Challenges and opportunities for conceiving genetically diverse sickle cell mice.

Abstract

A milestone in sickle cell disease (SCD) therapeutics was achieved in December 2023 with the FDA-approved gene therapy for patients aged 12 years and older. However, these therapies may only suit a fraction of patients because of cost or health risks. A better understanding of SCD outcome heterogeneity is needed to propose patient-specific pharmacological interventions. To achieve this, humanized and genetically diverse mouse models are essential for associating candidate genotypes with specific hematological traits, organ function, and disease resilience. Here, we discuss the challenges and opportunities in developing genetically diverse sickle cell mice (GDS mice). These models are expected to complement current approaches in SCD research and enhance our understanding of SCD heterogeneity and anemia.