Development of adenovirus immobilization strategies for in situ gene therapy
dc.contributor.author | Hu, Wei-Wen | en_US |
dc.contributor.author | Lang, Michael W. | en_US |
dc.contributor.author | Krebsbach, Paul H. | en_US |
dc.date.accessioned | 2008-10-01T15:22:35Z | |
dc.date.available | 2009-11-06T18:12:56Z | en_US |
dc.date.issued | 2008-10 | en_US |
dc.identifier.citation | Hu, Wei-Wen; Lang, Michael W.; Krebsbach, Paul H. (2008). "Development of adenovirus immobilization strategies for in situ gene therapy." The Journal of Gene Medicine 10(10): 1102-1112. <http://hdl.handle.net/2027.42/60964> | en_US |
dc.identifier.issn | 1099-498X | en_US |
dc.identifier.issn | 1521-2254 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/60964 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18618417&dopt=citation | en_US |
dc.description.abstract | Background Regenerative gene therapy using viral vectors enables transduced cells to express bioactive factors in vivo . Viral delivery with spatial control can enhance transduction efficiency and may limit systemic infection. Consequently, we tethered biotinylated adenovirus via interactions with avidin on chitosan surfaces to gain robust control for in situ transduction. Methods Avidin was either directly conjugated to chitosan (virus–biotin–avidin-material; VBAM) or indirectly docked on biotinylated chitosan surfaces (virus–biotin–avidin–biotin-material; VBABM) to tether biotinylated adenovirus. Enzyme-linked immunosorbent assay (ELISA) and spectroscopic analysis were performed to demonstrate the binding profiles. Biotin-alkaline phosphatase and biotinylated adenovirus were used as different sized particles to evaluate binding efficiencies and were compared by the Sips isotherm adsorption method. Scanning electron microscopy (SEM) examination illustrated virus distribution, and the transduction efficiency was determined by in vitro cell transduction. Results ELISA and spectroscopic analysis both demonstrated that the VBAM system led to multilayer avidin formation on biomaterial surfaces, whereas VBABM formed a monolayer of avidin. Sips isotherm adsorption indicated that the VBAM method increased heterogeneity and steric hindrance of binding sites. By contrast, the VBABM method docked avidin on chitosan surfaces and orientated the binding sites to facilitate ligand binding. In addition, SEM images illustrated that the VBABM method led to more even viral distribution. In vitro cell infection experiments also demonstrated that the VBABM system enhanced virus immobilization and thus improved cell transduction efficiency over the VBAM system. Conclusions The VBABM strategy is a superior method for in situ transduction from biomaterials. This strategy could be adapted for use with a variety of biomaterials as well as viral vectors, and thus may be an alternative method for in vivo regenerative gene therapy. Copyright © 2008 John Wiley & Sons, Ltd. | en_US |
dc.format.extent | 289470 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | John Wiley & Sons, Ltd. | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Genetics | en_US |
dc.title | Development of adenovirus immobilization strategies for in situ gene therapy | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA ; Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, USA | en_US |
dc.contributor.affiliationum | Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, USA | en_US |
dc.contributor.affiliationum | Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA ; Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, USA ; Department of Biologic and Materials Sciences, School of Dentistry, K1030, 1011 North University Avenue, University of Michigan, Ann Arbor, MI 48109-1078, USA. | en_US |
dc.identifier.pmid | 18618417 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/60964/1/1233_ftp.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/jgm.1233 | en_US |
dc.identifier.source | The Journal of Gene Medicine | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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