Comparison of different promoters to improve AAV vector-mediated gene therapy for neuronopathic Gaucher disease.
Hum Mol Genet
; 33(17): 1467-1480, 2024 Aug 18.
Article
en En
| MEDLINE
| ID: mdl-38757200
ABSTRACT
Gaucher Disease (GD) is an inherited metabolic disorder caused by mutations in the GBA1 gene. It can manifest with severe neurodegeneration and visceral pathology. The most acute neuronopathic form (nGD), for which there are no curative therapeutic options, is characterised by devastating neuropathology and death during infancy. In this study, we investigated the therapeutic benefit of systemically delivered AAV9 vectors expressing the human GBA1 gene at two different doses comparing a neuronal-selective promoter with ubiquitous promoters. Our results highlight the importance of a careful evaluation of the promoter sequence used in gene delivery vectors, suggesting a neuron-targeted therapy leading to high levels of enzymatic activity in the brain but lower GCase expression in the viscera, might be the optimal therapeutic strategy for nGD.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Regiones Promotoras Genéticas
/
Dependovirus
/
Enfermedad de Gaucher
/
Vectores Genéticos
/
Glucosilceramidasa
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido