Viral and non-viral vectors in gene therapy: current state and clinical perspectives.

Abstract

Advancements in gene therapy have achieved significant milestones in treating human diseases, offering renewed hope to patients with limited options. Key to this progress are vectors, which include both viral and non-viral methodologies that impact the success of gene therapy. Over the past two decades, three widely used viral vectors-lentiviruses (LV), adenoviruses (Ad), and adeno-associated viruses (AAV)-have enabled notable preclinical and clinical successes, including the approval of Luxturna for a genetic retinal disease and CAR-T therapies for blood cancers. Recently, the first-in-human dual AAV therapy for hereditary hearing loss, which overcomes large gene delivery, has showcased the restoration of auditory function for patients. Additionally, non-viral vectors such as lipid nanoparticles (LNP) and N-acetylgalactosamine (GalNAc) have led to successful gene therapy products. This review focuses on both viral and non-viral delivery systems in gene therapy, highlighting their current state and future perspectives in treating human diseases.