Genome Editing Strategies for Inherited Bone Marrow Failure and Rare Hematologic Syndromes

Inherited bone marrow failure syndromes (IBMFS) and rare hematologic disorders—such as Diamond–Blackfan anemia, Shwachman–Diamond syndrome, congenital neutropenias, and related conditions—cause chronic cytopenias, transfusion dependence, and a heightened risk of myeloid malignancies and other cancers. In adult practice, these disorders often intersect with clonal hematopoiesis, myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML), creating complex diagnostic and therapeutic challenges. Current standards of care, including supportive management and allogeneic hematopoietic stem cell transplantation (HSCT), remain constrained by donor availability, treatment toxicity, and incomplete long‑term disease control.

Rapid advances in genome editing—spanning CRISPR–Cas systems, base and prime editing, and novel RNA‑guided platforms—offer new opportunities to correct pathogenic variants or rewire disease‑relevant pathways in hematopoietic stem and progenitor cells (HSPCs). To reach the clinic safely, these approaches must be informed by deep knowledge of disease biology, robust preclinical modelling, and clinically meaningful endpoints.

This Research Topic aims to bridge basic genome engineering with clinical hematology for inherited bone marrow failure and rare hematologic syndromes across the lifespan.

We welcome submissions that include, but are not limited to:

Mechanistic studies of IBMFS and rare hematologic syndromes that identify targets for genome editing or clarify progression to MDS/AML

Development, optimization, and benchmarking of CRISPR–Cas, base editing, prime editing, and related tools in human HSPCs and relevant model systems (including zebrafish, murine, and organoid models)

Ex vivo editing with autologous transplantation, and in vivo delivery approaches (viral and non‑viral vectors, nanoparticles, bone marrow niche targeting)

Strategies for variant correction, gene addition, or pathway modulation that restore hematopoiesis or prevent leukemic transformation

Preclinical studies defining lineage output, clonal dynamics, and long‑term engraftment, particularly in malignancy‑prone backgrounds

Integrated assessments of off‑target effects, genomic integrity, and genotoxicity, with read‑outs relevant to clonal evolution, MDS, and AML

Early‑phase clinical trial design, real‑world cohort studies, and translational frameworks for bringing genome‑edited therapies into routine hematology practice

Patient‑centred outcomes, including quality of life, treatment burden, and equity of access, as well as ethical and regulatory considerations in rare inherited disorders

By bringing together clinicians, genome engineers, stem cell biologists, and trialists, this Research Topic aims to define realistic routes to safe, durable, and clinically meaningful genome editing therapies for inherited bone marrow failure and rare hematologic syndromes.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Systematic Review

Keywords: Inherited bone marrow failure, Rare hematologic syndromes, Genome editing, Hematopoietic stem and progenitor cells, CRISPR-based therapies

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.