Jiwon Jun

Advancing Gene Therapy in Sickle Cell Disease: Exploring the Potential of Prime Editing

Started June 28, 2024

Abstract or project description

Sickle cell disease (SCD) is a prevalent genetic disorder caused by a mutation in the HBB gene, leading to the production of abnormal hemoglobin that can block blood flow and cause severe pain. While conventional treatments for SCD are available, they have several limitations and are often not curative. As a result, gene therapy has emerged as a promising alternative for SCD treatment. CASGEVY, a gene therapy using CRISPR-Cas9 technology, has shown success in reducing symptoms of SCD by knocking out BCL11A and increasing fully functional, fetal hemoglobin. However, CASGEVY is prohibitively expensive and has some risks and inconveniences that limit its broader use. Prime editing, a newer gene editing technique, is considered more precise and potentially safer as it can be used to directly correct the HBB mutation. Additionally, unlike CASGEVY, prime editing could be used in vivo to correct the SCD mutation within the bone marrow. Recent studies have shown that prime editing can effectively correct the mutation both ex vivo and in vivo. Since in vivo prime editing could be more practical and affordable for people around the world, including in sub-Saharan Africa where SCD is most common, further research is needed to improve the efficiency and safety of prime editing to make it applicable to patients suffering from SCD globally. Here, we review the current application of CRISPR-Cas9 and prime editing for SCD treatment and explore further opportunities to enhance prime editing.