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Efficient incorporation of a functional hyper-stable single-chain antibody fragment protein-IX fusion in the adenovirus capsid.

Abstract : Recombinant adenoviruses are frequently used as gene transfer vehicles for therapeutic gene delivery. Strategies to amend their tropism include the incorporation of polypeptides with high affinity for cellular receptors. Single-chain antibodies have a great potential to achieve such cell type specificity. In this study, we evaluated the efficiency of incorporation of a single-chain antibody fused with the adenovirus minor capsid protein IX in the capsid of adenovirus type 5 vectors. To this end, the codons for the single-chain antibody fragments (scFv) 13R4 were fused with those encoding of pIX via a 75-Angstrom spacer sequence. The 13R4 is a hyper-stable single-chain antibody directed against beta-galactosidase, which was selected for its capacity to fold correctly in a reducing environment such as the cytoplasm. A lentiviral vector was used to stably express the pIX.flag.75.13R4.MYC.HIS fusion gene in 911 helper cells. Upon propagation of pIX-gene deleted human adenovirus-5 vectors on these cells, the pIX-fusion protein was efficiently incorporated in the capsid. Here, the 13R4 scFv was functional as was evident from its capacity to bind its ligand beta-galactosidase. These data demonstrate that the minor capsid protein IX can be used as an anchor for incorporation of single-chain antibodies in the capsids of adenovirus vectors.
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https://www.hal.inserm.fr/inserm-00147343
Contributor : Yves Le Ster <>
Submitted on : Monday, October 15, 2007 - 3:21:41 PM
Last modification on : Monday, May 27, 2019 - 1:16:02 PM
Document(s) archivé(s) le : Wednesday, April 7, 2010 - 3:38:26 AM

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Jort Vellinga, Jeroen de Vrij, Susanna Myhre, Taco Uil, Pierre Martineau, et al.. Efficient incorporation of a functional hyper-stable single-chain antibody fragment protein-IX fusion in the adenovirus capsid.. Gene Therapy, Nature Publishing Group, 2007, 14 (8), pp.664-70. ⟨10.1038/sj.gt.3302908⟩. ⟨inserm-00147343⟩

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