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RevM10-transduced hematopoietic stem cells are autologous hematopoietic stem and progenitor cells genetically modified ex vivo with a retroviral vector to express RevM10, a dominant-negative mutant of the HIV-1 Rev regulatory protein that blocks nuclear export of unspliced and singly spliced viral RNAs and thereby inhibits production of infectious virions.[1][5][7] These gene-modified stem cells are reinfused in HIV-1–infected patients with AIDS-related disease (including lymphoma) to reconstitute a progeny pool of CD4+ T cells and other lineages that are intrinsically resistant to HIV-1 replication, with the goal of achieving durable viral control and immune reconstitution as a functional cure strategy.[1][2][5] Early Phase I/II trials by Systemix and collaborators used RevM10-transduced CD34+ hematopoietic stem/progenitor cells (sometimes combined with an antisense HIV-1 pol construct) without or with myeloablative chemotherapy and peripheral blood stem cell transplantation, demonstrating feasibility and safety but only low-level, transient gene marking in vivo and thus limited clinical impact on viral load.[1][2][5][6]
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