ENGINEERING CRISPR BASE EDITING TECHNOLOGIES FOR TREATMENT OF INHERITED BLOOD DISORDERS

Abstract

Background: Inherited blood disorders such as sickle cell disease (SCD) and β-thalassemia are caused by single-gene mutations that disrupt normal hemoglobin synthesis and red blood cell function. Standard therapies such as bone marrow transplantation and lifelong transfusions are still limited by donor availability, immune complications and treatment-related toxicity. Recent advances in CRISPR base editing technologies enable precise genome modification without inducing double-stranded DNA breaks, which in turn reduces genomic instability and off-target effects.

Objective: To evaluate engineered CRISPR base editing systems for correction of pathogenic mutations associated with inherited blood disorders.

Methods: It applied adenine base editors (ABEs) and cytosine base editors (CBEs) to correct β-globin gene mutations in hematopoietic stem cells. We evaluated editing efficiency, hemoglobin restoration, and genomic safety by next-generation sequencing, flow cytometry, and functional erythroid differentiation assays.

Findings: Base editing resulted in ~78–85% mutation correction efficiency and <2% detectable off-target activity. The treated cells exhibited 65% increase of functional haemoglobin expression and a significant improvement of erythroid maturation compared to untreated controls.

Conclusions:  Engineered CRISPR base editing is a promising therapeutic approach for inherited blood disorders that could achieve precise, efficient and potentially curative genome correction with improved safety profiles.