Impacting millions around the world annually, sickle cell disease (SCD) arises from a point mutation in the HBB gene that drives abnormal adult hemoglobin formation and sickled red blood cells. Therapeutic strategies often target reactivation of fetal hemoglobin (HbF) to bypass the defective adult form.​

​A recent CRISPR screen from the Khandros Lab, in collaboration with the Junwei Shi Lab, identified the BAF chromatin remodeler complex as a potential activator of HbF transcription. However, conventional genetic knockouts of BRG1 are embryonic lethal in mice, limiting the ability to study its direct role without confounding adaptive responses. To overcome this limitation, we employed the PROTAC (Proteolysis-Targeting Chimera) ACBI1, which acutely degrades essential BAF components BRG1 (SMARCA4), BRM (SMARCA2), and PBRM1. Here, we present a dose titration of ACBI1 to evaluate its effects on BRG1 degradation in two distinct erythroid model systems, establishing a platform for dissecting BAF’s role in the regulation of fetal hemoglobin expression.​