Immungenetik | Universitätsklinikum Tübingen

AG “Cell and Gene Therapy“

Research Topics

Hematopoietic stem cell gene therapy for the treatment of β-hemoglobinopathies
Hematopoietic stem cell gene therapy with CRISPR/Cas9 mRNA and AAV6 vector in metachromatic leukodystrophy
Development of novel mRNA-based therapy strategies targeting rhabdoid tumors
CRISPR/Cas9-boosted improvements in CAR-T and CAR-NK cell-based immunotherapy for cancer treatment
Lipid nanoparticles (LNPs) for ex vivo editing of hematopoietic stem cells and immune effector cells

Funding and Publication

Lead

frontend.sr-only_#{element.icon}: Prof. Dr. med. Dr. rer. nat. Dipl. Biol. Markus Mezger Group leader

E-Mail-Adresse: markus.mezger@med.uni-tuebingen.de

frontend.sr-only_#{element.icon}: Dr. rer. nat. Justin Selvaraj
Associated advisor

E-Mail-Adresse: justin.selvaraj@med.uni-tuebingen.de

frontend.sr-only_#{element.icon}: Dr. Tahereh Mohammadian Gol Postdoc

E-Mail-Adresse: Tahereh.Mohammadian-Gol@med.uni-tuebingen.de

Gene therapy

Our team is primarily working in the field of hematopoietic stem cell transplanation (HSCT). By utilizing various cell and gene therapy approaches, we aim to develop novel gene therapy modalities for β- hemoglobinopathies (β-thalassemia, sickle cell disease), cancer immunotherapy, and rare diseases including metachromatic leukodystrophy and immunodeficiency. Our technologies include lentiviral (LV) and Adeno-associated virus (AAV) gene transfer, mRNA therapeutics, adoptive immune cell therapy, genome editing and gene correction using CRISPR / Cas9 system.

(Lamsfus Calle et al., 2019, Blood Reviews, https://doi.org/10.1016/j.blre.2019.100641)

(Ureña Bailén et al., 2019, Briefings in Functional Genomics, https://doi.org/10.1093/bfgp/elz039)

(Daniel Moreno et al., 2019, Bone Marrow Transplantation, https://doi.org/10.1038/s41409-019-0510-8)

Immunomodulation

As we focus on HSCT, in our research we are addressing a major adverse effect called graft versus host disease (GvHD), a serious complication after allogeneic stem cell transplantation. To achieve this goal, we are utilizing donor’s immune cells including mesenchymal stromal cells, myeloid suppressor cells and regulatory T cells to better control immune reaction of the graft through immune modulation.

KIR Genotyping

We are employing state-of-the-art technologies including sequencing, fragment analysis, droplet digital PCR (ddPCR) and developing innovative methods in order to identify optimized stem cell donors, and improving previous diagnostic routine assays for chimerism analysis, KIR genotyping and minimal residual disease (MRD) analysis.

Laboratory for chimerism analysis and KIR genotyping

Funding and Publication

Fortüne Programm Tübingen
Clinician Scientist Programm Tübingen
IZKF Tübingen
José Carreras Leukämie-Stiftung e. V.
Förderverein für krebskranke Kinder Tübingen e.V.
Stiftung des Fördervereins krebskranke Kinder Tübingen
Manchot Stiftung
DEBRA Austria
Bundesministerium für Bildung und Forschung
Deutsches Zentrum für Infektionsforschung
Stefan-Morsch Stiftung
Madeleine Schickedanz Stiftung

Zahedipour F, Sadeghianfard S, Wisser S, Dinarvand M, Steiner D, Ramesh A, Trosien P, Leibold J, Mezger M, Mohammadian Gol T (2026) Lipid Nanoparticle Delivery of CAR276 mRNA Enables Antigen-Specific Cytotoxicity in T Cells Against Glioblastoma Cells. Biomedicines 14(10):2365. doi: 10.3390/biomedicines14102365.
Carle MF, Mohammadian Gol T, Antony JS, Roig-Merino A, Carter ME, Lauer UM, Mezger M, Kloker LD (2025) Targeting Oncogenic Fusion-Driven NUT Carcinoma with CRISPR/Cas9 Genome Editing. Mol Ther Oncol. 33(4):201068. doi: 10.1016/j.omton.2025.201068
Zahedipour F, Gol TM, Wisser S, Ramesh A, Ureña-Bailén G, Jaafari MR, Mezger M (2025) Revolutionizing pediatric gene and cell therapy: The hope for lipid-based nanoparticles in blood disorders. Curr Res Transl Med. 73(4):103545. doi: 10.1016/j.retram.2025.103545
Handgretinger R, Mezger M (2024) An evaluation of exagamglogene autotemcel for the treatment of sickle cell disease and transfusion-dependent beta-thalassaemia. Expert Opin Biol Ther. 1-6. doi: 10.1080/14712598.2024.2399134
Mohammadian Gol T, Zahedipour F, Trosien P, Ureña-Bailén G, Kim M, Antony JS, Mezger M (2024) Gene therapy in pediatrics - Clinical studies and approved drugs (as of 2023). Life Science 348:122685. doi: 10.1016/j.lfs.2024.122685
Antony JS, Herranz AM, Mohammadian Gol T, Mailand S, Monnier P, Rottenberger J, Roig-Merino A, Keller B, Gowin C, Milla M, Beyer TA*, Mezger M* (2024) Accelerated generation of gene-engineered monoclonal CHO cell lines using FluidFM™ nano-injection and CRISPR/Cas9. Biotechnology Journal 19(4):e2300505. doi: 10.1002/biot.202300505
Mohammadian Gol T, Kim M, Sinn R, Ureña-Bailén G, Stegmeyer S, Gratz PG, Zahedipour F, Roig-Merino A, Antony JS, Mezger M (2023) CRISPR-Cas9-Based Gene Knockout of Immune Checkpoints in Expanded NK Cells. International Journal of Molecular Sciences 24(22), 16065. doi.org/10.3390/ijms242216065
Luib L, Kreyenberg H, Michaelis S, Handgretinger R, Mezger M (2023) Transferring measurable residual disease measurement in pediatric acute lymphoblastic leukemia from quantitative real-time PCR to digital droplet PCR. Pediatric Transplant 7:e14483. doi: 10.1111/petr.14483
Mohammadian Gol T, Ureña-Bailén G, Hou Y, Sinn R, Antony JS, Handgretinger R, Mezger M (2023) CRISPR medicine for blood disorders: Progress and challenges in delivery. Frontiers in Genome Editing 4:1037290. doi: 10.3389/fgeed.2022.1037290
Ureña-Bailén G*, Block M*, Grandi T, Aivazidou F, Quednau J, Krenz D, Daniel-Moreno A, Lamsfus-Calle A, Epting T, Handgretinger R, Wild S*, Mezger M* (2023) Automated Good Manufacturing Practice-Compatible CRISPR-Cas9 Editing of Hematopoietic Stem and Progenitor Cells for Clinical Treatment of β-Hemoglobinopathies. The CRISPR Journal 6(1):5-16. doi: 10.1089/crispr.2022.0086
Hou Y, Ureña-Bailén G, Mohammadian Gol T, Gratz PG, Gratz HP, Roig-Merino A, Antony JS, Lamsfus-Calle A, Daniel-Moreno A, Handgretinger R, Mezger M (2022) Challenges in Gene Therapy for Somatic Reverted Mosaicism of X-linked Combined Immunodeficiency by CRISPR/Cas9 and Prime Editing. Genes 13(12):2348. doi: 10.3390/genes13122348
Ureña-Bailén G, Dobrowolski JM, Hou Y, Dirlam A, Roig-Merino A, Schleicher S, Atar D, Seitz C, Feucht J, Antony JS, Mohammadian-Gol T, Handgretinger R, Mezger M (2022) Preclinical evaluation of CRISPR-edited CAR-NK-92 cells for off-the-shelf treatment of AML and B-ALL. International Journal of Molecular Sciences 23(21):12828. doi: 10.3390/ijms232112828
Antony J*, Daniel-Moreno A*, Lamsfus-Calle A, Raju J, Kaftancioglu M, Ureña-Bailén G, Rottenberger J, Hou Y, Santhanakumaran V, Lee J-H, Heumos L, Böhringer J, Krägeloh-Mann I, Handgretinger R, Mezger M (2022) A mutation-agnostic hematopoietic stem cell gene therapy for metachromatic leukodystrophy. The CRISPR Journal 5(1):66-79. doi: 10.1089/crispr.2021.0075
Hou Y, Gratz HP, Ureña-Bailén G, Gratz PG, Schilbach-Stückle K, Renno T, Güngör D, Mader DA, Malenke E, Antony JS, Handgretinger R, Mezger M (2021) Somatic Reversion of a Novel IL2RG Mutation Resulting in Atypical X-Linked Combined Immunodeficiency. Genes 13(1):35. doi.org/10.3390/genes13010035
Lamsfus-Calle A*, Daniel-Moreno A*, Ureña-Bailén G, Rottenberger J, Raju J, Epting T, Marciano S, Heumos L, Baskaran P, Antony J, Handgretinger R, Mezger M (2021) Universal gene correction approaches for β-hemoglobinopathies using CRISPR-Cas9 and AAV6 donor templates. The CRISPR Journal 4(2):207-222. doi: 10.1089/crispr.2020.0141
Lamsfus-Calle A*, Daniel-Moreno A*, Antony JS, Epting T, Heumos L, Baskaran P, Admar J, Casadei N, Latifi N, Siegmund D, Kormann M, Handgretinger R, Mezger M (2020) Comparative targeting analysis of KLF1, BCL11A and HBG1/2 in CD34+ HSPCs by CRISPR/Cas9 for the induction of fetal hemoglobin. Nature Scientific Reports 10(1):10133. doi: 10.1038/s41598-020-66309-x.
Lamsfus-Calle A*, Daniel-Moreno A*, Ureña-Bailén G, Raju J, Antony J, Handgretinger R, Mezger M (2019) Hematopoietic Stem Cell Gene Therapy: The optimal use of Lentivirus and Gene Editing Approaches. Blood Reviews 15:100641. doi: 10.1016/j.blre.2019.100641
Hünefeld C*, Mezger M*, Müller-Hermelink E, Müller I, Amagai M, Handgretinger R, Röcken M (2018) Bone Marrow-Derived Stem Cells Migrate into Intra-epidermal Skin Defects of a Desmoglein-3 knockout Mouse Model but Preserve their Mesodermal Differentiation. Journal of Investigative Dermatology 138(5): 1157-1165
Oevermann L*, Michaelis S*, Mezger M*, Lang P, Toporski J, Bertaina A, Zecca M, Moretta L, Locatelli F*, Handgretinger R* (2014) KIR B haplotype donors confer a reduced risk of relapse after haploidentical transplantation in children with acute lymphoblastic leukemia. Blood 124: 2744-2747
Mezger M, Steffens M, Beyer M, Manger C, Eberle J, Toliat MR, Wienker TF, Ljungman P, Hebart H, Dornbusch HJ, Einsele H, Loeffler J (2008) Polymorphisms in the chemokine (C-X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 expression in monocyte-derived dendritic cells. Blood 111: 534-536