CRISPR-Cas9 Technology in the Treatment of Sickle Cell Anemia (SCA)

Abstract

Sickle cell anemia (SCA) is a monogenic inherited disease caused by a single point mutation in the HBB gene. Traditional treatments are ineffective in fundamentally correcting the genetic defect. In recent years, CRISPR-Cas9, an emerging gene editing technology, has shown great potential in the treatment of SCA. This article systematically reviews the mechanism of action of CRISPR-Cas9 and compares it with other editing tools. We focus on its application in SCA treatment, including strategies such as repairing the HBB gene mutation or targeting the HBG1/2 promoter to activate fetal hemoglobin. Furthermore, based on data from cell-based experiments, animal models, and clinical trials, we discuss the efficacy and limitations of representative therapies such as CTX001, Casgevy, and Lyfgenia. Results have shown that CRISPR-Cas9 can significantly improve red blood cell function in patients, and some therapies have received clinical approval, marking a significant breakthrough in its transition from laboratory research to clinical application. However, challenges remain, such as off-target effects, insufficient delivery efficiency, high treatment costs, and transplant-related complications, which need to be addressed. In the future, emerging strategies such as RNA editing are expected to expand into broader areas, including tumor treatment, while improving safety, providing safer and more accessible treatment options for monogenic diseases such as SCA.