Miller

Organizations

  • Duke University

Tags

DTIC Thesaurus Topics

  • Acute Respiratory Distress Syndrome
  • Blood Transfusions
  • Cell Line
  • Cells
  • Chemical Synthesis
  • Cytokines
  • Dysfunction
  • Endothelial Cells
  • Health Services
  • Internal Medicine
  • Lung Diseases
  • Medical Personnel
  • Morbidity
  • Nucleic Acids
  • Research Facilities
  • Therapy
  • Wounds And Injuries

Fields of Study

  • Biology
  • Medicine

Readers

  • Immunology and Pathology