Protection against lethal marburg virus infection mediated by lipid encapsulated small interfering RNA

Raul Ursic-Bedoya, Chad E. Mire, Marjorie Robbins, Joan B. Geisbert, Adam Judge, Ian MacLachlan, Thomas W. Geisbert

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Background. Marburg virus (MARV) infection causes severe morbidity and mortality in humans and nonhuman primates. Currently, there are no licensed therapeutics available for treating MARV infection. Here, we present the in vitro development and in vivo evaluation of lipid-encapsulated small interfering RNA (siRNA) as a potential therapeutic for the treatment of MARV infection.Methods. The activity of anti-MARV siRNAs was assessed using dual luciferase reporter assays followed by in vitro testing against live virus. Lead candidates were tested in lethal guinea pig models of 3 different MARV strains (Angola, Ci67, Ravn).Results. Treatment resulted in 60%-100% survival of guinea pigs infected with MARV. Although treatment with siRNA targeting other MARV messenger RNA (mRNA) had a beneficial effect, targeting the MARV NP mRNA resulted in the highest survival rates. NP-718m siRNA in lipid nanoparticles provided 100% protection against MARV strains Angola and Ci67, and 60% against Ravn. A cocktail containing NP-718m and NP-143m provided 100% protection against MARV Ravn.Conclusions. These data show protective efficacy against the most pathogenic Angola strain of MARV. Further development of the lipid nanoparticle technology has the potential to yield effective treatments for MARV infection.

Original languageEnglish (US)
Pages (from-to)562-570
Number of pages9
JournalJournal of Infectious Diseases
Volume209
Issue number4
DOIs
StatePublished - Feb 15 2014

Keywords

  • LNP
  • Marburg virus
  • RNAi
  • filovirus
  • guinea pig
  • siRNA
  • therapeutics
  • treatment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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