Improved gene transfer selectivity to hepatocarcinoma cells by retrovirus vector displaying single-chain variable fragment antibody against c-Met.
Cancer Gene Ther
; 10(11): 840-9, 2003 Nov.
Article
en En
| MEDLINE
| ID: mdl-14605670
ABSTRACT
Engineered retroviruses are widely used vectors for cancer gene therapy approaches. However, the ability to target cells of therapeutic interest while controlling the expression of the transferred genes would improve both the efficiency and the safety of viral vectors. In this study, we investigated the ability of a retroviral amphotropic envelope displaying single-chain variable-fragment (scFv) directed against the c-Met receptor, to target the entry of recombinant retroviruses to human hepatocarcinoma cells. Four single-chain antibody fragments directed against the c-Met receptor were generated and inserted into the viral envelope protein as an N-terminal fusion. The modified envelopes were incorporated into virus particles and one of the chimeric viruses, 3D6-Env, transduced preferentially human hepatoma cells rather than proliferating human hepatocytes. In another construct, the urokinase cleavage site was inserted between the scFv moiety and the envelope. Chimeric scFv-urokinase-Env viruses transduced hepatoma cells with a similar efficiency to that of the control virus and their infectivity in human hepatocytes remained low. These results indicate that amphotropic retroviruses with engineered envelopes to display scFv directed against the c-Met receptor can efficiently and selectively deliver genes into hepatoma cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Región Variable de Inmunoglobulina
/
Técnicas de Transferencia de Gen
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Carcinoma Hepatocelular
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Proteínas Proto-Oncogénicas c-met
/
Neoplasias Hepáticas
Límite:
Humans
Idioma:
En
Revista:
Cancer Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
NEOPLASIAS
/
TERAPEUTICA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Francia