Reconstituted influenza virus envelopes (virosomes) containing the viral he
magglutinin (HA) have attracted attention as delivery vesicles for cytosoli
c drug delivery as they possess membrane fusion activity. Here, we show tha
t influenza virosomes can be targeted towards ovarian carcinoma cells (OVCA
R-3) with preservation of fusion activity. This was achieved by incorporati
ng poly(ethylene glycol) (PEG)-derivatized lipids into the virosome membran
e. This PEG layer serves as shield to prevent interaction of HA with ubiqui
tous sialic acid residues and as spatial anchor for antibody attachment. Co
upling of Fab' fragments of mAb 323/A3 (anti-epithelial glycoprotein-2) to
the distal ends of PEG lipids resulted in specific binding of virosomes to
OVCAR-3 cells. These antibody-redirected virosomes fused with membranes of
OVCAR-3 cells in a pH-dependent fashion. (C) 2001 Published by Elsevier Sci
ence B.V. on behalf of the Federation of European Biochemical Societies.