Gene editing-based technologies and therapies in cancer and infectious diseases
Our main interest is to develop and adapt advanced gene editing technologies for various laboratory and therapeutic applications. The main goal is to establish innovative therapeutic approaches against different diseases, either by functional delivery of gene editing machineries through engineered extracellular vesicles, or by modulation of human lymphocyte activation and effector functions to improve lymphocyte-based immunotherapy.
Cancer is a leading cause of death worldwide. Surgery, chemotherapy and radiotherapy are still the most common treatment strategies. However, due to the heterogeneity of cancers and patients, there is no single effective therapy. Tailoring an individualized combination of treatments to each cancer patient is the most promising option for eradicating cancer and preventing recurrence.
Infectious diseases also cause millions of deaths each year. Once infected, most viruses are eliminated by our immune system. However, some can persist in the human host for long periods of time, establishing what is commonly referred to as viral latency. These viruses are responsible for a variety of diseases that can be chronic and require lifelong treatment, representing a significant socioeconomic burden to the global population.
Our research focuses on the development of novel therapeutic strategies that will revolutionize current cancer and antiviral treatments. Our group is currently developing an extracellular vesicle-based therapeutic approach to deliver drugs or effector proteins to the target cells of interest. In addition, we are using cutting-edge 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 to advance our understanding of these processes and identify new potential therapeutic targets.
Our goal is to develop therapies tailored to each patient, harnessing the potential of personalized medicine. In this way, we aim to significantly improve patients’ quality of life and reduce the impact of these devastating diseases.
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
- DELIEV – DELIvery of antiviral Extracellular Vesicles to target chronic infections (funded by MUR – Fondo Italiano per la Scienza 2)
- 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
- NEURO-Tr1: Role of cytotoxic T-cell subsets in neurodegenerative diseases (PNRR, MNESYS, Spoke 7, Bando a cascata) – in collaboration with the Geginat 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 / Name | Ruolo / Role | |
|---|---|---|
| Abeer Mahfoud | Master Student | mahfoud@ingm.org |
| Alice Randon | Research Assistant | randon@ingm.org |
| Silvia Fiori | PostDoc | fiori@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
INGM RESEARCH IS SUPPORTED BY
