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Adresse: Otfried-Müller-Straße 10
72076 Tübingen


Gründungs-Direktorin

frontend.sr-only_#{element.icon}: 07071 29-82168
Prof. Julia Skokowa


frontend.sr-only_#{element.icon}: julia.skokowa@med.uni-tuebingen.de


Wissenschaftliche Koordinatorin

frontend.sr-only_#{element.icon}: 07071 29-86013
Dr. Olga Klimenkova


frontend.sr-only_#{element.icon}: Olga.Klimenkova@med.uni-tuebingen.de


AG Mezger

Portraitfoto

Dr. med. Dr. rer. nat. Dipl. Biol. Markus Mezger

Paediatrics I - General Paediatrics, Haematology and Oncology

Personenprofil: More about the person

Pediatric Cell and Gene Therapy

Our team is working in pediatric hematology and oncology in the field of hematopoietic stem cell transplantation. By utilizing various cell and gene therapy approaches, we aim to develop novel gene therapies for β- hemoglobinopathies (β-thalassemia, sickle cell disease), cancer immunotherapy, and rare diseases including metachromatic leukodystrophy, as well as immunodeficiencies. Our technologies include lentiviral and Adeno-associated virus gene transfer, mRNA therapeutics, adoptive immune cell therapy, genome editing and gene correction using CRISPR / Cas9 system. For more detailed information, see our homepage at UKT (link below).


List of GRT projects

  • Gene correction of human b-thalassemic hematopoietic stem cells using CRISPR/Cas9 system
  • Hematopoietic stem cell gene therapy with Cas9 mRNA and AAV6 vector in metachromatic leukodystrophy
  • Improvement of CAR T-cell and CAR NK-cell anti-leukemic effector functions using CRISPR/Cas9 technology
  • Antibody optimization in CHO-S cells using CRISPR/Cas9 gene editing for enhanced anti-tumor activity
  • Using CRISPR/Cas9 system and prime editing for the treatment of IL2RG immunodeficiency
  • Improvement of cell fitness after CRISPR/Cas9 electroporation by anti-ROS compounds


GRT expertise

Hematology, oncology, hematopoietic stem cell transplantation, b-hemoglobinopathies, metachromatic leukodystrophy, ex vivo gene editing


Main GRT methods applied in the lab

CRISPR/Cas system, AAV based gene correction, lentiviral gene therapy, mRNA production and delivery, transfection of primary hematopoietic stem cells, CAR T-cells, CAR NK cells, CliniMACS Prodigy, on-/off target analysis, prime editing, digital droplet PCR

Publications

  • 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 (2021) A mutation-agnostic hematopoietic stem cell gene therapy for metachromatic leukodystrophy. The CRISPR Journal 5(1):66-79doi: 10.1089/crispr.2021.0075. 
  • Grote S, Ureña-Bailén G, Chun-Ho Chan K, Baden C, Mezger M, Handgretinger R, Schleicher S (2021) In vitro evaluation of CD276-CAR NK-92 functionality, migration and invasion potential in the presence of immune inhibitory factors of the tumor microenvironment. Cells 10(5), 1020. doi.org/10.3390/cells10051020
  • 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. 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 (2020) Hematopoietic Stem Cell Gene Therapy: The optimal use of Lentivirus and Gene Editing Approaches. Blood Reviews 40:100641. doi: 10.1016/j.blre.2019.100641.