Gene editing-based technologies and therapies in cancer and infectious diseases

Our main interest is to develop advanced gene editing technologies and adapt them for different lab-related and therapeutic applications. The main goal is to establish innovative therapeutic approaches against cancer either by using functional delivery of CRISPR/Cas9 machinery through engineered extracellular vesicles, or by modulating human lymphocyte activation and effector functions to improve lymphocyte-based immunotherapy.
We also use state-of-the-art gene editing technologies in human primary cells to investigate the key cellular and molecular mechanisms involved in host-pathogen interactions in various infectious disease models, expanding the knowledge of these processes as well as identifying new potential therapeutic targets.

Major research project:

“Engineered extracellular vesicles for personalized leukemia therapy”.
Cancer is one of the leading causes of death worldwide. Surgery, chemotherapy, and radiotherapy are still the most common treatment strategies. Immunotherapy is becoming another important approach to treating some cancers, mainly in combination with other treatments. Our group is currently developing a therapeutic approach based on extracellular vesicles to deliver drugs or effector proteins to the target cancer cells thus creating a universal yet customizable therapeutic strategy that can be adapted for different applications in a patient-specific manner.

Projects

  • Engineered extracellular vesicles for personalized leukemia therapy – funded by AIRC (My First AIRC Grant)
  • Lymphocyte engineering using CRISPR/Cas9-based knock-out and knock-in approaches to improve immunotherapy – in collaboration with the Lanzavecchia group
  • Functional genomic to investigate infectious diseases (EBV, HIV-1, SARS-CoV2) – in collaboration with the De Francesco and Manganaro groups

 

Keywords:

Leukemia, CRISPR/Cas9, Extracellular vesicles, viral infection.

Team

Nome / NameRuolo / RoleEmail
Abeer MahfoudMaster Studentmahfoud@ingm.org
Alice RandonResearch Assistantrandon@ingm.org

Publications

  • Autoantibody-enhanced, CD32-driven trogocytosis creates functional plasticity of immune cells and is hijacked by HIV-1 to infect resting CD4 T cells.
    Albanese M, Chen HR, Gapp M, Muenchhoff M, Yang H-H, Peterhoff D, Hoffmann K, Xiao Q, Ruhle A, Ambiel I, Schneider S, Mejías-Pérez E, Stern M, Wratil PR, Hofmann K, Amann L, Jocham L, Fuchs T, Ulivi AF, Besson-Girard S, Weidlich S, Schneider J, Spinner CD, Sutter K, Dittmer U, Humpe A, Baumeister P, Wieser A, Rothenfusser S, Bogner J, Roider J, Knolle P, Hengel H, Wagner R, Laketa V, Fackler OT, Keppler OT.
    Cell Reports Medicine 2024. In press
  • Strategies of Epstein-Barr virus to evade innate antiviral immunity of its human host.
    Albanese M, Tagawa T, and Hammerschmidt W.
    Frontiers in Microbiology 2022. doi:10.3389/fmicb.2022.955603
  • Rapid, efficient and activation-neutral gene editing of polyclonal primary human resting CD4+ T cells allows complex
    functional analyses.
    Albanese M#, Ruhle A, Mittermaier J, Mejías-Pérez E, Gapp M, Linder A, Schmacke NA, Hofmann K, Hennrich AA, Levy DN, Humpe A, Conzelmann KK, Hornung V, Fackler OT, Keppler OT#.
    Nature Methods 2022. doi: 10.1038/s41592-021-01328-8.
  • Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern.
    Wratil PR, Stern M, Priller A, Willmann A, Almanzar G, Vogel E, Feuerherd M, Cheng CC, Yazici S, Christa C, Jeske S, Lupoli G, Vogt T, Albanese M, Mejías-Pérez E, Bauernfried S, Graf N, Mijocevic H, Vu M, Tinnefeld K, Wettengel J, Hoffmann D, Muenchhoff M, Daechert C, Mairhofer H, Krebs S, Fingerle V, Graf A, Steininger P, Blum H, Hornung V, Liebl B, Überla K, Prelog M, Knolle P, Keppler OT, Protzer U.
    Nature Medicine 2022. doi: 10.1038/s41591-022-01715-4.
  • LFA1 and ICAM1 are critical for fusion and spread of murine leukemia virus in vivo.
    Engels M, Falk L, Albanese M, Keppler OT, Sewald X.
    Cell Reports 2022. doi:10.1016/j.celrep.2021.110279.
  • MicroRNAs are minor constituents of extracellular vesicles that are rarely delivered to target cells.
    Albanese M#, Chen YA, Hüls C, Gärtner K, Tagawa T, Mejias-Perez E, Keppler OT, Göbel C, Zeidler R, Shein M, Schütz AK, Hammerschmidt W#.
    PLoS Genetics 2021. doi: 10.1371/journal.pgen.1009951.
  • Highly efficient CRISPR-Cas9-mediated gene knockout in primary human B cells for functional genetic studies of Epstein-Barr virus infection.
    Akidil E, Albanese M, Buschle A, Ruhle A, Keppler OT, Hammerschmidt W.
    PLoS Pathog. 2021. doi: 10.1371/journal.ppat.1009117.
  • microRNAs of Epstein-Barr virus control innate and adaptive anti-viral immunity.
    Albanese M, Tagawa T, Buschle A and Hammerschmidt W.
    Journal of Virology 2017. doi: 10.1128/JVI.01667-16.
  • Epstein-Barr virus miRNAs mediate escape from CD8+ T cell recognition.
    Albanese M, Tagawa T, Bouvet M, Lutter D, Hoser J, Hastreiter M, Hayes M, Sugden B, Martin LK, Moosmann A, and Hammerschmidt W.
    Proceedings of the National Academy of Sciences USA 2016. doi:10.1073/pnas.1605884113.
  • Epstein-Barr Viral miRNAs inhibit antiviral CD4+ T cell responses targeting IL-12 and antigen presentation.
    Tagawa T, Albanese M, Bouvet M, Mautner J, Heissmeyer V., Zielinski C., Lutter D., Hoser J., Hastreiter M., Hayes M., Sugden B., Martin L.K., Moosmann A., and Hammerschmidt W.
    The Journal of Experimental Medicine 2016. doi: 10.1084/jem.20160248.

 

# co-corresponding author

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