Viral and non-viral vectors for gene therapy in the treatment of bone-related disorders: molecular insights and clinical perspectives

Gene therapy offers a transformative approach for treating debilitating bone disorders by delivering therapeutic genetic material to target sites. The efficacy and safety of this approach are heavily reliant on the chosen delivery vehicle, either viral or non-viral vectors. Viral vectors are characterized by high transduction efficiency and the potential for long-term expression, as exemplified by Adeno-Associated Viruses (AAVs) and lentiviruses. However, their use is tempered by concerns over immunogenicity, manufacturing complexity, and safety. In contrast, non-viral vectors, which employ synthetic or physical methods, offer compelling advantages in safety, reduced immunogenicity, and manufacturing scalability but traditionally suffer from lower delivery efficiency. Ongoing research focuses on enhancing their cellular uptake and stability through advanced strategies such as lipid and polymer complexation and physical methods, aiming for targeted delivery to bone tissue. This includes the development of various nanocarriers and hydrogels designed to overcome physiological barriers. This study aims to comprehensively review and compare the current landscape of viral and non-viral gene therapy vectors, highlighting their mechanisms, advantages, disadvantages, and clinical applicability in the context of bone tissue regeneration and the treatment of bone disorders, with a focus on recent advancements and future directions to enhance therapeutic efficacy and safety.