Sj. Watkins et al., THE ADENOBODY APPROACH TO VIRAL TARGETING - SPECIFIC AND ENHANCED ADENOVIRAL GENE DELIVERY, Gene therapy, 4(10), 1997, pp. 1004-1012
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.