Abstract
Purpose
Sickle Cell Disease (SCD) is a monogenic, autosomal recessive disorder caused by mutations in the β-globin gene, resulting in the production of abnormal hemoglobin S (HbS). When deoxygenated HbS polymerizes, it causes red blood cells to become sickle-shaped, and prone to hemolysis. These abnormal and sickled cells obstruct small blood vessels, leading to vaso-occlusion and tissue ischemia, contributing to multiple complications. SCD impacts nearly 8 million people worldwide, and is estimated to affect 500,000 newborns annually. Historically, potentially curative therapies have been limited, but advances in fetal diagnosis and gene-editing technologies have highlighted the potential use of in utero gene therapy as a strategy to correct the β-globin mutation before clinical disease onset. This scoping review summarizes the current evidence on in utero and fetal gene-editing strategies for SCD.