{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:48:13Z","timestamp":1773236893406,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,1,24]],"date-time":"2008-01-24T00:00:00Z","timestamp":1201132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Transductional targeting of adenovirus following systemic or regional delivery remains one of the most difficult challenges for cancer gene medicine. The numerical excess and anatomical advantage of normal (non\u2010cancer) cells <jats:italic>in vivo<\/jats:italic> demand far greater detargeting than is necessary for studies using single cell populations <jats:italic>in vitro<\/jats:italic>, and this must be coupled with efficient retargeting to cancer cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adenovirus (Ad5) particles were coated with reactive poly[<jats:italic>N<\/jats:italic>\u2010(2\u2010hydroxypropyl)methacrylamide] copolymers, to achieve detargeting, and retargeting ligands were attached to the coating. Receptor\u2010mediated infection was characterised <jats:italic>in vitro<\/jats:italic> and anticancer efficacy was studied <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Polymer coating prevented the virus binding any cellular receptors and mediated complete detargeting <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. These fully detargeted vectors were efficiently retargeted with the model ligand FGF2 to infect FGFR\u2010positive cells. Specific transduction activity was the same as parental virus, and intracellular routing appeared unaffected. Levels of transduction were up to 100\u2010fold greater than parental virus on CAR negative cells. This level of specificity permitted good efficacy in intraperitoneal cancer virotherapy, simultaneously decreasing peritoneal adhesions seen with parental virus. Following intravenous delivery FGF2 mediated unexpected binding to erythrocytes, improving circulation kinetics, but preventing the targeted virus from leaving the blood stream.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Polymer cloaking enables complete adenovirus detargeting, providing a versatile platform for receptor\u2010specific retargeting. This approach can efficiently retarget cancer virotherapy <jats:italic>in vivo<\/jats:italic>. Ligands should be selected carefully, as non\u2010specific interactions with non\u2010target cells (e.g. blood cells) can deplete the pool of therapeutic virus available for targeting disseminated disease. 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