Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New retroviral constructs with a grafted specificity of infection could become useful gene delivery vehicles with applications in systemic gene therapy. We have constructed retroviral vectors to target gene transfer to human tumor cells. Chimeric envelope proteins have been expressed to obtain viral particles with a defined specificity of infection. Two tumor cell-specific recognition domains were cloned and fused with the viral envelope gene. A recognition domain specific for ErbB-2 expressing tumor cells was derived from a monoclonal antibody directed against the ErbB-2 receptor in the form of a single chain antibody domain (scFv-erbB-2). The receptor binding domain was derived from the heregulin gene (HRG70). This domain provides recognition specificity for ErbB-3 and ErbB-4 receptor expressing tumor cells. The recognition domains were inserted at the amino terminal end into the MoMLV envelope gene. Helper cell lines were established which express the recombinant envelope protein genes, the gag and pol genes and packageable retroviral RNA. The analysis of the helper cell line revealed that the recombinant ErbB-2 scFv-envelope protein was expressed, but not incorporated into viral particles. The scFv-erbB-2 envelope protein was not inserted into the cell membrane and the assembly of retroviral particles was not completed. In contrast, the HRG70-envelope protein was expressed on the surface of the helper cells and incorporated into retroviral particles. The HRG70-envelope protein, however, did not alter the host range of infection. Only cells expressing the ecotropic viral receptor could be infected.
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PMID:Expression of chimeric envelope proteins in helper cell lines and integration into Moloney murine leukemia virus particles. 873 65

Targeting retroviral entry is a central theme in the development of vectors for gene therapy. The host range of a retrovirus is dependent upon the interaction of its envelope glycoprotein (Env) with a specific cell surface receptor protein, which allows viral entry. In contrast, the pH-dependent viruses enter cells through receptor-mediated endocytosis and the subsequent acidification produces conformational changes in the viral envelope protein(s) which lead to membrane fusion. We attempted to redirect retroviral vectors to epidermal growth factor (EGF) receptor expressing cells by using the pH-dependent influenza A virus hemagglutinin (HA). Wild type receptor binding was avoided either by point mutations or by deletion of the globular head structure of HA and also inserted EGF into HA. Replacement of the whole head domain was not tolerated. Two of the EGF-HA proteins bearing point mutations could be incorporated into retroviral particles, but unfortunately their fusion activity was lost. The data indicate that care must be taken when mutating multiple sites in HA, and that targeting HA requires further analysis of appropriate sites for the insertion of foreign sequences.
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PMID:Retroviral vector targeting through insertion of epidermal growth factor into receptor binding deficient influenza A hemagglutinin results in fusion defective particles. 1528 62