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

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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

Fingerprint

Marburgvirus
Virus Diseases
Small Interfering RNA
Lipids
Angola
Nanoparticles
Guinea Pigs
Messenger RNA
Luciferases

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Protection against lethal marburg virus infection mediated by lipid encapsulated small interfering RNA. / Ursic-Bedoya, Raul; Mire, Chad; Robbins, Marjorie; Geisbert, Joan B.; Judge, Adam; MacLachlan, Ian; Geisbert, Thomas.

In: Journal of Infectious Diseases, Vol. 209, No. 4, 15.02.2014, p. 562-570.

Research output: Contribution to journalArticle

Ursic-Bedoya, Raul ; Mire, Chad ; Robbins, Marjorie ; Geisbert, Joan B. ; Judge, Adam ; MacLachlan, Ian ; Geisbert, Thomas. / Protection against lethal marburg virus infection mediated by lipid encapsulated small interfering RNA. In: Journal of Infectious Diseases. 2014 ; Vol. 209, No. 4. pp. 562-570.
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