Efficient targeting of adenoviral vectors to integrin positive vascular cells utilizing a CAR-cyclic RGD linker protein.
Biochem Biophys Res Commun
; 338(2): 847-54, 2005 Dec 16.
Article
em En
| MEDLINE
| ID: mdl-16259946
ABSTRACT
Vascular smooth muscle (VSMC) and endothelial cells (EC) are particularly resistant to infection by type 5 adenovirus (Ad) vectors. To overcome this limitation and target Ad vectors to ubiquitously expressed alpha(V)beta(3/5) integrins, we have generated a linker protein consisting of the extracellular domain of the coxsackie adenovirus receptor (CAR) connected via avidin to a biotinylated cyclic (c) RGD peptide. After optimization of CAR to cRGD and to Ad coupling, infection of mouse heart endothelial cells (H5V) could be augmented significantly, as demonstrated by 600-fold increased transgene expression levels. In EOMAs, a hemangioendothelioma-derived cell line, the fraction of infected cells was enhanced 4- to 6-fold. Furthermore, the fraction of infected primary mouse VSMC was increased from virtually 0% to 25%. Finally, in human umbilical vein endothelial cells, the number of GFP positive cells was enhanced from 2% to 75%. In conclusion, CAR-cRGD is a versatile and highly efficient construct to target Ad vectors to both transformed and primary VSMC and EC.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Transfecção
/
Integrinas
/
Adenoviridae
/
Receptores de Vitronectina
/
Miócitos de Músculo Liso
/
Integrina alfaVbeta3
/
Músculo Liso Vascular
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Holanda