Sickle cell disease

Byaibio

Sickle cell disease is an inherited blood disorder and a major indication for several therapies, including exagamglogene autotemcel, hydroxyurea, red blood cell transfusions, and the investigational renizgamglogene autogedtemcel. Its core pathobiology involves abnormal erythroid biology and vaso-occlusive complications, and recent gene-editing work has focused on CRISPR-Cas12a disruption of the hbg1 and hbg2 promoters to reactivate fetal hemoglobin. The disease has also been studied as a setting for immune complications, where erythroid cell-derived asparagine was elevated and modulation of asparagine altered RBC alloimmunization. In children with SCD, it is a recognized risk condition for invasive pneumococcal disease, supporting the role of pcv13 in prevention. Overall, recent literature spans gene editing, immunohematology, infection prevention, and health economics, including cost-effectiveness analyses of exagamglogene autotemcel for recurrent vaso-occlusive crises.

Gene editing and disease modification

  • A 2026 NEJM study (PMID:41931047) reported CRISPR-Cas12a editing of the hbg1 and hbg2 promoters as a therapeutic strategy for sickle cell disease.
  • The disease was the target of an investigational CRISPR-Cas12a gene-edited therapy (PMID:41931047).
  • renizgamglogene autogedtemcel is designed for treatment of sickle cell disease, highlighting ongoing development of gene-editing approaches (PMID:41931047).
  • exagamglogene autotemcel is approved for patients with sickle cell disease with recurrent vaso-occlusive crises, underscoring clinical translation of gene editing (PMID:41730016).

Immunohematology and alloimmunization

  • In a 2026 Blood Advances study (PMID:41995734), erythroid cell-derived asparagine was elevated in sickle cell disease.
  • Modulating asparagine affected RBC alloimmunization, and asparaginase reduced alloimmunization in SCD mice (PMID:41995734).
  • asparaginase also inhibited plasma cell differentiation in this model, linking amino-acid metabolism to antibody-mediated transfusion complications (PMID:41995734).
  • src family kinase activation was reduced by ASNase treatment in SCD, suggesting a signaling component to the observed effect (PMID:41995734).

Infection prevention and supportive care

  • A 2026 systematic review (PMID:41560367) identified sickle cell disease as a pediatric risk condition for invasive pneumococcal disease.
  • pcv13 introduction was associated with a relative reduction in invasive pneumococcal disease due to any serotype in children with risk conditions, including SCD (PMID:41560367).
  • These findings support vaccination as part of preventive care in a high-risk subgroup with chronic hemolytic disease (PMID:41560367).
  • Standard care for sickle cell disease includes symptomatic care, hydroxyurea, and/or red blood cell transfusions (PMID:41730016).

Clinical outcomes and health economics

  • A 2026 Journal of Medical Economics analysis (PMID:41730016) evaluated the cost-effectiveness of exagamglogene autotemcel in patients with sickle cell disease and recurrent vaso-occlusive crises.
  • The analysis focused on clinical outcomes relevant to recurrent vaso-occlusive crises, a key disease burden in SCD (PMID:41730016).
  • This work complements approval of exagamglogene autotemcel and broader efforts to quantify value for gene-edited therapies in SCD (PMID:41730016).
  • Together with standard-of-care options, these studies reflect a shift from symptom control toward disease-modifying and potentially curative strategies (PMID:41730016).