Rescue of non-human primates from advanced Sudan ebolavirus infection with lipid encapsulated siRNA.
Nat Microbiol
; 1(10): 16142, 2016 08 22.
Article
em En
| MEDLINE
| ID: mdl-27670117
ABSTRACT
Although significant progress has been made in developing therapeutics against Zaire ebolavirus, these therapies do not protect against other Ebola species such as Sudan ebolavirus (SUDV). Here, we describe an RNA interference therapeutic comprising siRNA targeting the SUDV VP35 gene encapsulated in lipid nanoparticle (LNP) technology with increased potency beyond formulations used in TKM-Ebola clinical trials. Twenty-five rhesus monkeys were challenged with a lethal dose of SUDV. Twenty animals received siRNA-LNP beginning at 1, 2, 3, 4 or 5â
days post-challenge. VP35-targeting siRNA-LNP treatment resulted in up to 100% survival, even when initiated when fever, viraemia and disease signs were evident. Treatment effectively controlled viral replication, mediating up to 4 log10 reductions after dosing. Mirroring clinical findings, a correlation between high viral loads and fatal outcome was observed, emphasizing the importance of stratifying efficacy according to viral load. In summary, strong survival benefit and rapid control of SUDV replication by VP35-targeting LNP confirm its therapeutic potential in combatting this lethal disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença pelo Vírus Ebola
/
RNA Interferente Pequeno
/
Interferência de RNA
/
Lipídeos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
País/Região como assunto:
Africa
Idioma:
En
Revista:
Nat Microbiol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Canadá