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Infectious disease

Antisense PMOs protect against Ebola virus

Nature Reviews Drug Discovery volume 5, page 106 (2006)Cite this article

Warfield and colleagues designed antisense phosphorodiamidate morpholino oligomers (PMOs) — oligonucleotide analogues incorporating a phosphorodiamidate link and a morpholine ring — to target EBOV VP24, VP35 and RNA-dependent RNA polymerase (L protein). In contrast to oligonucleotides, PMOs have several drug-like properties — for example, they are non-ionic in character and therefore permeate cells more easily, are resistant to degradation in cells and do not seem to induce an interferon response, all of which make them attractive as potential therapeutic agents.

Promising results with the three EBOV-specific PMOs from a cell-based assay and survival tests in mice and guinea pigs prompted the authors to carry out a small proof-of-concept study in Rhesus macaques. The monkeys were treated with either the VP35-specific PMO or a combination of the VP24, VP35 and L protein PMOs 2 days before exposure to lethal EBOV infection. Whereas monkeys receiving only the VP35-specific PMO succumbed to lethal EBOV infection, 75% of those monkeys receiving the combination treatment survived. Surviving monkeys developed low to moderate viraemia, and testing of their immune response 28 days after infection showed high levels of anti-EBOV antibodies and T-cell responses, indicating a prominent role for the immune system in protection from lethal infection.

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ORIGINAL RESEARCH PAPER

  1. Warfield, K. L. et al. Gene-specific countermeasures against Ebola virus based on antisense phosphorodiamidate morpholino oligomers. PLoS Pathogens 13 Jan 2006 (10.1371/journal.ppat.0020001)

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Authors
  1. Samantha Barton
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Barton, S. Antisense PMOs protect against Ebola virus. Nat Rev Drug Discov 5, 106 (2006). https://doi.org/10.1038/nrd1969

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