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.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Nguyen TH,Loux N,Dagher I,Vons C,Carey K,Briand P,Hadchouel M,Franco D,Jouanneau J,Schwall R,Weber Adoi
10.1038/sj.cgt.7700640subject
Has Abstractpub_date
2003-11-01 00:00:00pages
840-9issue
11eissn
0929-1903issn
1476-5500pii
7700640journal_volume
10pub_type
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journal_title:Cancer gene therapy
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