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Postexposure protection of guinea pigs against a lethal ebola virus challenge is conferred by RNA interference. | LitMetric

AI Article Synopsis

  • Ebola virus (EBOV) causes deadly hemorrhagic fever and currently has no effective antiviral treatments; however, RNA interference using small interfering RNAs (siRNAs) shows promise in inhibiting viral replication.
  • In experiments, guinea pigs treated with siRNAs targeting the polymerase (L) gene of Zaire EBOV demonstrated reduced viremia and improved survival when siRNAs were administered before or shortly after infection.
  • Using stable nucleic acid-lipid particles (SNALPs) to deliver siRNAs proved more effective, achieving complete protection against EBOV when given after infection, indicating a potential for developing effective therapies for EBOV and similar biological threats.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110204PMC
http://dx.doi.org/10.1086/504267DOI Listing

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