Article
Multidisciplinary Sciences
Tobias P. Woerner, Antonette Bennett, Sana Habka, Joost Snijder, Olga Friese, Thomas Powers, Mavis Agbandje-McKenna, Albert J. R. Heck
Summary: Recent research on Adeno-associated viruses (AAVs) using high-resolution native mass spectrometry has revealed that the capsids of different AAV serotypes assemble stochastically, leading to a highly heterogeneous population of capsids with varying compositions. Even the most abundant VP stoichiometry represents only a small percentage of the total AAV population. The systematic scoring of simulations against experimental native MS data offers a sensitive new method to characterize these therapeutically important heterogeneous capsids.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Anh K. Lam, Dylan Frabutt, Lei Li, Weidong Xiao
Summary: This review summarizes recent advances in AAV capsid chemical modification and discusses future directions to enhance its therapeutic use in gene therapy.
HUMAN GENE THERAPY
(2021)
Article
Virology
Jane Hsi, Mario Mietzsch, Paul Chipman, Sandra Afione, Allison Zeher, Rick Huang, John Chiorini, Robert Mckenna
Summary: The avian adeno-associated virus (AAAV) has low sequence identities to other AAV serotypes and utilizes galactose for cell attachment. However, approximately 30% of human sera tested were able to neutralize the transduction effect of AAAV, possibly due to the presence of conserved epitopes in the capsid's fivefold region. These findings are important for the further development of AAV vectors in gene therapy.
JOURNAL OF VIROLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Servio H. Ramirez, Jonathan F. Hale, Siobhan McCarthy, Christian L. Cardenas, Kalpani N. Udeni Galpayage Dona, Killian S. Hanlon, Eloise Hudry, Demitri De La Cruz, Carrie Ng, Sabyasachi Das, Diane M. Nguyen, Josette Nammour, Rachel E. Bennett, Allison M. Andrews, Patricia L. Musolino, Casey A. Maguire
Summary: Neurodegeneration and cerebrovascular disease share microvascular dysfunction, which can be remedied by selective transgene delivery. A study characterized an engineered adeno-associated virus (AAV) capsid that effectively targets cerebral vascular pericytes and smooth muscle cells (SMCs). The identified capsid, AAV-PR, showed high transduction of brain vasculature, including pericytes and SMCs, offering the possibility of genetically modulating these cell types in the context of neurodegeneration and other neurological diseases.
HUMAN GENE THERAPY
(2023)
Article
Chemistry, Analytical
Lisa Strasser, Tomos E. Morgan, Felipe Guapo, Florian Fussl, Daniel Forsey, Ian Anderson, Jonathan Bones
Summary: This study presents a native mass spectrometry-based approach for assessing the ratio of empty to full AAV capsids in a rapid and accurate manner, without the need for extensive sample preparation. The results demonstrate good correlation with more traditional analysis strategies, indicating the potential of native mass spectrometry for viral particle characterization.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Mathilde Briday, Francois Halle, Lauriane Lecoq, Sylvie Radix, Juliette Martin, Roland Montserret, Marie Dujardin, Marie-Laure Fogeron, Michael Nassal, Beat H. Meier, Thierry Lomberget, Anja Bockmann
Summary: Hepatitis B virus (HBV) is a significant human pathogen and its capsid-forming core protein (Cp) plays a key role in envelopment. Recent studies have found that Triton X-100, a detergent used in Cp purification, strongly binds to the hydrophobic pocket of Cp. The aromatic moiety is crucial for binding, while the aliphatic chain affects binding affinity. Moreover, the hydrophilic tail shows high tolerance to changes in length and type.
Article
Biotechnology & Applied Microbiology
Amy Henrickson, Xiaozhe Ding, Austin G. Seal, Zhe Qu, Lauren Tomlinson, John Forsey, Viviana Gradinaru, Kazuhiro Oka, Borries Demeler
Summary: This study presents guidelines for experimental design of multi-wavelength analytical ultracentrifugation (MW-AUC) and compares its results with other methods. The results demonstrate that MW-AUC provides more accurate characterization and quantification of adeno-associated viruses, and identifies contaminants.
Review
Biochemistry & Molecular Biology
Florian Kreppel, Claudia Hagedorn
Summary: Adenovirus-based gene transfer vectors are widely used in gene therapy clinical trials and as genetic vaccine candidates during the SARS-CoV-2 pandemic. Immune responses induced by these vectors can be modulated through extensive genomic and chemical capsid modifications, with potential synergistic effects that require further investigation in preclinical studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Jared S. Bee, Yu Zhang (Zoe), Sheyla Finkner, Kristin O'Berry, Akanksha Kaushal, Megan Kuhn Phillippi, Roberto A. DePaz, Keith Webber, Tristan Marshall
Summary: Gene therapies using adeno-associated virus (AAV) vectors have great potential. This study investigates the mechanisms of AAV capsid rupture during freeze-thaw (F/T) cycles and proposes three formulation mitigation approaches to stabilize AAV.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Zachary C. Elmore, L. Patrick Havlik, Daniel K. Oh, Leif Anderson, George Daaboul, Garth W. Devlin, Heather A. Vincent, Aravind Asokan
Summary: The membrane-associated accessory protein (MAAP) is identified as a novel viral egress factor that promotes the secretion of AAV serotypes. MAAP contains a cationic amphipathic domain critical for AAV secretion. Restoring MAAP expression can rescue the secretion defect in various AAV serotypes with mutated start sites.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yasunaga Shiraishi, Takeshi Adachi, Jose M. Cacicedo, Yasuo Ido
Summary: The study aimed to develop a simple and high-quality method for obtaining enough lung-targeted rAAV. The authors achieved this by introducing mutations, optimizing culture conditions, and improving the purification method, resulting in stable and lung-targeted rAAVs.
Article
Biochemistry & Molecular Biology
Zhuoying Feng, Fanghang Zhou, Miaomiao Tan, Tingting Wang, Ying Chen, Wenwen Xu, Bin Li, Xin Wang, Xin Deng, Ming-Liang He
Summary: HSV-1 infection enhances the expression of m6A modification-related genes to facilitate viral replication, while inhibiting m6A modification reduces viral replication and reproduction.
Article
Virology
Sean M. Crosson, Antonette Bennett, Diego Fajardo, James J. Peterson, Hangning Zhang, Wei Li, Matthew T. Leahy, Colin K. Jennings, Ryan F. Boyd, Sanford L. Boye, Mavis Agbandje-McKenna, Shannon E. Boye
Summary: Rationally designed AAV2-based capsid variants with specific hydrophilic and hydrophobic amino acid mutations can significantly enhance retinal transduction, especially when considering the impact of these mutations on HSPG binding and vector tropism in a clinically relevant animal model.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Megane K. Aebischer, Thomas Bouvarel, Emmalyn Barrozo, Dominik Kochardt, Carsten Elger, Markus Haindl, Raphael Ruppert, Davy Guillarme, Valentina D'Atri
Summary: The purity of recombinant adeno-associated virus (rAAV), a gene therapy product, is important for its quality. Various electrophoretic and chromatographic methods were compared for characterizing the three viral proteins (VPs) in this study. Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) is considered the reference method but has limitations in post-translational modification characterization and species identification. Reversed phase liquid chromatography (RPLC) and hydrophilic interaction chromatography (HILIC) showed compatibility with mass spectrometry (MS) and sensitivity in detecting capsid protein variants, while hydrophobic interaction chromatography (HIC) performed poorly.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Ekaterina M. Shitik, Igor K. Shalik, Dmitry V. Yudkin
Summary: Recombinant adeno-associated virus (rAAV) is a leading platform for gene delivery, but improvements are needed to enhance vector performance. This review focuses on modifying ITRs, transgene cassettes, and Rep proteins as ways to improve rAAV vectors and increase transduction efficiency.
FRONTIERS IN MEDICINE
(2023)
Article
Hematology
Till Braun, Markus Glass, Linus Wahnschaffe, Moritz Otte, Petra Mayer, Marek Franitza, Janine Altmuller, Michael Hallek, Stefan Huttelmaier, Alexandra Schrader, Marco Herling
Summary: T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic mature T-cell malignancy. A better understanding of T-PLL's pathogenesis is desirable and in this study, the researchers identified miR expression profiles and regulatory networks associated with cell survival signaling and DNA damage response pathways in T-PLL. They found that miR-141 and the miR-200c-cluster can separate T-PLL cases into two major subgroups, and increased expression of miR-223-3p as well as reduced expression of miR-21 and the miR-29 cluster are associated with more activated T-cell phenotypes and more aggressive disease presentations.
Article
Hematology
Henriette Huber, Simone Edenhofer, Julia von Tresckow, Sandra Robrecht, Can Zhang, Eugen Tausch, Christof Schneider, Johannes Bloehdorn, Moritz Fuerstenau, Peter Dreger, Matthias Ritgen, Thomas Illmer, Anna L. Illert, Jan Duerig, Sebastian Boettcher, Carsten U. Niemann, Michael Kneba, Anna-Maria Fink, Kirsten Fischer, Hartmut Doehner, Michael Hallek, Barbara Eichhorst, Stephan Stilgenbauer
Summary: Despite advances in targeted therapies, patients with high-risk chronic lymphocytic leukemia (CLL) still have inferior outcomes compared to others. The CLL2-GIVe treatment regimen, combining multiple agents, has shown good efficacy and manageable safety as a first-line treatment for high-risk CLL.
Article
Hematology
Christian Brieghel, Veerle Galle, Rudi Agius, Caspar Da Cunha-Bang, Michael A. Andersen, Philip Vlummens, Mattias Mattsson, Richard Rosenquist, Karin E. Smedby, Carmen D. Herling, Jasmin Bahlo, Michael Hallek, Jens D. Lundgren, Fritz Offner, Carsten U. Niemann
Summary: A prognostic index was developed and validated to identify newly diagnosed CLL patients without need of treatment, allowing for better management and follow-up.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2022)
Article
Oncology
Lisa Rusyn, Sebastian Reinartz, Anastasia Nikiforov, Nelly Mikhael, Alexander vom Stein, Viktoria Kohlhas, Johannes Bloehdorn, Stephan Stilgenbauer, Philipp Lohneis, Reinhard Buettner, Sandra Robrecht, Kirsten Fischer, Christian Pallasch, Michael Hallek, Phuong-Hien Nguyen, Tamina Seeger-Nukpezah
Summary: The scaffold protein NEDD9 is frequently upregulated and hyperphosphorylated in cancers, and its overexpression is associated with poor clinical outcome. In this study, the researchers found that deleting the Nedd9 gene in chronic lymphocytic leukemia (CLL) mouse models delayed CLL development, reduced disease burden, and improved survival. NEDD9 was found to be essential for efficient CLL cell homing, chemotaxis, migration, and adhesion. These findings suggest a functional role of NEDD9 in CLL pathogenesis, specifically in adhesion, migration, and homing defects.
Editorial Material
Oncology
Petra Langerbeins, Barbara Eichhorst, Michael Hallek
Article
Oncology
Theophilos Tzaridis, Johannes Weller, Daniel Bachurski, Farhad Shakeri, Christina Schaub, Peter Hau, Andreas Buness, Uwe Schlegel, Joachim-Peter Steinbach, Clemens Seidel, Roland Goldbrunner, Niklas Schaefer, Robert J. Wechsler-Reya, Michael Hallek, Bjoern Scheffler, Martin Glas, Lothar Haeberle, Ulrich Herrlinger, Christoph Coch, Katrin S. Reiners, Gunther Hartmann
Summary: Evaluation of serum-derived extracellular vesicles (EVs) from glioblastoma patients reveals that the upregulation of CD29, CD44, CD81, C1QA, and histone H3 in serum EVs correlates with tumor progression, suggesting their potential as biomarkers.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Volker Arndt, Daniela Doege, Stefan Froehling, Peter Albers, Hana Alguel, Ralf Bargou, Carsten Bokemeyer, Martin Bornhaeuser, Christian H. Brandts, Peter Brossart, Sara Yvonne Brucker, Tim H. Bruemmendorf, Hartmut Doehner, Norbert Gattermann, Michael Hallek, Volker Heinemann, Ulrich Keilholz, Thomas Kindler, Cornelia von Levetzow, Florian Lordick, Ulf Peter Neumann, Christoph Peters, Dirk Schadendorf, Stephan Stilgenbauer, Thomas Zander, Daniel Zips, Delia Braun, Thomas Seufferlein, Gerd Nettekoven, Michael Baumann
Summary: The capacities of German Comprehensive Cancer Centers (CCCs) in various aspects of oncology care were significantly affected during the first 2 years of the COVID-19 pandemic. Follow-up, psycho-oncologic care, and tumor surgery were particularly impacted, along with other areas of multidisciplinary oncological care. This study highlights the importance of developing strategies to prevent similar limitations in the future.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Hematology
Jorge Garcia Borrega, Boris Boell, Matthias Kochanek, Jan-Hendrik Naendrup, Florian Simon, Noelle Sieg, Michael Hallek, Peter Borchmann, Udo Holtick, Alexander Shimabukuro-Vornhagen, Dennis A. Eichenauer, Jan-Michel Heger
Summary: A retrospective analysis was conducted on patients admitted to the intensive care unit (ICU) during hospitalization for high-dose chemotherapy and autologous stem cell transplantation (ASCT). The study found that the overall outcome was favorable for these patients.
ANNALS OF HEMATOLOGY
(2023)
Meeting Abstract
Hematology
Nadine Kutsch, Anna Maria Fink, Anno Federhen, Adam Giza, Sandra Robrecht, Janina Stumpf, Andrea Stoltefuss, Ursula Vehling-Kaiser, Michael Koenigsmann, Eugen Tausch, Christof Schneider, Stephan Stilgenbauer, Thomas Illmer, Rudolf Schlag, Steffen Doerfel, Tobias Gaska, Michael G. Kiehl, Kirsten Fischer, Barbara Eichhorst, Michael Hallek
Meeting Abstract
Hematology
Eugen Tausch, Christof Schneider, Moritz Furstenau, Sandra Robrecht, Deyan Yordanov Yosifov, Daniel Mertens, Michael Gregor, Patrick Thornton, Philipp B. Staber, Tamar Tadmor, Mark-David Levin, Caspar Da Cunha-Bang, Christian Bjorn Poulsen, Thomas Illmer, Bjoern Schoettker, Ann Janssens, Ilse Christiansen, Thomas Noesslinger, Michael Baumann, Clemens-Martin Wendtner, Eric Eldering, Karl-Anton Kreuzer, Matthias Ritgen, Anna-Maria Fink, Kirsten Fischer, Arnon P. Kater, Carsten Utoft Niemann, Michael Hallek, Barbara Eichhorst, Stephan Stilgenbauer
Article
Oncology
Nadine Kutsch, Emily Eva Holmes, Sandra Robrecht, Gudrun Schueler, Ursula Vehling-Kaiser, Thomas Decker, Sigrun Mueller-Hagen, Karin Heinisch, Sebastian Boettcher, Matthias Ritgen, Karl-Anton Kreuzer, Stephan Stilgenbauer, Anna Maria Fink, Kirsten Fischer, Barbara Eichhorst, Michael Hallek, Clemens-Martin Wendtner
LEUKEMIA & LYMPHOMA
(2023)
Article
Oncology
Ruth Fluemann, Julia Hansen, Benedikt W. Pelzer, Pascal Nieper, Tim Lohmann, Ilmars Kisis, Tobias Riet, Viktoria Kohlhas, Phuong-Hien Nguyen, Martin Peifer, Nima Abedpour, Graziella Bosco, Roman K. Thomas, Moritz Kochanek, Jacqueline Knufer, Lorenz Jonigkeit, Filippo Beleggia, Alessandra Holzem, Reinhard Buttner, Philipp Lohneis, Jorn Meinel, Monika Ortmann, Thorsten Persigehl, Michael Hallek, Dinis Pedro Calado, Markus Chmielewski, Sebastian Klein, Joachim R. Goethert, Bjoern Chapuy, Branko Zevnik, F. Thomas Wunderlich, Bastian von Tresckow, Ron D. Jachimowicz, Ari M. Melnick, Hans Christian Reinhardt, Gero Knittel
Summary: Genomic profiling identified 5 subtypes of DLBCL, including the MCD/C5 cluster with MYD88, BCL2, PRDM1, and/or SPIB aberrations. Mouse models with B cell-specific Prdm1 or Spib aberrations were generated, showing molecular features of prememory and light-zone B cells. Combined BTK/BCL2 inhibition exhibited therapeutic activity in both mouse models and relapsed/refractory DLBCL patients.
BLOOD CANCER DISCOVERY
(2023)
Article
Medicine, General & Internal
L. Tometten, J. J. Malin, E. Pracht, P. J. Broeckelmann, C. Horn, R. Sprute, C. A. Langhorst, M. Hallek, G. Faetkenheuer, J. Rybniker
Summary: Immunodeficient patients with chronic and recurrent SARS-CoV-2 infections pose a significant health threat and present a major challenge in terms of treatment during the ongoing pandemic. Limited therapeutic options and emerging virus variants with immune escape mechanisms further complicate the medical care of these patients.
Meeting Abstract
Oncology
Dina Sahi, David Hoier, Petra Stamm, Carolin Gross-Ophoff-Mueller, Michael Hallek, Axel Heidenreich
ONCOLOGY RESEARCH AND TREATMENT
(2022)
Article
Medicine, General & Internal
Max Augustin, M. Hallek, S. Nitschmann