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Gene therapy for chondral and osteochondral regeneration: is the future now?
Daniele Bellavia1,2, F Veronesi3, V Carina4,5
1Rizzoli Orthopedic Institute, Bologna, Italy. daniele.bellavia@ior.it.
Abstract:
Gene therapy might represent a promising strategy for chondral and osteochondral defects repair by balancing the management of temporary joint mechanical incompetence with altered metabolic and inflammatory homeostasis. This review analysed preclinical and clinical studies on gene therapy for the repair of articular cartilage defects performed over the last 10 years, focussing on expression vectors (non-viral and viral), type of genes delivered and gene therapy procedures (direct or indirect). Plasmids (non-viral expression vectors) and adenovirus (viral vectors) were the most employed vectors in preclinical studies. Genes delivered encoded mainly for growth factors, followed by transcription factors, anti-inflammatory cytokines and, less frequently, by cell signalling proteins, matrix proteins and receptors. Direct injection of the expression vector was used less than indirect injection of cells, with or without scaffolds, transduced with genes of interest and then implanted into the lesion site. Clinical trials (phases I, II or III) on safety, biological activity, efficacy, toxicity or bio-distribution employed adenovirus viral vectors to deliver growth factors or anti-inflammatory cytokines, for the treatment of osteoarthritis or degenerative arthritis, and tumour necrosis factor receptor or interferon for the treatment of inflammatory arthritis.
Insights
Gene therapy shows promise for cartilage repair, utilizing various vectors and gene types. Clinical trials focus on osteoarthritis and inflammatory arthritis treatments.
Area of Science:
- Orthopedics and Regenerative Medicine
- Biotechnology and Gene Therapy
Background:
- Articular cartilage defects pose significant challenges in joint repair.
- Gene therapy offers a potential strategy to restore joint homeostasis and mechanical function.
Purpose of the Study:
- To review preclinical and clinical studies on gene therapy for articular cartilage defect repair over the past decade.
- To analyze expression vectors, gene types, and delivery methods used in gene therapy for cartilage repair.
Main Methods:
- Analysis of preclinical and clinical studies focusing on gene therapy for articular cartilage defects.
- Categorization of studies based on expression vectors (viral and non-viral), delivered genes, and administration procedures (direct vs. indirect).
Main Results:
- Plasmids and adenoviruses were common vectors in preclinical research.
- Growth factors were the most frequently delivered genes, followed by transcription factors and anti-inflammatory cytokines.
- Indirect gene delivery via transduced cells and scaffolds was more common than direct vector injection.
Conclusions:
- Gene therapy, particularly using viral vectors like adenovirus, is being explored in clinical trials for osteoarthritis and inflammatory arthritis.
- Delivery of growth factors and anti-inflammatory agents via gene therapy holds potential for treating joint degenerative and inflammatory conditions.
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