CHALLENGES IN GENE THERAPY RESEARCH FOR COAGULATION DISORDERS IN CONTEMPORARY SETTINGS
Keywords:
gene therapy challenges, hemophilia research, AAV immunogenicity, manufacturing constraints, healthcare disparities, clinical translationAbstract
The advent of gene therapy for inherited coagulation disorders represents a paradigm shift in hematology, yet the translation from promising preclinical models to widespread clinical implementation faces substantial obstacles. Despite regulatory approvals of adeno-associated virus (AAV)-based therapies for hemophilia A and B, numerous unresolved challenges constrain research advancement and clinical accessibility. This article examines contemporary problems in gene therapy research for bleeding disorders, analyzing immunological barriers, manufacturing limitations, durability uncertainties, economic constraints, and disparities in global access. Pre-existing anti-AAV neutralizing antibodies exclude 20-60% of potential candidates, vector production capacity remains insufficient for global demand, costs of $2-3 million per patient create prohibitive barriers, and long-term durability beyond 10-15 years remains unproven. Additionally, research infrastructure deficiencies in resource-limited settings, regulatory complexities, ethical considerations regarding patient selection, and technological limitations of current vector systems compound these challenges. Understanding and addressing these multifaceted problems is essential for advancing gene therapy research toward achieving equitable, durable, and cost-effective treatments for the global bleeding disorder population.
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