Adenovirus-mediated gene transfer into monocyte-derived macrophages of patients with X-linked chronic granulomatous disease: ex vivo correction of deficient respiratory burst.
Gene Ther
; 4(6): 524-32, 1997 Jun.
Article
en En
| MEDLINE
| ID: mdl-9231068
ABSTRACT
The underlying cause of X-linked chronic granulomatous disease (X-CGD) is mutations in the gp91phox coding gene. Gp91phox is the larger subunit of the cytochrome b558, the membrane-bound terminal redox centre of the respiratory burst oxidase (NADPH oxidase). We have constructed a recombinant adenovirus which contains a functional copy of the human gp91phox cDNA under the control of the cytomegalovirus (CMV) enhancer/promoter region. This vector was used to infect monocyte-derived macrophages of gp91phox-deficient CGD patients. Expression of the gp91phox transgene resulted in ex vivo reconstitution of the respiratory burst activity. Nitroblue-tetrazolium staining indicated that 74% of the patient cells could be phenotypically corrected when compared with a corresponding control culture of normal monocyte-derived macrophages. Adenoviral gene transfer may become a promising tool and gain therapeutical potential by the targeting of autologous monocytes. Genetically corrected autologous monocytes may be used for supportive treatment of X-CGD patients to overcome acute life-threatening infections. Establishment of adenovirus-mediated reconstitution of gp91phox-deficient monocytes therefore represents a first step towards the development of a clinically applicable supportive transient somatic gene therapy in CGD.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Adenoviridae
/
Estallido Respiratorio
/
Técnicas de Transferencia de Gen
/
Enfermedad Granulomatosa Crónica
/
Macrófagos
Límite:
Humans
Idioma:
En
Revista:
Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
1997
Tipo del documento:
Article
País de afiliación:
Suiza