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In vitro and in vivo properties of adenovirus vectors with increased affinity to CD46.

Wang, H, Liu, Y, Li, Z, Tuve, S, Stone, D, Kalyushniy, O, Shayakhmetov, D, Verlinde, CL, Stehle, T, McVey, J , Baker, A, Peng, KW, Roffler, S and Lieber, A (2008) In vitro and in vivo properties of adenovirus vectors with increased affinity to CD46. J Virol, 82 (21). pp. 10567-10579.

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Gene transfer vectors containing adenovirus (Ad) serotype 35 (Ad35) fibers have shown promise for cancer and stem cell gene therapy. In this study, we attempted to improve the in vitro and in vivo infection properties of these vectors by increasing their affinity to the Ad35 fiber receptor CD46. We constructed Ad vectors containing either the wild-type Ad35 fiber knob (Ad5/35) or Ad35 knob mutants with 4-fold- and 60-fold-higher affinity to CD46 (Ad5/35+ and Ad5/35++, respectively). In in vitro studies with cell lines, the higher affinities of Ad5/35+ and Ad5/35++ to CD46 did not translate into correspondingly higher transduction efficiencies, regardless of the CD46 receptor density present on cells. However, in vivo, in a mouse model with preestablished CD46(high) liver metastases, intravenous injection of Ad5/35++ resulted in more-efficient tumor cell transduction. We conclude that Ad5/35 vectors with increased affinity to CD46 have an advantage in competing with non-CD46-mediated sequestration of vector particles after intravenous injection.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Wang, H
Liu, Y
Li, Z
Tuve, S
Stone, D
Kalyushniy, O
Shayakhmetov, D
Verlinde, CL
Stehle, T
Baker, A
Peng, KW
Roffler, S
Lieber, A
Date : November 2008
DOI : 10.1128/JVI.01308-08
Uncontrolled Keywords : Adenoviridae, Animals, Antigens, CD46, Capsid Proteins, Cell Line, Cricetinae, Genetic Therapy, Genetic Vectors, Humans, Mice, Mice, Inbred C57BL, Mutation, Neoplasms, Receptors, Virus, Transduction, Genetic, Virus Attachment
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:56
Last Modified : 24 Jan 2020 18:06

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