Gene therapy supports long-term reconstitution of patient hematopoietic stem cells in deficiency of adenosine deaminase 2.

ABSTRACT: Deficiency of adenosine deaminase 2 (DADA2) is a monogenic autoinflammatory disorder characterized by systemic inflammation, vasculopathy, immunodeficiency, and bone marrow failure. Current therapies-including anti-TNF agents and allogeneic hematopoietic stem cell transplantation (HSCT)-have limitations, especially for patients with hematologic involvement or no matched donor. We developed a lentiviral vector (LV.ADA2) to restore ADA2 expression in patient hematopoietic stem and progenitor cells (HSPCs) and evaluated its safety and efficacy in preclinical models. LV.ADA2 transduction of mobilized peripheral blood HSPCs from healthy donors resulted in stable ADA2 expression and secretion without impairing clonogenicity, multilineage differentiation, or long-term engraftment in immunodeficie

SUBMITTER: Rigamonti C 

PROVIDER: S-EPMC12662005 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature