Freja Kjellaug Amalia Ekman

All Publications

• Engineered hematopoietic stem cells give rise to therapeutic antibody secreting B cells. Research square Porteus, M., Luna, S., Feist, W., Utz, A., Afaghani, J., Miyauchi, M., Ghanim, H., Ekman, F., Amaya, A., Selvaraj, S., Russkamp, N., Schmiderer, L. 2026

  Abstract

  Monoclonal antibodies represent half of the top ten selling drugs. Their proven efficacy, however, generally requires repeated administration for prolonged periods of time. In contrast, cell-based therapies offer a different set of pharmacokinetics and pharmacodynamics than traditional medicines, including the potential to have lifetime durability after a single infusion. Here, we describe a genome-engineered stem cell-based platform for continuous antibody production from a single dose. Using CRISPR/Cas9 homology-directed repair mediated editing, we precisely integrated therapeutic antibody expression cassettes into a safe-harbor locus of hematopoietic stem and progenitor cells (HSPCs). Upon differentiation, these gene-targeted HSPCs generate B cells that secrete monoclonal antibodies. We validated this platform using two clinically approved antibodies, achieving efficient targeted integration of the gene-targeted antibodies (GT-Ab) in human HSPCs that successfully engraft in immunodeficient mice. Direct engineering of human B cells demonstrated robust secretion of therapeutic antibodies. To evaluate in vivo antibody production, we transplanted engineered GT-Ab murine HSPCs into immunocompetent mice, achieving durable serum antibody concentrations within the therapeutic range over several months. Lastly, by fusing the antibody to a destabilization domain, we enabled tunable antibody secretion via small molecule regulation. This modular platform establishes a potentially curative approach for chronic diseases currently reliant on repeated antibody administration, offering durable antibody production from a single treatment.

  View details for DOI 10.21203/rs.3.rs-9269825/v1

  View details for PubMedID 41994105

  View details for PubMedCentralID PMC13082165

• Reflections in focus: a qualitative Photovoice-informed study on pediatric patient and caregiver hospital experiences. BMC pediatrics Ekman, F. K., Torto, N. M., Hu, K., Bowman, C., Fariyike, O. A., Yates, J. J., Payra, S., Khalil, C. B., Yoseph, E. T., Ings, R. M., Reed, R. E., Rodriguez, S. T. 2026

  View details for DOI 10.1186/s12887-025-06281-5

  View details for PubMedID 41514233

• Engineered Hematopoietic Stem Cells Give Rise to Therapeutic Antibody Secreting B Cells Luna, S., Feist, W., Utz, A., Ghanim, H., Miyauchi, M., Selvaraj, S., Amaya, A., Ekman, F., Russkamp, N., Schmiderer, L., Porteus, M. CELL PRESS. 2025

  View details for Web of Science ID 001493880500122

• Allele-Specific CRISPR/AAV6 Gene Correction of Dominant <i>JAK2</i>-V617F Mutation in Polycythemia Vera Ekman, F., Selvaraj, S., Gotlib, J., Cromer, K., Porteus, M. CELL PRESS. 2025

  View details for Web of Science ID 001521594200088

• Engineering synthetic signaling receptors to enable erythropoietin-free erythropoiesis. Nature communications Shah, A. P., Majeti, K. R., Ekman, F. K., Selvaraj, S., Sharma, D., Sinha, R., Soupene, E., Chati, P., Luna, S. E., Charlesworth, C. T., McCreary, T., Lesch, B. J., Tran, T., Chu, S. N., Porteus, M. H., Kyle Cromer, M. 2025; 16 (1): 1140

  Abstract

  Blood transfusion plays a vital role in modern medicine, but frequent shortages occur. Ex vivo manufacturing of red blood cells (RBCs) from universal donor cells offers a potential solution, yet the high cost of recombinant cytokines remains a barrier. Erythropoietin (EPO) signaling is crucial for RBC development, and EPO is among the most expensive media components. To address this challenge, we develop highly optimized small molecule-inducible synthetic EPO receptors (synEPORs) using design-build-test cycles and genome editing. By integrating synEPOR at the endogenous EPOR locus in O-negative induced pluripotent stem cells, we achieve equivalent erythroid differentiation, transcriptomic changes, and hemoglobin production using small molecules compared to EPO-supplemented cultures. This approach dramatically reduces culture media costs. Our strategy not only addresses RBC production challenges but also demonstrates how protein and genome engineering can introduce precisely regulated cellular behaviors, potentially improving scalable manufacturing of a wide range of clinically relevant cell types.

  View details for DOI 10.1038/s41467-025-56239-5

  View details for PubMedID 39880867

  View details for PubMedCentralID 5355882

• Targeting the <i>JAK2</i>-V617F Mutation in Polycythemia Vera Using CRISPR/AAV6 Genome Editing Ekman, F., Selvaraj, S., Gotlib, J., Cromer, M., Porteus, M. H. ELSEVIER. 2024: 4524-4525

  View details for DOI 10.1182/blood-2024-211120

  View details for Web of Science ID 001412530900020

• High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition. Nature biotechnology Selvaraj, S., Feist, W. N., Viel, S., Vaidyanathan, S., Dudek, A. M., Gastou, M., Rockwood, S. J., Ekman, F. K., Oseghale, A. R., Xu, L., Pavel-Dinu, M., Luna, S. E., Cromer, M. K., Sayana, R., Gomez-Ospina, N., Porteus, M. H. 2023

  Abstract

  Therapeutic applications of nuclease-based genome editing would benefit from improved methods for transgene integration via homology-directed repair (HDR). To improve HDR efficiency, we screened six small-molecule inhibitors of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key protein in the alternative repair pathway of non-homologous end joining (NHEJ), which generates genomic insertions/deletions (INDELs). From this screen, we identified AZD7648 as the most potent compound. The use of AZD7648 significantly increased HDR (up to 50-fold) and concomitantly decreased INDELs across different genomic loci in various therapeutically relevant primary human cell types. In all cases, the ratio of HDR to INDELs markedly increased, and, in certain situations, INDEL-free high-frequency (>50%) targeted integration was achieved. This approach has the potential to improve the therapeutic efficacy of cell-based therapies and broaden the use of targeted integration as a research tool.

  View details for DOI 10.1038/s41587-023-01888-4

  View details for PubMedID 37537500

  View details for PubMedCentralID 3694601