Non-Viral Gene Therapy Systems for Orthopaedics

Ex vivo or in situ genetic manipulation of suitable target cells offers effective avenues to achieve true functional regeneration of tissues in vivo through induced autoregeneration. The augmentation or down-regulation of endogenous effectors of cell behavior through delivery of nucleic acids offers a targeted and fine-tuned approach for biomimetic approaches to manipulate cellular behavior. Non-viral, transient genetic manipulation in regenerative medicine is a field particularly amenable to accelerated translation and deployment for patient benefit due to its safety and cost-effectiveness. Such approaches have been demonstrated to be feasible and useful in preclinical studies for musculoskeletal regeneration and could become viable alternatives or supportive therapies to current clinical standards if current limitations of efficacy and control of delivery can be improved.

Therefore, this Research Topic aims at providing a comprehensive and current overview of preclinical systems that are in development for application as non-viral gene therapies for musculoskeletal disorders, in particular novel approaches that can address delivery efficacy and spatiotemporal control. This includes ex vivo gene therapies that involve in vitro stem cell manipulation as well as approaches for direct in vivo genetic manipulation, limited to non-viral nucleic acid delivery aimed at addressing a clinical problem in the musculoskeletal field. Submissions covering systems to improve efficacy through novel agents or combinations with biomaterials are encouraged as are innovative strategies for advanced spatiotemporal control of delivery and new avenues to endogenous gene regulation/reprogramming.