Comparison of gene expression after intraperitoneal delivery of AAV2 or AAV5 in utero.
Mol Ther
; 8(1): 90-8, 2003 Jul.
Article
en En
| MEDLINE
| ID: mdl-12842432
Correction of diseases may be achieved by delivery of genes to stem cells and developing organ systems. Our previous studies demonstrated life-long expression after in utero injection of adeno-associated virus (AAV) serotype 2 in mice. In the present studies, we compared levels of expression using the elongation factor 1alpha (EF1alpha) or the CMV promoter in AAV2 and AAV5 linked to luciferase via intraperitoneal injection in day 15 fetuses in utero. An additional AAV construct also contained the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). The level and distribution of luciferase expression were assessed by in vivo bioluminescence and luminometric assays. All mice exhibited luciferase expression for >15 months. In vivo, luciferase expression from AAV5 was greater than that produced from AAV2. Vectors containing the CMV promoter produced higher levels of gene expression in all tissues examined compared to EF1alpha-directed vectors. The WPRE increased expression in vitro fourfold and in vivo eightfold. These studies demonstrate that by modifying the promoter and serotype, increases in the efficiency of AAV-directed expression may be achieved. The efficacy of rAAV-mediated gene delivery in utero supports the potential of these vectors for future therapies.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Peritoneo
/
Terapia Genética
/
Dependovirus
/
Feto
Límite:
Animals
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Mol Ther
Asunto de la revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos