THE ADENOBODY APPROACH TO VIRAL TARGETING - SPECIFIC AND ENHANCED ADENOVIRAL GENE DELIVERY

Citation
Sj. Watkins et al., THE ADENOBODY APPROACH TO VIRAL TARGETING - SPECIFIC AND ENHANCED ADENOVIRAL GENE DELIVERY, Gene therapy, 4(10), 1997, pp. 1004-1012
Citations number
39
Categorie Soggetti
Pharmacology & Pharmacy","Genetics & Heredity",Biology
Journal title
ISSN journal
09697128
Volume
4
Issue
10
Year of publication
1997
Pages
1004 - 1012
Database
ISI
SICI code
0969-7128(1997)4:10<1004:TAATVT>2.0.ZU;2-V
Abstract
Recombinant adenoviruses have enormous potential as vectors for gene t herapy. They have evolved an efficient method of infection and a wide host range but this leads to concerns about the specificity of gene de livery. In order to target an adenovirus type 5-based vector we have i nvestigated an antibody approach. A virus neutralising scFv antibody f ragment was isolated from a phage library and a C-terminal fusion prot ein with epidermal growth factor (EGF) constructed. This fusion protei n, or 'adenobody', bound both to the fibre protein of the adenovirus a nd to the EGF receptor (EGFR) on human cells, and was able to direct a denoviral binding to the new receptor. Using this system the efficienc y of viral infection was markedly enhanced and was targeted to the EGF R. The adenobody-directed infection correlated with the level of EGF r eceptor expressed on the cells and could be blocked by competition wit h pure EGF. Peptide inhibition experiments suggest that infection is m ediated directly through attachment to the EGFR and does not require p enton-integrin interactions. This work shows that the 'adenobody' appr oach can enhance the efficiency as well as target adenoviral infection and has numerous potential applications for gene therapy.