{
  "id": 8169768,
  "title": "In vivo HSPC gene therapy of hemoglobinopathies without drug selection of corrected cells",
  "url": "https://urgent.news/2026/09/17/in-vivo-hspc-gene-therapy-of-hemoglobinopathies-without-drug",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-09-17T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.15.751289v1?rss=1"
  },
  "original_language": "en",
  "account": "Researchers have developed a novel in vivo gene therapy technique for hemoglobinopathies that eliminates the need for pharmacologic selection of corrected cells. This approach utilizes base and prime editing to introduce a nonpathogenic EPOR variant into hematopoietic stem/progenitor cells (HSPCs), which then allows for the preferential expansion of gene-corrected erythroid cells. This method combines EPOR editing with three therapeutic strategies for correcting hemoglobinopathies: gamma-globin gene addition, gamma-globin reactivation, or correction of the sickle cell disease mutation. The therapy was delivered using tropism-modified helper-dependent adenoviral vectors that targeted HSPCs, allowing for simultaneous delivery of the EPOR-editing machinery and therapeutic components. In vitro studies in an erythroid progenitor cell line and primary CD34+ cells showed that the EPORW439* variant provided a significant proliferative advantage to the therapeutically modified erythroid progenitors. In mice genetically modified to mimic beta/thalassemia, the EPORW439*-mediated erythrocyte production of erythropoietin (EPO) hypersensitivity, combined with a therapeutic gamma-globin transgene, resulted in 70% HbF-positive erythroid cells and substantial reversal of the disease-associated phenotype. These improvements included reduced oxidative stress, near-complete elimination of splenic iron deposition, and reduced splenomegaly. Crucially, these beneficial effects were achieved with just a single intravenous administration of the vectors after mobilizing HSPCs and administering cytokine prophylaxis, without requiring any subsequent pharmacologic selection. This innovative gene-editing strategy holds promise for enhancing the therapeutic potential of in vivo HSPC gene therapy for hemoglobinopathies.",
  "summary": "In vivo hematopoietic stem/progenitor cell (HSPC) gene therapy remains limited by low gene-editing efficiency and a lack of clinically applicable selection strategies to enrich therapeutically corrected progeny. We used in vivo base and prime editing to introduce a nonpathogenic EPOR variant into HSPCs, conferring erythropoietin hypersensitivity and promoting preferential expansion of…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}