Accession Number:

ADA467854

Title:

Postexposure Protection of Guinea Pigs against a Lethal Ebola Virus Challenge is Conferred by RNA Interference

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD

Report Date:

2006-06-15

Pagination or Media Count:

11.0

Abstract:

Background. Ebola virus EBOV infection causes a frequently fatal hemorrhagic fever HF that is refractory to treatment with currently available antiviral therapeutics. RNA interference represents a powerful, naturally occurring biological strategy for the inhibition of gene expression and has demonstrated utility in the inhibition of viral replication. Here, we describe the development of a potential therapy for EBOV infection that is based on small interfering RNAs siRNAs. Methods. Four siRNAs targeting the polymerase L gene of the Zaire species of EBOV ZEBOV were either complexed with polyethylenimine PEI or formulated in stable nucleic acid-lipid particles SNALPs. Guinea pigs were treated with these siRNAs either before or after lethal ZEBOV challenge. Results. Treatment of guinea pigs with a pool of the L gene-specific siRNAs delivered by PEI polyplexes reduced plasma viremia levels and partially protected the animals from death when administered shortly before the ZEBOV challenge. Evaluation of the same pool of siRNAs delivered using SNALPs proved that this system was more efficacious, as it completely protected guinea pigs against viremia and death when administered shortly after the ZEBOV challenge. Additional experiments showed that 1 of the 4 siRNAs alone could completely protect guinea pigs from a lethal ZEBOV challenge. Conclusions. Further development of this technology has the potential to yield effective treatments for EBOV HF as well as for diseases caused by other agents that are considered to be biological threats.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE