Multiplex base editing of BCL11A regulatory elements to treat sickle cell disease.

Editing a γ-Globin Repressor Binding Site Restores Fetal Hemoglobin Synthesis and Corrects the Phenotype of Sickle Cell Disease Erythrocytes

Base Editing-Mediated Dissection of the -200 Region of the γ-Globin Promoters to Induce Fetal Hemoglobin and Rescue Sickle Cell Disease and β-Thalassemia

Two Is Better Than One: Fetal Hemoglobin Reactivation and Alpha-Globin Downregulation to Correct the β-Hemoglobinopathy Phenotype through Base Editing

Targeted Base Editing Strategies for Beta-Hemoglobinopathies

Editing the LRF Repressor Binding Site in the γ-Globin Promoters Induces Therapeutically Relevant Fetal Hemoglobin Levels for the Treatment of β-Hemoglobinopathies

CD117 Antibody Conditioning and Multiplex Base Editing Enable Rapid and Robust Fetal Hemoglobin Reactivation in a Rhesus Autologous Transplantation Model

Epitope Editing Combined with Extended Schedule Anti-KIT Antibody Treatment Allows Immune-Based In Vivo Selection of Multiplex Genome-Engineered Cells

Domain-Focused CRISPR-Cas9 Screen Identifies the E3 Ubiquitin Ligase Substrate Adaptor Protein SPOP as a Novel Repressor of Fetal Hemoglobin

Increased Potency and Uniformity of Fetal Hemoglobin Induction from Base Editing Compared to Cas9 Nuclease

Single Cell Analysis and Functional Features of Circulating CD34 + Cells from Patients with Sickle Cell Anaemia Unveil a Defect in the Myeloid Lineage

Individuals with sickle cell disease (SCD) experience many complications and health problems due to their mutated hemoglobin gene; however, these problems could be alleviated by using CRISPR gene editing to alter which hemoglobin variants hematopoietic stem progenitor cells produce. The aim of this review is to determine if it is safe and effective to treat patients with SCD with CRISPR. The findings of “CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β Thalassemia” found an increase in fetal hemoglobin expression in patients after transplanting hematopoietic stem progenitor cells with edits to the BCL11A transcription factor. “Genome editing using CRISPR-Cas9 to create the HPFH genotype in HSPCs: An approach for treating sickle cell disease and β-thalassemia” also raised fetal hemoglobin by editing hematopoietic stem progenitor cells within their β-globin loci to artificially apply a hereditary persistence of fetal hemoglobin deletional genotype to the cells. Researchers in “CRISPR/Cas9-Mediated Correction of the Sickle Mutation in Human CD34+ cells” raised wild-type hemoglobin expression in hematopoietic stem progenitor cells affected with SCD by editing the β-globin loci and “fixing” the point mutation that causes SCD. Target deletion efficiency ranged from 18%-80%, and every study used either SpCas9 or SaCas9. Each study found no punitive off-target effects, and they also succeeded in raising hematopoietic stem progenitor cells levels of their targeted hemoglobin. These results point to using CRISPR as both a safe and effective way to treat SCD.

Epitope Edited Hematopoietic Stem Cells Allow Immune-Based In Vivo Selection of Genome-Engineered Cells

Novel Genetic Loci That Influence Fetal Hemoglobin Expression in Children with Sickle Cell Anemia

Interrogating Post-Transcriptional Mechanisms of Fetal Hemoglobin Regulation

Objective. Elevated maternal levels of fetal hemoglobin (HbF) present a unique situation where both mother and fetus produce hemoglobin with equivalent oxygen affinities. We aimed to determine pregnancy outcomes in women with persistently elevated HbF.Methods. In this retrospective cohort study, women with HbF levels exceeding 10% were identified by searching a provincial database. Maternal, obstetric, and neonatal outcomes were extracted from chart reviews performed at two hospitals.Results. Twenty-two women with a total of 43 pregnancies and 33 live births were identified. Maternal levels of HbF ranged between 11 and 100%. Women with HbF ≥ 70% were significantly more likely to deliver growth-restricted or small for gestational age (SGA) fetuses compared to the group of women with HbF <70% (100% versus 8%; p <0.01). Three women (4/32 pregnancies) received blood transfusions, which was unrelated to HbF levels.Conclusions. Pregnancies complicated by maternal HbF levels ≥ 70% are at increased risk of intra-uterine growth restriction or SGA fetuses. Increased antenatal surveillance is suggested.