Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation
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....
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| Format: | Article |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2021.626315/full |
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| author | Piers Wilkinson Piers Wilkinson Ilya Y. Bozo Thomas Braxton Thomas Braxton Peter Just Elena Jones Roman V. Deev Peter V. Giannoudis Peter V. Giannoudis Georg A. Feichtinger |
| author_facet | Piers Wilkinson Piers Wilkinson Ilya Y. Bozo Thomas Braxton Thomas Braxton Peter Just Elena Jones Roman V. Deev Peter V. Giannoudis Peter V. Giannoudis Georg A. Feichtinger |
| author_sort | Piers Wilkinson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T06:24:01Z |
| format | Article |
| id | doaj.art-0f6c1889b40a413ba8a5e05bc1502bd9 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-16T06:24:01Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-0f6c1889b40a413ba8a5e05bc1502bd92022-12-21T22:41:03ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-03-01910.3389/fbioe.2021.626315626315Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical TranslationPiers Wilkinson0Piers Wilkinson1Ilya Y. Bozo2Thomas Braxton3Thomas Braxton4Peter Just5Elena Jones6Roman V. Deev7Peter V. Giannoudis8Peter V. Giannoudis9Georg A. Feichtinger10Division of Oral Biology, School of Dentistry, University of Leeds, Leeds, United KingdomCDT Tissue Engineering and Regenerative Medicine, Institute of Medical and Biological Engineering, University of Leeds, Leeds, United KingdomFederal Medical Biophysical Center, Federal Medical-Biological Agency of Russia, Moscow, RussiaDivision of Oral Biology, School of Dentistry, University of Leeds, Leeds, United KingdomCDT Tissue Engineering and Regenerative Medicine, Institute of Medical and Biological Engineering, University of Leeds, Leeds, United KingdomInto Numbers Data Science GmbH, Vienna, AustriaLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United KingdomRyazan State Medical University, Ryazan, RussiaAcademic Department of Trauma and Orthopaedics, School of Medicine, University of Leeds, Leeds General Infirmary, Leeds, United KingdomNIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, United KingdomDivision of Oral Biology, School of Dentistry, University of Leeds, Leeds, United KingdomBone 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.https://www.frontiersin.org/articles/10.3389/fbioe.2021.626315/fullbone regenerationgene therapypreclinical modelstranslational medical researchorthopedic and traumaregenerative medicine |
| spellingShingle | Piers Wilkinson Piers Wilkinson Ilya Y. Bozo Thomas Braxton Thomas Braxton Peter Just Elena Jones Roman V. Deev Peter V. Giannoudis Peter V. Giannoudis Georg A. Feichtinger Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation Frontiers in Bioengineering and Biotechnology bone regeneration gene therapy preclinical models translational medical research orthopedic and trauma regenerative medicine |
| title | Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation |
| title_full | Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation |
| title_fullStr | Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation |
| title_full_unstemmed | Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation |
| title_short | Systematic Review of the Preclinical Technology Readiness of Orthopedic Gene Therapy and Outlook for Clinical Translation |
| title_sort | systematic review of the preclinical technology readiness of orthopedic gene therapy and outlook for clinical translation |
| topic | bone regeneration gene therapy preclinical models translational medical research orthopedic and trauma regenerative medicine |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2021.626315/full |
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