US20250381295
2025-12-18
Human necessities
A61K48/005
The patent application introduces lentiviral vectors designed for gene therapy targeting alpha thalassemia, a genetic disorder characterized by reduced or absent synthesis of alpha-globin chains in hemoglobin. The vectors incorporate an alpha-globin gene within an expression cassette to restore balanced globin chain production. This approach aims to address the severe forms of the disease, which result in anemia and other complications due to imbalanced globin synthesis.
Alpha thalassemia (AT) is a prevalent genetic condition that affects the production of hemoglobin's alpha-globin chains, leading to a range of health issues, including anemia. The severity of AT varies based on the number of non-functional alpha-globin genes, with the most severe form, alpha thalassemia major, historically being lethal in utero. The disease is notably common in regions such as Asia and the Middle East and is increasingly recognized in Western countries due to migration patterns.
Current treatments for severe AT involve lifelong blood transfusions and iron chelation therapy, which pose significant burdens on patients and healthcare systems. Allogeneic hematopoietic stem cell transplantation offers a potential cure but is limited by donor availability and associated risks. Autologous transplantation of gene-modified hematopoietic stem cells presents a promising alternative, yet current gene therapy trials have primarily focused on beta thalassemia, leaving a gap in treatment options for AT.
The proposed lentiviral vectors include a recombinant expression cassette with an alpha-globin gene, flanked by regulatory sequences from globin genes, and a locus control region (LCR) to enhance expression. Various embodiments detail the use of different LCRs and configurations of the alpha-globin gene, including full-length genes, cDNA, and codon-optimized sequences. These vectors are designed to integrate into patient-derived hematopoietic stem cells, potentially offering a curative therapy for AT.
This gene therapy approach could revolutionize the treatment of alpha thalassemia by providing a sustainable and effective alternative to current therapies. By addressing the underlying genetic cause of the disorder, these vectors have the potential to restore normal hemoglobin production, reduce the need for transfusions, and improve the quality of life for patients. The development of these vectors represents a significant advancement in the field of gene therapy for inherited blood disorders.