Using Crisper in the Treatment of Sickle Cell Disease

Abstract

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.