| DOI | Resolve DOI: https://doi.org/10.1002/jgm.1155 |
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| Author | Search for: Zeng, Yue1; Search for: Pinard, Maxime1; Search for: Jaime, Jaïro1; Search for: Bourget, Lucie1; Search for: Le, Phuong Uyen1; Search for: O'Connor-McCourt, Maureen D.1; Search for: Gilbert, Rénald1; Search for: Massie, Bernard1 |
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| Affiliation | - National Research Council of Canada. NRC Biotechnology Research Institute
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| Format | Text, Article |
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| Subject | biotechnology; Cell Line; Cells; Epidermal Growth Factor; Ligands; methods; Peptides; pharmaceutical; Transgenes; adenovirus; retargeting; packaging cells; pseudoreceptor; gene therapy; fiber |
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| Abstract | Background: Delivery of transgenes into specific tissues by adenovirus vectors (AdVs) relies on ablations of their natural tropism and on introduction of a new tropism. If the interaction with its natural receptor is ablated, a new packaging cell line is required to produce the AdV. In the present study, we have used two de novo designed peptides (E-Coil and K-Coil) that interact with each other with high affinity to establish a new receptor-ligand system for the propagation of retargeted AdVs. Methods: We produced a cell line (293E) expressing on its surface a pseudoreceptor containing the E-Coil. An AdV (AdFK4m/GFP) lacking the interaction with the primary receptor for adenovirus (CAR) and containing the K-Coil inserted at the fiber C-terminus was constructed and tested using two strategies: (1) an RGD motif (Arg-Gly-Asp) was inserted into the HI-loop of the fiber; (2) AdFK4m/GFP was conjugated to a bispecific adaptor for the epidermal growth factor receptor (EGFR). Results: AdFK4m/GFP infected 293E cells more efficiently than cells lacking the pseudoreceptor. The transduction was due to the K-Coil/E-Coil specific interaction since it was competed by addition of soluble K-Coil, but not soluble fiber. We demonstrated that the modified AdV was retargeted toward αv integrin by inclusion of the RGD motif, or toward EGFR using the bispecific adaptor. Conclusions: We have established a new system to produce AdVs ablated of natural tropism. This system should permit the retargeting of AdVs by inserting new ligandswithin the fiber or through the interactionwith bispecific adaptors. |
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| Publication date | 2008-01-14 |
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| In | |
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| Language | English |
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| NRC number | NRCC 47814 |
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| NPARC number | 3539700 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | b730416e-458b-48d9-b300-ecf4ae06776a |
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| Record created | 2009-03-01 |
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| Record modified | 2020-04-15 |
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