Highly Versatile Cell-Penetrating Peptide Loaded Scaffold For Efficient and Localized Gene Delivery To Multiple Cell Types From Development to Application in Tissue Engineering.pdf (2.01 MB)
Download fileHighly versatile cell-penetrating peptide loaded scaffold for efficient and localised gene delivery to multiple cell types: from development to application in tissue engineering
journal contribution
posted on 2022-08-04, 16:30 authored by Rosanne M. Raftery, David Walsh, Lia Blokpoel Ferreras, Irene Mencía Castaño, Gang Chen, Mark Lemoine, Gizem Osman, Kevin
M. Shakesheff, James E. Dixon, Fergal O'BrienFergal O'BrienGene 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 2 μg 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.
Funding
Science Foundation Ireland (SFI), Ireland, through the Advanced Materials and Bioengineering Research (AMBER) Centre (SFI/12/RC/2278)
Biotechnology and Biological Sciences Research Council: UK Regenerative Medicine Platform Hub “Acellular Approaches for Therapeutic Delivery” (MR/K026682/1)
Medical Research Council [grant number MR/K026682/1]
Engineering and Physical Sciences Research Council
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The original article is available at https://www.sciencedirect.com/Published Citation
Raftery RM, et al. 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. 2019;216:119277.Publication Date
13 June 2019PubMed ID
31252371Department/Unit
- Anatomy and Regenerative Medicine
- Tissue Engineering Research Group (TERG)
- Amber (Advanced Material & Bioengineering Research) Centre
- School of Pharmacy and Biomolecular Sciences
- Physiology and Medical Physics
Research Area
- Immunity, Infection and Inflammation
- Chemistry and Pharmaceutical Sciences
- Biomaterials and Regenerative Medicine
Publisher
Elsevier BVVersion
- Accepted Version (Postprint)
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Keywords
Cells, CulturedAnimalsRats, Sprague-DawleyRats, WistarCollagenVascular Endothelial Growth Factor ADNATissue EngineeringGene Transfer TechniquesOsteogenesisNeovascularization, PhysiologicMaleTissue ScaffoldsBone Morphogenetic Protein 2Cell-Penetrating PeptidesGenetic TherapyBone regenerationCell-penetrating peptideGETGene deliveryTissue engineeringBiomedical EngineeringRegenerative Medicine (incl. Stem Cells and Tissue Engineering)