Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation.

Autor:	Wilkinson P; Division of Oral Biology, School of Dentistry, University of Leeds, Leeds, United Kingdom.; CDT Tissue Engineering and Regenerative Medicine, Institute of Medical and Biological Engineering, University of Leeds, Leeds, United Kingdom., Bozo IY; Federal Medical Biophysical Center, Federal Medical-Biological Agency of Russia, Moscow, Russia., Braxton T; Division of Oral Biology, School of Dentistry, University of Leeds, Leeds, United Kingdom.; CDT Tissue Engineering and Regenerative Medicine, Institute of Medical and Biological Engineering, University of Leeds, Leeds, United Kingdom., Just P; Into Numbers Data Science GmbH, Vienna, Austria., Jones E; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom., Deev RV; Ryazan State Medical University, Ryazan, Russia., Giannoudis PV; Academic Department of Trauma and Orthopaedics, School of Medicine, University of Leeds, Leeds General Infirmary, Leeds, United Kingdom.; NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, United Kingdom., Feichtinger GA; Division of Oral Biology, School of Dentistry, University of Leeds, Leeds, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2021 Mar 17; Vol. 9, pp. 626315. Date of Electronic Publication: 2021 Mar 17 (Print Publication: 2021).
DOI:	10.3389/fbioe.2021.626315
Abstrakt:	Bone defects and improper healing of fractures are an increasing public health burden, and there is an unmet clinical need in their successful repair. Gene therapy has been proposed as a possible approach to improve or augment bone healing with the potential to provide true functional regeneration. While large numbers of studies have been performed in vitro or in vivo in small animal models that support the use of gene therapy for bone repair, these systems do not recapitulate several key features of a critical or complex fracture environment. Larger animal models are therefore a key step on the path to clinical translation of the technology. Herein, the current state of orthopedic gene therapy research in preclinical large animal models was investigated based on performed large animal studies. A summary and an outlook regarding current clinical studies in this sector are provided. It was found that the results found in the current research literature were generally positive but highly methodologically inconsistent, rendering a comparison difficult. Additionally, factors vital for translation have not been thoroughly addressed in these model systems, and the risk of bias was high in all reviewed publications. These limitations directly impact clinical translation of gene therapeutic approaches due to lack of comparability, inability to demonstrate non-inferiority or equivalence compared with current clinical standards, and lack of safety data. This review therefore aims to provide a current overview of ongoing preclinical and clinical work, potential bottlenecks in preclinical studies and for translation, and recommendations to overcome these to enable future deployment of this promising technology to the clinical setting. Competing Interests: IB is the CEO of the company Histograft, LLC. PJ is the CEO of the company Into Numbers Data Science GmbH. GF works as pro bono, non-salaried consultant for Histograft, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Wilkinson, Bozo, Braxton, Just, Jones, Deev, Giannoudis and Feichtinger.)
Databáze:	MEDLINE
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