Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers

PLoS Pathogens

Robert Blouch¹  Patrick L Iversen¹  David A Stein¹  Kelly L Warfield²  Donald K Nichols²  M. Javad Aman²  Dana L Swenson²  Gene G Olinger²  William D Pratt²  Sina Bavari² 

[1] AVI BioPharma, Corvallis, Oregon, United States of America;US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America

关键词: Monkeys;    Guinea pigs;    Viral replication;    Primates;    Rodents;    Ebola virus;    Immune response;    Protein translation;   

DOI  :  10.1371/journal.ppat.0020001

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The filoviruses Marburg virus and Ebola virus (EBOV) quickly outpace host immune responses and cause hemorrhagic fever, resulting in case fatality rates as high as 90% in humans and nearly 100% in nonhuman primates. The development of an effective therapeutic for EBOV is a daunting public health challenge and is hampered by a paucity of knowledge regarding filovirus pathogenesis. This report describes a successful strategy for interfering with EBOV infection using antisense phosphorodiamidate morpholino oligomers (PMOs). A combination of EBOV-specific PMOs targeting sequences of viral mRNAs for the viral proteins (VPs) VP24, VP35, and RNA polymerase L protected rodents in both pre- and post-exposure therapeutic regimens. In a prophylactic proof-of-principal trial, the PMOs also protected 75% of rhesus macaques from lethal EBOV infection. The work described here may contribute to development of designer, “druggable” countermeasures for filoviruses and other microbial pathogens.

【 授权许可】

CC BY