Lipid nanoparticle siRNA treatment of Ebola virus Makona infected nonhuman primates

Abstract

The current outbreak of Ebola virus (EBOV) in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled ¹ . Several postexposure interventions have been employed under compassionate use to treat a number of patients repatriated to Europe and the United States ² . However, the in vivo efficacy of these interventions against the new outbreak strain of EBOV is unknown. Here, we show that lipid nanoparticle (LNP)-encapsulated siRNAs rapidly adapted to target the Makona outbreak strain of EBOV are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days postexposure while animals were viremic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal hematology, blood chemistry, and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered while the untreated control animals succumbed. These results represent the first successful demonstration of therapeutic anti-EBOV efficacy against the new outbreak strain in nonhuman primates (NHPs) and highlight the rapid development of LNP-delivered siRNA as a countermeasure against this highly lethal human disease.