Hematopoietic stem cell gene therapy for the treatment of X-linked agammaglobulinemia
Year: 2025
Type: article
Abstract: cDNA transgene directly into its endogenous locus. To study the effectiveness of this therapy, murine lineage-negative hematopoietic cells from a murine model of XLA were edited using CRISPR-Cas9/rAAV6 then transplanted into recipient XLA mice. Myeloablated XLA mice that received transplantation of Btk-corrected Lin- cells displayed high levels of engraftment, significant increases in their B cell levels, increased production of various immunoglobulins, improved B cell development in the bone marrow, increased B cell receptor diversity, and the ability to produce antigen-specific antibodies following immunization. Collectively, we have modeled a gene therapy strategy in a disease model of XLA and extensively validated the site-specific genome editing approach.
Authors: Christopher R. Luthers, Annika Mittelhauser, Aurelien Colamartino, Xiaomeng Wu, Samuel Cirigliano, Joseph D. Long, Julie M. Sanchez, Zulema Romero, Donald B. Kohn
Institution: University of California, Los Angeles
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,900
Funders: California Institute for Regenerative Medicine, Immune Deficiency Foundation, California Institute of Regenerative Medicine, National Academy of Sciences, University of California, Los Angeles, Division of Graduate Education, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles
Award: G5884708920
OpenAlex ID: W4413191797