Hematology reportsJan 21, 2026

New Developments in Gene Therapy for Inherited Blood Disorders Affecting Hemoglobin

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

Updated Jan 22, 2026

Abstract

Lentiviral gene addition approaches have achieved transfusion independence in β-thalassaemia patients and significant reductions in vaso-occlusive events in sickle cell disease patients.

Haemoglobinopathies, such as β-thalassaemia and sickle cell disease, are prevalent monogenic disorders associated with high morbidity and early mortality.
Traditional treatments focus on symptom management but do not correct the genetic defects causing these diseases.
Allogenic haematopoietic stem cell transplantation is the only established curative option but carries substantial risks.
Gene therapy has transitioned from experimental proof-of-concept to approved therapies, demonstrating durable expression of functional β-like globin transgenes.
Gene silencing strategies targeting BCL11A and gene editing technologies like CRISPR/Cas9 have led to new approved therapies for these conditions.
Access to gene therapy is currently limited by manufacturing challenges, conditioning regimens, and treatment costs.

Simplified

Haemoglobinopathies, including β-thalassaemia and sickle cell disease (SCD), are among the most common monogenic disorders worldwide and remain major causes of morbidity and early mortality. Historically, management of these life-altering diseases has relied on supportive treatment and symptom management and, although these treatments reduce symptoms and ease disease burden, they do not correct the underlying genetic defect. Allogenic haematopoietic stem cell transplantation (HSCT) has been the only established curative option; however, it comes with substantial risks that significantly restrict its applicability. Over the past two decades, haematopoietic stem cell (HSC) gene therapy for haemoglobinopathies has rapidly progressed from experimental proof-of-concept to approved therapies. Lentiviral gene addition approaches have demonstrated durable expression of functional β-like globin transgenes, achieving transfusion independence in β-thalassaemia patients and significant reductions in vaso-occlusive events in SCD patients. Alternative therapeutic approaches to promote HbF expression have proved to be highly successful. Gene silencing strategies targeting BCL11A have been successful clinically and, more recently, gene editing technologies such as CRISPR/Cas9 have enabled precise disruption of regulatory elements controlling γ-globin repression, leading to the approval of the first CRISPR-based therapy for SCD and β-thalassaemia. Emerging base editing technologies promise even more precise genetic modification and are advancing through clinical evaluation. Despite these advances, access to gene therapy remains restricted due to the need for highly specialised manufacturing, toxic myeloablative conditioning regimens, and high treatment costs. Ongoing improvements and adaptations in these areas are essential to ensure that gene therapies fulfil their potential as accessible, curative treatments for patients suffering from haemoglobinopathies worldwide.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

H.B.G. is an employee of Orchard Therapeutics. The authors declare no conflicts of interest.

PubMed

New Developments in Gene Therapy for Inherited Blood Disorders Affecting Hemoglobin

Abstract

Full Text

Funding

Competing interests

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

Abstract

Full Text

Funding

Competing interests

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