Rosanne M. Raftery
Highly versatile cell-penetrating peptide loaded scaffold for efficient and localised gene delivery to multiple cell types: From development to application in tissue engineering
Raftery, Rosanne M.; Walsh, David P.; Blokpoel Ferreras, Lia; Mencía Castaño, Irene; Chen, Gang; LeMoine, Mark; Osman, Gizem; Shakesheff, Kevin M.; Dixon, James E.; O'Brien, Fergal J.
David P. Walsh
Lia Blokpoel Ferreras
Irene Mencía Castaño
Prof KEVIN SHAKESHEFF KEVIN.SHAKESHEFF@NOTTINGHAM.AC.UK
Pro-Vice Chancellor - Faculty of Science
James E. Dixon
Fergal J. O'Brien
Gene therapy has recently come of age with seven viral vector-based therapies gaining regulatory approval in recent years. In tissue engineering, non-viral vectors are preferred over viral vectors, however, lower transfection efficiencies and difficulties with delivery remain major limitations hampering clinical translation. This study describes the development of a novel multi-domain cell-penetrating peptide, GET, designed to enhance cell interaction and intracellular translocation of nucleic acids; combined with a series of porous collagen-based scaffolds with proven regenerative potential for different indications. GET was capable of transfecting cell types from all three germ layers, including stem cells, with an efficiency comparable to Lipofectamine® 3000, without inducing cytotoxicity. When implanted in vivo, GET gene-activated scaffolds allowed for host cell infiltration, transfection localized to the implantation site and sustained, but transient, changes in gene expression – demonstrating both the efficacy and safety of the approach. Finally, GET carrying osteogenic (pBMP-2) and angiogenic (pVEGF) genes were incorporated into collagen-hydroxyapatite scaffolds and with a single 2μg dose of therapeutic pDNA, induced complete repair of critical-sized bone defects within 4 weeks. GET represents an exciting development in gene therapy and by combining it with a scaffold-based delivery system offers tissue engineering solutions for a myriad of regenerative indications.
|Journal Article Type||Article|
|Peer Reviewed||Peer Reviewed|
|APA6 Citation||Raftery, R. M., Walsh, D. P., Blokpoel Ferreras, L., Mencía Castaño, I., Chen, G., LeMoine, M., …O'Brien, F. J. (2019). Highly versatile cell-penetrating peptide loaded scaffold for efficient and localised gene delivery to multiple cell types: From development to application in tissue engineering. Biomaterials, 216, doi:10.1016/j.biomaterials.2019.119277|
|Keywords||GET; Gene delivery; Cell-penetrating peptide; Tissue engineering; Bone regeneration|
|Additional Information||This article is maintained by: Elsevier; Article Title: Highly versatile cell-penetrating peptide loaded scaffold for efficient and localised gene delivery to multiple cell types: From development to application in tissue engineering; Journal Title: Biomaterials; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016...omaterials.2019.119277; Content Type: article; Copyright: © 2019 Elsevier Ltd. All rights reserved.|
This file is under embargo until Jun 13, 2020 due to copyright restrictions.
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