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)
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Highly versatile cell-penetrating peptide loaded scaffold for efficient and localised gene delivery to multiple cell types: from development to application in tissue engineering

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journal contribution
posted on 04.08.2022, 16:30 authored by Rosanne M. Raftery, David Walsh, Lia Blokpoel Ferreras, Irene Mencía Castaño, Gang ChenGang Chen, Mark Lemoine, Gizem Osman, Kevin M. Shakesheff, James E. Dixon, Fergal O'BrienFergal 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 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

History

Comments

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 2019

PubMed ID

31252371

Department/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 BV

Version

  • Accepted Version (Postprint)