Although significant progress has been made in the development of therapeutics against Ebola virus (EBOV), we sought to expand upon existing strategies and combine an RNAi-based intervention with the approved VSV-EBOV vaccine to conjointly treat and vaccinate patients during an outbreak. We constructed VSV-EBOV vectors expressing artificial miRNAs (amiRNAs) targeting sequences of EBOV proteins. In vitro experiments demonstrated a robust decrease in EBOV replication using a minigenome system and infectious virus. For in vivo evaluation, MA-EBOV-infected CD-1 mice were treated 24 hours after infection with a single dose of the VSV-EBOV-amiRNA constructs. We observed no difference in disease progression or survival compared to the control-treated mice. In summary, while amiRNAs decrease viral replication in vitro, the effect is not sufficient to protect mice from lethal disease, and this therapeutic approach requires further optimization.
Keywords: Ebola virus disease; Filovirus; RNAi; amiRNA; animal model; post-exposure prophylaxis; vesicular stomatitis virus.
Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.