Cellectis Publishes a Novel Intronic Gene Editing Approach For the Treatment of Inborn Metabolic Diseases by Edited HSPCs

Published on April 10, 2024

Back to all press releases


New York, NY – April 10, 2024 – Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, announced today the publication of a new research paper in Molecular Therapy, demonstrating that TALEN-mediated intron editing of hematopoietic stem and progenitor cells (HSPCs) enables transgene expression restricted to the myeloid lineage. This approach could unlock new therapeutic avenues for the treatment of inborn metabolic diseases as well as neurological diseases that require delivery of therapeutics to the brain.

About HSPCs

Gene editing in hematopoietic stem and progenitor cells (HSPCs) has enabled the treatment of multiple previously uncurable genetic diseases. Edited therapeutic HSPCs can engraft in the patient’s bone marrow, self-replicate, differentiate and populate other organs, propagating the therapeutic effects systemically and indefinitely after a single intervention.

In this paper, Cellectis developed an intron-specific gene insertion strategy for HSPC, that restricts the expression of a therapeutic protein named IDUA to the myeloid lineage. Edited myeloid cells then act as a Trojan horse to vectorize IDUA across the blood brain barrier and thus, its delivery to the brain. This gene insertion strategy displays minimal genomic footprint and prevents the expression of IDUA by stem cells or other non-myeloid differentiated cells. It could potentially enable the development of efficient therapies for both metabolic and neurological disorders.

“This novel TALEN® mediated-intron editing approach rewires the natural ability of myeloid cells to cross the blood brain barrier to efficiently vectorize a genetically encoded-therapeutic protein to the brain. In addition, by inserting the therapeutic transgene in an intronic region of the targeted gene, this approach preserves endogenous gene expression and thus, mitigates the common adverse events observed after gene insertion. This approach is, by essence, versatile and could be used to vectorize an array of therapeutic proteins to the brain and potentially address multiple neurological disorders” commented Julien Valton, Ph.D., Vice President of Gene Therapy at Cellectis.

Research data showed that:

  • The CD11b intronspecific gene insertion approach efficiently restricts the expression of a desired transgene to the myeloid lineage, preventing its overexpression by stem cells or by other differentiated lineages.
  • The insertion of an IDUA transgene in the first intron of the CD11b gene enables to express IDUA (the enzyme missing in Mucopolysaccharidosis type I patients), in a myeloidspecific manner without affecting CD11b endogenous expression.
  • Edited HSPC exhibited robust engraftment in the bone marrow of immunodeficient mice, displayed multi-lineage differentiation in various hematopoietic tissues and showed significant presence in the brain as myeloid cells.

The article is available on Molecular Therapy website by clicking on this link:


Download the PDF file