bioRxiv : the preprint server for biologyJul 17, 2026

Improved β-thalassemia treatment using protected blood stem cell transplant with toxin-free preparation and natural selection inside the body

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

Updated Jul 18, 2026

Abstract

A new CD117-blocking monoclonal antibody (CIM058) has shown potency in blocking wild-type hematopoietic stem and progenitor cells (HSPCs).

Ex vivo gene therapy and genome engineering of HSPCs could provide one-time cures for certain conditions.
Toxic conditioning, particularly the use of busulfan, presents a significant safety concern for hematopoietic stem cell transplantation.
CIM058 was generated to specifically block CD117, a target previously identified as promising for antigen-specific therapy.
Combining CIM058 with engineered CD34+ HSPCs resistant to this antibody improved disease outcomes in a beta-thalassemia model.
This approach may reduce the need for myeloablative conditioning regimens, potentially lowering associated morbidities.

Simplified

Clinical evidence demonstrates that ex vivo gene therapy and genome engineering of hematopoietic stem and progenitor cells (HSPCs) could represent one-time cures. However, while genome editing itself has become increasingly efficient and precise, the toxic conditioning required for hematopoietic stem cell transplantation remains a major barrier to broad clinical implementation of these otherwise curative therapies. In particular, the use of busulfan for myeloablative conditioning constitutes a major safety concern. While preclinical studies established CD117 as a promising target for antigen-specific therapy, clinical translation faced setbacks balancing efficacy and safety. To overcome current limitations, we generated a new CD117-blocking monoclonal antibody (CIM058) and demonstrate its potency to block wild-type HSPCs. To enable long-term blockade of host HSPCs even after transplantation, we used prime editing to engineer CIM058-resistant human CD34 ⁺ HSPCs. When combined, CIM058 and the epitope engineered CD34 ⁺ HSPCs ameliorated disease phenotype in a β-thalassemia model. Our results suggest that this approach may overcome the reliance on busulfan or other myeloablative conditioning regimens with their associated morbidities, and by enabling toxin-free conditioning and in vivo selection of edited cells, may facilitate clinical implementation of these highly valuable genetic therapies.

Full Text

Full text is available at the source.

View Full Text ↗

Improved β-thalassemia treatment using protected blood stem cell transplant with toxin-free preparation and natural selection inside the body

Abstract

Full Text

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

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