Virus-Host Interactions
Prof. Dr. Dirk Grimm
We specialize in advancing human gene therapy through innovative gene delivery methods using parvoviruses like AAV and bocavirus.
We work on gene therapy with AAV i.e., non-pathogenic Adeno-associated viruses, which are the most promising and most versatile viral vector for therapeutic gene transfer and which we engineer using a large portfolio of technologies such as DNA shuffling, peptide display, DNA/RNA barcoding, high-throughput in vivo screening in small or large animals, single-cell (sc)RNA sequencing and targeting a variety of diseases including infection with SARS-CoV-2 (Covid-19), human immunodeficiency virus (HIV; AIDS), hepatitis viruses (HB/D/EV), or disorders of the muscle, liver, CNS, eye at our various locations in Heidelberg
Research Strategy
Human gene therapy, i.e., the efficient and specific correction of diseases at the DNA/ RNA level by gene addition, repression or repair, is one of the most powerful and most versatile technologies in modern biomedicine. To foster its accessibility and application for patients’ benefits, we focus on the engineering and in vivo validation of novel gene delivery vehicles (vectors) derived from parvoviruses, including apathogenic Adeno-associated virus (AAV) and bocavirus. To this end, we develop and harness state-of-the-art viral vector technologies comprising molecular evolution of AAV capsid proteins, DNA/RNA barcoding of capsid or promoter libraries, high-throughput in vivo screens from the cell to the organ level, as well as bioinformatic and machine learning approaches for rational vector design. Clinically relevant targets include a wide assortment of infectious pathogens such as SARS-CoV-2, HIV or hepatitis viruses B-E, as well as monogenic disorders such as Duchenne muscular dystrophy or brain diseases.
While work from the past 15 years conducted by us in BioQuant and other teams world-wide has demonstrated the power and potential of top-down AAV engineering and screening approaches, it has likewise become evident that novel stratagems are required to truly fulfill the promise of human gene therapy. In particular, we aim to improve the specificity and thus safety of viral vector-mediated gene transfer, by combining our portfolio of barcoding technologies with the latest single-cell/-nuclei and spatial transcriptomics platforms to achieve an unprecedented three-dimensional resolution at the cellular level. Concurrently, by expanding our knowledge on natural AAV evolution through a combination of experimental and bioinformatic screenings for new AAV variants, and by harnessing the results for AI-based dissection of AAV biology and in silico prediction of designer viruses, we aim to close a major gap in translational gene therapy research and to facilitate personalized biomedicine.
Prof. Dr. Dirk Grimm
- +49 (0)6221 54-51331
- dirk.grimm@bioquant.uni-heidelberg.de
- Room 445
- Find out more information here
Selected Publications
Methane formation driven by reactive oxygen species across all living organisms
Leonard Ernst, Benedikt Steinfeld, Uladzimir Barayeu, Thomas Klintzsch, Markus Kurth, Dirk Grimm, Tobias P. Dick, Johannes G. Rebelein, Ilka B. Bischofs & Frank Keppler
Nature volume 603, pages 482-487 (2022)
Ex vivo and in vivo suppression of SARS-CoV-2 with combinatorial AAV/RNAi expression vectors
Jonas Becker, Megan Lynn Stanifer, Sarah Rebecca Leist, Bettina Stolp, Olena Maiakovska, Ande West, Ellen Wiedtke, Kathleen Börner, Ali Ghanem, Ina Ambiel, Longping Victor Tse, Oliver Till Fackler, Ralph Steven Baric, Steeve Boulant, Dirk Grimm
Mol Ther.2022 May 4;30(5):2005-2023
Jonas Weinmann, Sabrina Weis, Josefine Sippel, Warut Tulalamba, Anca Remes, Jihad El Andari, Anne-Kathrin Herrmann, Quang H. Pham, Christopher Borowski, Susanne Hille, Tanja Schönberger, Norbert Frey, Martin Lenter, Thierry VandenDriessche, Oliver J. Müller, Marinee K. Chuah, Thorsten Lamla & Dirk Grimm
Nature Communications volume 11, Article number: 5432 (2020)