RPS19-encoding lentiviral vector and method of using the same
A self-inactivating lentiviral vector encoding codon-optimized RPS19 addresses the limitations of current Diamond-Blackfan anemia treatments by safely transducing hematopoietic stem cells, alleviating DBAS phenotypes and providing a potential cure with reduced toxicity.
Patent Information
- Application Number
- PCT/US2025/052592
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-11-04
- Filing Date
- 2025-10-27
- Publication Date
- 2026-05-07
AI Technical Summary
Current treatments for Diamond-Blackfan anemia syndrome, such as corticosteroids and allogeneic hematopoietic stem cell transplantation, are associated with serious long-term toxicities and suboptimal quality of life, and safe and effective lentiviral vector-based gene therapies are needed to address the hematopoietic defects caused by ribosomal protein S19 mutations.
A self-inactivating lentiviral vector encoding codon-optimized RPS19 nucleic acids linked to an EFla or MND promoter is developed, devoid of aberrant splice sites, to transduce hematopoietic stem and progenitor cells, providing safe and effective gene therapy for Diamond-Blackfan anemia syndrome.
The lentiviral vector effectively alleviates DBAS-like phenotypes in vitro and in vivo, achieving polyclonal integration without clonal dominance or aberrant splicing, offering a potential cure with reduced long-term toxicity.