Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study.
Gene Ther
; 10(15): 1225-33, 2003 Aug.
Article
en En
| MEDLINE
| ID: mdl-12858187
The owl monkey (Aotus trivirgatus) has served as the standard non-human primate model of herpes simplex virus-1 (HSV-1) infection because it is highly susceptible to HSV-1 encephalitis. Owl monkeys, however, are expensive, difficult to obtain, and difficult to maintain in captivity, thus greatly hampering the efficiency of preclinical gene therapy trials for brain tumors using HSV-1-based vectors. We have therefore compared the susceptibility of the common marmoset (Callithrix jacchus) with the owl monkey in a model of intracerebral inoculation of wildtype HSV-1 F-strain at increasing titers. The common marmosets consistently succumbed earlier to viral encephalitis than the owl monkeys. The histological evaluation of the common marmoset revealed extensive HSV-1 infection with a concomitant yet less marked inflammatory response compared to the owl monkeys. PCR for HSV-1 demonstrated a similar extra-CNS shedding route in both experimental models. Our findings show that the common marmoset is at least as susceptible to intracerebral HSV-infection as the owl monkey and that it can therefore serve as a valid and reliable experimental model for the important preclinical safety tests of HSV-based therapeutic viral vector constructs in the brain.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Callithrix
/
Herpesvirus Humano 1
/
Encefalitis por Herpes Simple
/
Modelos Animales de Enfermedad
/
Vectores Genéticos
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido