Treatment of highly pathogenic filovirus infections using advanced antisense technology

Filoviruses, comprised of the Ebola viruses (EBOV) and Marburg virus (MARV), are highly pathogenic agents with human case fatality rates up to 90%. Periodic filovirus outbreaks occur in endemic regions of subSaharan Africa, and a new pathogenic EBOV species was discovered as recently as 2008, following an outbreak in Uganda. Additionally, these viruses are considered Category A biodefense pathogens. There exists an urgent need to develop effective antiviral therapeutics and vaccines to protect both civilian and military populations at risk of exposure. Our aim was to identify and develop effective antisense-based therapeutics for treatment of filovirus infections. We have previously shown that synthetic antisense phosphorodiamidate morpholino oligomers (PMOs), which target EBOV-specific transcripts, confer partial protection to infected rodents and rhesus macaques. In this report, we describe the efficacy of a new class of positively charged PMOs (PMO+). Methods Using established rodent models of EBOV and MARV infections, we screened virus-specific PMO+ agents to identify combinations capable of protecting against lethal challenge. Efficacious PMO+ combinations were further evaluated in non-human primate models of filovirus infection. Results