Base editing is a next-generation, CRISPR-based gene editing technology that makes precise conversion of one nucleobase to another by virtue of a human deaminase enzyme, directly on the gene, without making double-stranded breaks. Using this technology, we are developing two therapeutic products, BEAM-101 and BEAM-102, for the treatment of Sickle Cell Disease (SCD). In the case of BEAM-101, we are using the precision of base editing to reproduce point mutations in the promoter of the human gamma 1 and gamma 2 genes that are normally seen in individuals who have a condition known as Hereditary Persistence of Fetal Hemoglobin (HPFH). These individuals retain high levels of expression of the fetal hemoglobin (HbF) in adulthood and, because of this, they are protected from mutations in the beta globin gene that would otherwise cause sickle cell disease. BEAM-101 has been shown to achieve the highest level of HbF reported pre-clinically so far (65%) and is progressing to clinical studies. BEAM-102 directly corrects the single amino acid Valine that causes the cells to sickle under low oxygen conditions. For BEAM-102, we have engineered a novel base editor, where the active site of the deaminase has been inlaid directly within the CAS protein. Using this editor we are able to convert the Valine at position 6 into an Alanine, thus converting the sickling form of hemoglobin (HbS) to a normal variant known as HbG Makassar, which occurs in ~0.1% of the human population, with greater than 80% efficiency.