Viral vector-based gene therapies in the clinic: An update

Gene therapy has advanced considerably in recent years, driven by innovations in vector engineering and a more advanced understanding of virology for clinical translation. Since 2021, the U.S. Food and Drug Administration (FDA) has approved seven new viral vector-based gene therapies, five of which use adeno-associated virus (AAV) vectors, reinforcing their status as the leading platform for in vivo gene delivery. These approvals encompassed hematologic, neuromuscular, dermatologic, and neurogenetic diseases, using diverse serotypes and delivery routes tailored to the therapeutic context. Disease-specific patterns of capsid usage reveal advancement in tailored capsid engineering based on anatomical targeting needs. Beyond AAV, non-AAV vectors, such as herpes simplex virus (HSV) and adenovirus, are actively explored in cancer trials, while lentiviral vectors support applications in oncology and immune-related disorders. This review provides an updated analysis of the clinical landscape of viral vector-based gene therapies, highlighting new FDA-approved products and ongoing clinical trials by vector type, disease indication, and clinical phase since our original review in 2021. Our analysis highlights advances in viral vector technologies that reflect a maturing field, transitioning from proof-of-concept studies to precision platforms increasingly capable of addressing rare monogenic disorders and more prevalent, complex diseases.