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CRISPR-Cas12a Gene Editing of HBG1 and HBG2 Promoters to Treat β-Thalassemia - PubMed

21 hours ago
  • #β-thalassemia
  • #fetal hemoglobin
  • #CRISPR-Cas12a
  • Reni-cel is an investigational CRISPR-Cas12a gene-edited therapy targeting HBG1 and HBG2 promoters to reactivate fetal hemoglobin for treating transfusion-dependent β-thalassemia.
  • In a phase 1-2 study with nine participants, all achieved neutrophil engraftment within 42 days, showed rapid increases in total and fetal hemoglobin, and became transfusion-free at their last follow-up.
  • Six participants evaluable at 12 months or more were transfusion-independent, with mean hemoglobin levels >12 g/dL (total) and >11 g/dL (fetal) from months 6 to 18.
  • Safety: 69 grade 3/4 adverse events occurred, including six serious events (e.g., infections), largely consistent with myeloablative conditioning; one case of decreased lymphocyte counts was attributed to reni-cel.
  • The study was terminated early due to sponsor priorities, but results support further investigation of Cas12a gene editing for β-thalassemia.