Advances in gene transfer technologies: comparing viral and non-viral vectors for therapeutic applications

Abstract Gene and cell therapies have emerged as transformative approaches for treating a wide range of genetic and acquired diseases. Central to their success is the development of safe and effective gene delivery systems, categorized broadly into viral and non-viral vectors. Each system has its own advantages and limitations, requiring careful consideration of the target tissue, disease, and the balance between safety, efficacy, and scalability. Viral vectors, including adeno-associated viruses, retroviruses, lentiviruses, herpes simplex viruses, and adenoviruses, offer high transduction efficiency and specificity but raise concerns about immunogenicity and production challenges. Non-viral systems, such as lipid nanoparticles (LNPs) and other synthetic carriers, provide scalable, cost-effective, and potentially safer alternatives but often face hurdles in transduction efficiency and targeted delivery. This review provides a comprehensive overview of the current status of these vector systems for in vivo and ex vivo applications. Key comparisons are made across safety, efficacy, scalability, and immune responses, highlighting recent advancements and innovative approaches. We also discuss the outlook for next-generation gene transfer technologies, focusing on improvements in vector design, manufacturing, and application versatility. By addressing these considerations, we aim to inform the development of optimized therapeutic strategies that leverage the unique strengths of each delivery system.