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ESGCT 29th Annual Congress In collaboration with BSGCT, Edinburgh, UK October 11–14, 2022 - Abstracts Gene therapy is an effective treatment for genetic disorders by delivery of therapeutic genes to tissues, such as the liver. Gene transfer can use viral vectors such as adeno‐associated virus, where, once delivered to the nucleus can remain episomally or integrated into the host DNA. Recently, adeno‐associated viruses have shown to been found associated with hepatocellular carcinoma in mice, which is likely due to vector effects on gene(s) local to the site of integration. Models to determine potential gene therapy vector genotoxicity have been developed, however, these often use animals, cells of murine origin or immortal cells that may be oversensitive in predicting human genotoxic risk. To circumvent this, we developed a human based model using induced pluripotent stem cells and their hepatocyte‐like cell derivatives. Cells were profiled for markers of pluripotency and terminal differentiation, respectively, then transcriptomically demonstrating hepatocyte‐like cell expression aligning with primary human hepatocytes. Cells were infected with adeno‐associated vectors using the strong Chicken β‐actin (CB7) or weak Apo‐lipoprotein (ApoE) promoters to drive GFP expression and investigated for integration by EPTS/LM‐PCR that showed twice as many insertions in cancer genes by the ApoE vector than the CB7 vector. RNASeq profiling of infected cells also identified cancer gene fusion transcripts between adeno‐associated virus and host cells and analysis of methylation changes in the infected cells showed differences in global methylation profiles by each vector. We present this model as useful to identify and measure the genotoxic potential of these vectors on the host.

Poster-Abstract

The year 2021 was still overshadowed by waves of the COVID-19 pandemic, although the arrival of efficient vaccinations together with the experience of the preceding year gave us a certain routine in handling the situation. By now the execution of meetings in an online mode using zoom and similar video conference systems has been recognized as actually being useful in certain situations, e.g. instead of flying across Europe to attend a three-hours meeting, but also to be able to attend seminars of distinguished scientists which otherwise would not be easily accessible. The scientific productivity of the institute has remained on a very high level, counting 190 publications with an unprecedented average impact factor of 8.0. Six outstanding and representative publications are reprinted in this Annual Report. 16 new third-party projects were granted, among them 7 DFG projects, but very remarkably also an EU funded project on nonlinear magnons for reservoir computing with industrial participation of Infineon Technologies Dresden and GlobalFoundries Dresden coordinated by Kathrin Schultheiß of our Institute. The scientific success was also reflected in two HZDR prizes awarded to the members of the Institute: Dr. Katrin Schultheiß received the HZDR Forschungspreis for her work on “Nonlinear magnonics as basis for a spin based neuromorphic computing architecture”, and Dr. Toni Hache was awarded the Doktorandenpreis for his thesis entitled “Frequency control of auto-oscillations of the magnetization in spin Hall nano-oscillators”. Our highly successful theoretician Dr. Arkady Krasheninnikov was quoted as Highly Cited Researcher 2021 by Clarivate. The new 1-MV facility for accelerator mass spectrometry (AMS) has been ordered from NEC (National Electrostatics Corporation). Design of a dedicated building to house the accelerator, the SIMS and including additional chemistry laboratories for enhanced sample preparation capabilities has started and construction is planned to be finished by mid 2023, when the majority of the AMS components are scheduled for delivery. In the course of developing a strategy for the HZDR - HZDR 2030+ Moving Research to the NEXT Level for the NEXT Gens - six research focus areas for our institute were identified. Concerning personalia, it should be mentioned that the long-time head of the spectroscopy department PD Dr. Harald Schneider went into retirement. His successor is Dr. Stephan Winnerl, who has been a key scientist in this department already for two decades. In addition, PD Dr. Sebastian Fähler was hired in the magnetism department who transferred several third-party projects with the associated PhD students to the Institute and strengthens our ties to the High Magnetic Field Laboratory, but also to the Institute of Fluid Dynamics. Finally, we would like to cordially thank all partners, friends, and organizations who supported our progress in 2021. First and foremost we thank the Executive Board of the Helmholtz-Zentrum Dresden-Rossendorf, the Minister of Science and Arts of the Free State of Saxony, and the Ministers of Education and Research, and of Economic Affairs and Climate Action of the Federal Government of Germany. Many partners from universities, industry and research institutes all around the world contributed essentially, and play a crucial role for the further development of the institute. Last but not least, the directors would like to thank all members of our institute for their efforts in these very special times and excellent contributions in 2021.

Poster-Abstract