Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor.
Blood
; 107(12): 4728-36, 2006 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-16478886
Von Willebrand disease (VWD) is an inherited bleeding disorder, caused by quantitative (type 1 and 3) or qualitative (type 2) defects in von Willebrand factor (VWF). Gene therapy is an appealing strategy for treatment of VWD because it is caused by a single gene defect and because VWF is secreted into the circulation, obviating the need for targeting specific organs or tissues. However, development of gene therapy for VWD has been hampered by the considerable length of the VWF cDNA (8.4 kb [kilobase]) and the inherent complexity of the VWF protein that requires extensive posttranslational processing. In this study, a gene-based approach for VWD was developed using lentiviral transduction of blood-outgrowth endothelial cells (BOECs) to express functional VWF. A lentiviral vector encoding complete human VWF was used to transduce BOECs isolated from type 3 VWD dogs resulting in high-transduction efficiencies (95.6% +/- 2.2%). Transduced VWD BOECs efficiently expressed functional vector-encoded VWF (4.6 +/- 0.4 U/24 hour per 10(6) cells), with normal binding to GPIbalpha and collagen and synthesis of a broad range of multimers resulting in phenotypic correction of these cells. These results indicate for the first time that gene therapy of type 3 VWD is feasible and that BOECs are attractive target cells for this purpose.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades de von Willebrand
/
Factor de von Willebrand
/
Terapia Genética
/
Células Endoteliales
Tipo de estudio:
Qualitative_research
Límite:
Animals
Idioma:
En
Revista:
Blood
Año:
2006
Tipo del documento:
Article
País de afiliación:
Bélgica
Pais de publicación:
Estados Unidos