CellsMay 27, 2026

Progress of gene therapy for sickle cell disease: from molecular advances to patient care

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated May 30, 2026

Abstract

In 2023, two autologous gene therapy products for sickle cell disease received approval, marking a significant advancement in treatment options.

Sickle cell disease is linked to recurrent pain crises, organ damage, and reduced life expectancy.
Allogeneic stem cell transplants are limited by donor availability and associated risks.
Gene therapies like exa-cel and lovo-cel aim to increase fetal hemoglobin levels and modify the β-globin gene.
Clinical evidence suggests these therapies may provide durable disease modification with manageable short-term side effects.
Barriers to gene therapy access include financial, ethical, and psychosocial factors affecting both high-income and low-income regions.
Future research should focus on long-term safety, effectiveness comparisons, and treatment for younger patients.

Simplified

Sickle cell disease (SCD) is a monogenic disorder responsible for recurrent vaso-occlusive crises, progressive organ damage, and shortened life expectancy. For decades, allogeneic hematopoietic stem cell transplantation from a matched sibling donor has been the only established cure, but its reach remains limited by donor availability and transplant-related toxicity. The approval of two autologous gene therapy products in 2023, exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel), marked a turning point for the SCD population and the gene therapy field in general. This review proposes a molecular rationale for fetal hemoglobin reactivation and β-globin gene addition, describes the engineering of lentiviral and CRISPR-based platforms, and highlights the clinical evidence accumulated to date that demonstrated durable disease modification with acceptable short-term toxicity. We then assess the clinical positioning of gene therapy within the broader spectrum of curative options compared to current available treatments and address the financial, ethical and psychosocial barriers that limit access to gene therapy both within high-income countries and globally. Critical research priorities include long-term safety surveillance, comparative effectiveness studies, pediatric trials below 12 years, and validated patient-reported outcome instruments. Base editing, non-genotoxic conditioning, and in vivo delivery represent the most promising avenues to broaden access and reduce treatment burden.

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Funding

Competing interests

S.F. has received consulting fees from Bristol Myers Squibb, Pfizer, NovoNordisk, and Vertex. T.P. has received a Clinician Research Scholar from the FRQ (Fonds de Recherche du Québec) and research funding from Biossil Inc. The other authors declare no conflicts of interest.

PubMed

Progress of gene therapy for sickle cell disease: from molecular advances to patient care

Abstract

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Funding

Competing interests

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Abstract

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Funding

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Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the crispr gene editing brief