Science Highlights
Published on January 21, 2025
Using an autologous lentivirally barcoded HSPC transplantation model to measure long-term quantitative clonal dynamics
by BJHaem
Hosuru RV, Yang J, Zhou Y, et al. Long-Term Tracking of Haematopoietic Clonal Dynamics and Mutations in Non-Human Primate Undergoing Transplantation of Lentivirally Barcoded Haematopoietic Stem and Progenitor Cells. British Journal of Haematology. 2024; (doi: 10.1111/bjh.19889).
More than a decade of animal data culled from a hematopoietic stem and progenitor cell (HSPC) transplantation model is giving scientists insight into long-term clonal dynamics and other safety and durability metrics associated with the approach. This type of autologous gene therapy has promising implications for multiple blood disorders, including sickle cell disease and thalassemia, but new evidence has emerged around potential risks for clonal expansions and myeloid malignancies. Understanding provided by predictive models is critical to prepare for broader-scale application of the technology in people. For optimal relevance to the human experience, the HSPC model included five healthy, young rhesus monkeys who underwent total body irradiation and then transplantation of autologous HSPCs transduced with a lentiviral vector. Researchers then quantitatively tracked clonal output of hundreds of thousands of transduced HSPCs and their progeny in the test subjects using genetic barcoding. The results to date indicate minimal clonal succession after stable haematopoietic reconstitution and no evidence of accelerated acquisition of acquired somatic mutations following autologous lentivirally transduced HSPC transplantation.
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