A ligand-pseudoreceptor system based on de novo designed peptides for the generation of adenoviral vectors with altered tropism

The Journal of Gene Medicine
Yue ZengBernard Massie

Abstract

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. 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). 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 to...Continue Reading

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Citations

Aug 30, 2008·Journal of Virology·Hongjie WangAndré Lieber
Oct 13, 2011·Cancer Research·Ines BeyerAndré Lieber
Feb 6, 2010·Expert Opinion on Biological Therapy·Karoly TothWilliam S M Wold
Dec 9, 2008·Protein Expression and Purification·Phuong U LeMaureen D O'Connor-McCourt
Oct 31, 2013·Journal of the American Association of Nurse Practitioners·Galadriel Bonnel
May 28, 2020·Cold Spring Harbor Protocols·Miguel Sena-Esteves, Guangping Gao
Jul 19, 2016·Expert Review of Proteomics·Rebecca Christine Feiner, Kristian Mark Müller

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