Sickle cell disease-specific barriers to in vivo hematopoietic stem cell gene therapy

Gene therapy for individuals living with sickle cell disease is a transformative therapy, ameliorating many of its severe symptoms. Nevertheless, ex vivo administration of gene therapy coupled with sickle cell disease specific obstacles, complicate and limit widespread adoption. In this review, we discuss current strategies to develop in vivo gene delivery technologies, highlighting different approaches and their potential benefits and limitations in the context of sickle cell disease. Additionally, we examine editing challenges and outline how in vivo gene editing may be evaluated for therapeutic benefit.