[en] Osteoarthritis (OA) is a multifactorial joint disease characterized by progressive cartilage degradation, synovial inflammation, and subchondral bone remodeling. Despite its significant global health burden, there are currently no disease-modifying pharmacological therapies for OA. Gene therapy, leveraging viral and non-viral vectors to deliver therapeutic transgenes into the joint environment, shows significant promise. This mini-review highlights recent innovations in OA gene therapy pipelines, focusing on Platforms employing recombinant adenovirus, adeno-associated virus (AAV), and herpes simplex virus vectors. Strategies include AAV-mediated delivery of interleukin-1 receptor antagonist (IL-1Ra) and truncated nkx3.2 transcription factor to modulate inflammation and promote chondrocyte survival. Non-viral approaches, such as plasmid DNA encoding interleukin-10, are also under investigation. Emerging data from preclinical and clinical studies demonstrate the feasibility of achieving sustained, intra-articular transgene expression with therapeutic efficacy in animal models and early-phase human trials. However, challenges persist, including immune barriers to repeat dosing, variability in vector performance, and the high costs of treatment. Additionally, agerelated declines in transduction efficiency, the heterogeneity of OA, and systemic metabolic influences complicate therapeutic outcomes. To overcome current regulatory obstacles, future research must prioritize the refinement of vector systems to enhance safety, potency, and specificity, as well as the development of combination therapies integrating genetic and conventional approaches, targeting pain and improving function. Gene therapy has transformative potential for improving OA management and an important priority is multidisciplinary collaboration to translate preclinical innovations into accessible, effective treatments for a highly heterogeneous and aging patient population.
Disciplines :
Public health, health care sciences & services
Author, co-author :
Peitso, Valtteri ; Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
Ng, Karman ; KNG Consulting LLC, Livingston, NJ, USA
Ellis, Ron; KNG Consulting LLC, Livingston, NJ, USA
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique ; Protein Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
Evans, Christopher H ; Departments of Physical Medicine & Rehabilitation, Orthopedic Surgery and Molecular Medicine, Mayo Clinic, Rochester, NY, USA
Mobasheri, Ali ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé ; Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland ; Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania ; Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Language :
English
Title :
Gene therapy pipelines for osteoarthritis: current innovations, operational challenges, and future directions.
COST - European Cooperation in Science and Technology EU - European Union Research Council of Finland
Funding text :
European Cooperation in Science and Technology [CA21110]. HORIZON EUROPE Framework Programme [101095635]. Research Council of Finland [336449, 351568]. AM and VP wish to acknowledge the generous financial support of Suomen Akatemia/Research Council of Finland Profi6 grant number 336449 and grant number 351568 awarded to the University of Oulu. AM also acknowledges funding from Horizon Europe (PROTO-Advanced PeRsOnalized Therapies for Osteoarthritis-TACKLING INFLAMMATION TO IMPROVE PATIENT OUTCOMES, Grant agreement ID: 101095635, https://cordis.europa.eu/project/id/101095635. and ENgineered CArtilage from Nose for the Treatment of Osteoarthritis [ENCANTO], Grant agreement ID: 101137315, https://cordis.europa.eu/project/id/101137315). We also acknowledge the support from the European Cooperation in Science and Technology COST Association Action CA21110\u2013Building an open European Network on Osteoarthritis Research (NetwOArk); https://www.cost.eu/actions/CA21110/). VP acknowledges support from Orion Research Foundation sr. CHE\u2019s research is funded, in part, by the John and Posy Krehbiel Professorship in Orthopedics. The contribution of JYR to the manuscript has been funded by the Distinguished Scientist Fellowship Program (DSFP) of the King Saud University, Riyadh, Kingdom of Saudi Arabia.AM and VP wish to acknowledge the generous financial support of Suomen Akatemia/Research Council of Finland Profi6 grant number 336449 and grant number 351568 awarded to the University of Oulu. AM also acknowledges funding from Horizon Europe (PROTO-Advanced PeRsOnalized Therapies for Osteoarthritis-TACKLING INFLAMMATION TO IMPROVE PATIENT OUTCOMES, Grant agreement ID: 101095635, https://cordis.europa.eu/project/id/101095635 . and ENgineered CArtilage from Nose for the Treatment of Osteoarthritis [ENCANTO], Grant agreement ID: 101137315, https://cordis.europa.eu/project/id/101137315 ). We also acknowledge the support from the European Cooperation in Science and Technology COST Association Action CA21110\u2013Building an open European Network on Osteoarthritis Research (NetwOArk); https://www.cost.eu/actions/CA21110/ ). VP acknowledges support from Orion Research Foundation sr. CHE\u2019s research is funded, in part, by the John and Posy Krehbiel Professorship in Orthopedics. The contribution of JYR to the manuscript has been funded by the Distinguished Scientist Fellowship Program (DSFP) of the King Saud University, Riyadh, Kingdom of Saudi Arabia.
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