Article
Virology
Nora A. Bahlmann, Raphael L. Tsoukas, Sebastian Erkens, Hongjie Wang, Franziska Jonsson, Malik Aydin, Ella A. Naumova, Andre Lieber, Anja Ehrhardt, Wenli Zhang
Summary: Carcinomas exhibit an upregulation of intercellular junctions that hinder immune response and drug therapy. The interaction between human adenovirus type 3 (Ad3) and Desmoglein 2 (DSG2) leads to a shedding of the binding domain and opening of tight junctions. The JO-4 protein, derived from Ad3, has been shown to enhance antibody therapy and chemotherapy effects. However, our study found that introducing the JO4 mutation to adenoviral vectors did not result in increased transduction in DSG2-high cell lines and weakened effects in DSG2-low cell lines. In fact, the JO4 vectors showed resistance in DSG2-negative cell lines possibly due to the negative effect of the JO4 mutation on the usage of another Ad3 receptor: CD46.
Article
Virology
Jack R. Hemsath, A. Manuel Liaci, Jeffrey D. Rubin, Brian J. Parrett, Shao-Chia Lu, Tien Nguyen, Mallory A. Turner, Christopher Y. Chen, Karolina Cupelli, Vijay S. Reddy, Thilo Stehle, M. Kathryn Liszewski, John P. Atkinson, Michael A. Barry
Summary: This study investigates the usage of CD46 receptor by Ad26 virus in different administration routes and its impact on infection efficiency. The results show that Ad26 can use CD46 as a receptor but its usage varies depending on the administration route. Ectopic expression of CD46 on cells enhances Ad26 infection, while tumor injection or intravenous injection shows lower infection efficiency. High-dose intravenous injection of Ad26 induces liver enzyme release and reduces white blood cell counts but does not cause thrombocytopenia.
JOURNAL OF VIROLOGY
(2022)
Article
Cell Biology
Raphael L. Tsoukas, Wolfram Volkwein, Jian Gao, Maren Schiwon, Nora Bahlmann, Thomas Dittmar, Claudia Hagedorn, Eric Ehrke-Schulz, Wenli Zhang, Armin Baiker, Anja Ehrhardt
Summary: In this study, the authors systematically analyzed the receptor usage of different adenoviruses using a reporter gene-tagged adenovirus library and a human gene knockout model. They found that some adenoviruses are dependent on the CD46 or CAR receptor, and other receptors or attachment structures may also play a role in adenovirus transduction.
Article
Medicine, Research & Experimental
Chang Li, Hongjie Wang, Sucheol Gil, Audrey Germond, Connie Fountain, Audrey Baldessari, Jiho Kim, Zhinan Liu, Aphrodite Georgakopoulou, Stefan Radtke, Tamas Rasko, Amit Pande, Christina Chiang, Eli Chin, Evangelia Yannaki, Zsuzsanna Izsvak, Thalia Papayannopoulou, Hans-Peter Kiem, Andre Lieber
Summary: This study tested a new approach for in vivo hematopoietic stem cell transduction/selection in rhesus macaques. The results showed successful transduction of HSCs and increased levels of gamma-globin expressing red blood cells. Pre-treatment with dexamethasone and interleukin receptor blockers successfully blunted proinflammatory cytokine activation. The findings demonstrate the feasiblity of in vivo HSC gene therapy in humans without high-dose chemotherapy and HSC transplantation.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Medicine, Research & Experimental
Abdul Mohin Sajib, Payal Agarwal, Daniel J. Patton, Rebecca L. Nance, Natalie A. Stahr, Will P. Kretzschmar, Maninder Sandey, Bruce F. Smith
Summary: The study demonstrates a significantly improved and efficient method for editing adenoviruses using CRISPR/CAS9 technology to generate potentially therapeutic viral genomes in a shorter timeframe. The success of this targeted editing approach could have significant implications for gene therapy and virotherapy research aimed at treating cancer.
LABORATORY INVESTIGATION
(2021)
Article
Medicine, Research & Experimental
Patrick C. Freitag, Meike Kaulfuss, Lea Fluhler, Juliane Mietz, Fabian Weiss, Dominik Brucher, Jonas Kolibius, Sheena N. Smith, Christian Munz, Obinna Chijioke, Andreas Pluckthun
Summary: Clinical success in T cell therapy has prompted efforts to improve safety and efficacy, and expand its use in solid tumors. However, limitations in viral vectors, such as limited payload capacity and specificity of transduction, hinder progress in cell therapy. This study developed a combination of adapter constructs for targeted transduction of human T cells by adenoviral vectors, overcoming these limitations and increasing payload capacity. These findings provide a potential avenue to overcome current limitations of T cell therapy.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Nanoscience & Nanotechnology
Liqing Qi, Yuan Tian, Na Li, Menghan Mao, Xiaohong Fang, Da Han
Summary: The strategy of improving the binding affinity of drug molecules against targets has led to successful therapeutic applications. However, this affinity improvement can also result in on-target, off-tumor toxicity, which limits their clinical usage. In this study, a modular assembly strategy was proposed to create affinity-tunable DNA nanostructures that can immobilize multiple aptamers with different affinities to the antigen EpCAM. The theoretical model developed in this study demonstrated the variation of aptamer assembly affinity with antigen density and aptamer valency. Experimental results showed that this model can predict the minimum valency required for discriminating between EpCAMhigh and EpCAMlow cells in vitro and in vivo. The authors believe that this strategy has broad applications in nucleic acid-based delivery platforms for targeted therapy.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Multidisciplinary Sciences
Tomoko Nakanishi, Aya Maekawa, Mariko Suzuki, Hirotaka Tabata, Kumiko Sato, Mai Mori, Izumu Saito
Summary: The simultaneous expression of multiple guide RNAs is valuable for knocking out multiple genes and disrupting a gene effectively. The new method developed allows the construction of cosmids containing multiple gRNA-expressing units, leading to successful production of an adenovirus vector for animal experiments.
SCIENTIFIC REPORTS
(2021)
Review
Biotechnology & Applied Microbiology
Alexander Michels, Naphang Ho, Christian J. Buchholz
Summary: Chimeric antigen receptor (CAR) T cell therapy is extremely effective but complex and costly, not accessible to all who could benefit. Efforts are being made to simplify treatment by generating CAR T cells directly in the patient, which poses technical challenges but holds great clinical potential.
Article
Materials Science, Biomaterials
Xu-Ying Liu, Jing-Bo Yang, Cheng-Yan Wu, Quan Tang, Zhong-Lin Lu, Lan Lin
Summary: Six amphiphiles were designed and synthesized for synergistic anticancer gene therapy and photodynamic therapy. They exhibited strong AIE fluorescence emissions and efficient gene transfection, as well as the ability to deliver siRNA and generate reactive oxygen species for enhanced cancer therapy.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)
Article
Virology
Emily A. Bates, John R. Counsell, Sophie Alizert, Alexander T. Baker, Natalie Suff, Ashley Boyle, Angela C. Bradshaw, Simon N. Waddington, Stuart A. Nicklin, Andrew H. Baker, Alan L. Parker
Summary: Species D adenoviruses, such as human adenovirus type 49 (HAdV-D49), show promise for gene therapy applications due to their low pre-existing immunity rates. HAdV-D49 exhibits a broad range of cell transduction capabilities and interacts with various surface molecules for cell entry. Additionally, compared to adenovirus type 5, HAdV-D49 vectors demonstrate reduced liver targeting but maintain transduction of lung and spleen tissues.
Article
Biochemistry & Molecular Biology
Ana Alfano, Eduardo G. A. Cafferata, Mariela Gangemi, Alejandro Nicola Candia, Cristian M. Malnero, Ismael Bermudez, Mauricio Vargas Lopez, Gregorio David Rios, Cecilia Rotondaro, Nicasio Cuneo, David T. Curiel, Osvaldo L. Podhajcer, Maria Veronica Lopez
Summary: More than one million women worldwide are diagnosed with gynecological cancer each year. Most cases are diagnosed at a late stage due to a lack of symptoms or limited access to prevention in low-resource countries. The oncolytic adenovirus AR2011 has shown promising results in inhibiting the growth of ovarian, uterine, and cervical cancers in vitro, as well as synergizing with chemotherapy. In animal models, AR2011 has demonstrated efficacy in treating ovarian cancer and inducing an abscopal effect. It is a potential novel medicine for intraperitoneal disseminated ovarian cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Dapeng Li, Robert J. Edwards, Kartik Manne, David R. Martinez, Alexandra Schafer, S. Munir Alam, Kevin Wiehe, Xiaozhi Lu, Robert Parks, Laura L. Sutherland, Thomas H. Oguin, Charlene McDanal, Lautaro G. Perez, Katayoun Mansouri, Sophie M. C. Gobeil, Katarzyna Janowska, Victoria Stalls, Megan Kopp, Fangping Cai, Esther Lee, Andrew Foulger, Giovanna E. Hernandez, Aja Sanzone, Kedamawit Tilahun, Chuancang Jiang, Longping Tse, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Kenneth Cronin, Victoria Gee-Lai, Margaret Deyton, Maggie Barr, Tarra Von Holle, Andrew N. Macintyre, Erica Stover, Jared Feldman, Blake M. Hauser, Timothy M. Caradonna, Trevor D. Scobey, Wes Rountree, Yunfei Wang, M. Anthony Moody, Derek W. Cain, C. Todd DeMarco, Thomas N. Denny, Christopher W. Woods, Elizabeth W. Petzold, Aaron G. Schmidt, I-Ting Teng, Tongqing Zhou, Peter D. Kwong, John R. Mascola, Barney S. Graham, Ian N. Moore, Robert Seder, Hanne Andersen, Mark G. Lewis, David C. Montefiori, Gregory D. Sempowski, Ralph S. Baric, Priyamvada Acharya, Barton F. Haynes, Kevin O. Saunders
Summary: Research has shown that some SARS-CoV-2 neutralizing antibodies can enhance virus infection in vitro, but in monkeys and mice, these antibodies can still protect against SARS-CoV-2. However, out of 46 monkeys infused with enhancing antibodies, three showed higher lung inflammation scores compared to controls.
Article
Oncology
Tingyu Li, Jinbo Fang, Jihao Chu, Xing Liu, Yiquan Li, Yilong Zhu, Shanzhi Li, Zhiru Xiu, Yaru Li, Ningyi Jin, Guangzhe Zhu, Lili Sun, Xiao Li
Summary: The study demonstrates the important role of Ad-VT in synergistically inhibiting tumors when combined with Etoposide, while reducing the toxicity of Etoposide to normal cells.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eric G. Romanowski, Kathleen A. Yates, Y. Jerold Gordon
Summary: CPE-C is an antiviral that has shown potent activity against adenoviruses, a major cause of ocular viral infections. In vitro and in vivo experiments demonstrated its strong antiviral activity and low ocular toxicity in rabbit eyes.
Article
Medicine, Research & Experimental
Tien-Ching Chang, Bing-Mae Chen, Jer-Yuan Wu, Tian-Lu Cheng, Steve Roffler
Summary: Antibodies that bind polyethylene glycol (PEG) can accelerate the clearance of pegylated medicines, with higher affinity antibodies leading to greater clearance and reduced drug efficacy. The molar ratio of high affinity anti-PEG antibodies to PEG-EPO correlates with accelerated blood clearance in mice.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Cardiac & Cardiovascular Systems
Lisa M. Becker, Shiau-Haln Chen, Julie Rodor, Laura P. M. H. de Rooij, Andrew H. Baker, Peter Carmeliet
Summary: Endothelial cells play a crucial role in the human body but their heterogeneity poses challenges in therapy. Recent studies have revealed the diverse functions of endothelial cells and their roles in diseases, and proposed strategies to deal with this heterogeneity.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Hongjie Wang, Chang Li, Adebimpe O. Obadan, Hannah Frizzell, Tien-Ying Hsiang, Sucheol Gil, Audrey Germond, Connie Fountain, Audrey Baldessari, Steve Roffler, Hans-Peter Kiem, Deborah H. Fuller, Andre Lieber
Summary: This study introduces a new approach for the prevention and treatment of SARS-CoV2 using gene therapy, and evaluates the safety of this method. The results show that this method can provide long-term protection against SARS-CoV2 infection, and has demonstrated promising results in mouse and rhesus macaque models. However, the antiviral efficacy of this approach needs to be improved.
HUMAN GENE THERAPY
(2022)
Article
Cardiac & Cardiovascular Systems
Ziwen Li, Emmanouil G. Solomonidis, Bronwyn Berkeley, Michelle Nga Huen Tang, Katherine Ross Stewart, Daniel Perez-Vicencio, Ian R. McCracken, Ana Mishel Spiroski, Gillian A. Gray, Anna K. Barton, Stephanie L. Sellers, Paul R. Riley, Andrew H. Baker, Mairi Brittan
Summary: We present a high-resolution single-cell meta-atlas of healthy and injured coronary endothelial cells in the mouse and human heart, revealing a suite of novel targets with great potential to promote vascular regeneration, and providing a rich resource for therapeutic development.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Trisha Singh, Shruti Joshi, Lucy E. Kershaw, Andy H. Baker, Gerry P. McCann, Dana K. Dawson, Marc R. Dweck, Scott I. Semple, David E. Newby
Summary: Patients with takotsubo syndrome exhibit significant myocardial manganese uptake abnormality, most pronounced in the acute phase but persisting for at least 3 months despite apparent restoration of normal left ventricular ejection fraction.
Article
Gastroenterology & Hepatology
Fenella K. S. Welsh, Caoimhe M. Walsh, Kandiah Chandrakumaran, Wasula S. Rathnaweera, Ashok Roy, Jane Needham, Adrian B. Cresswell, John H. McVey, Myrddin Rees
Summary: This study observed patients undergoing hepatectomy for colorectal metastases and found that there is a risk of thrombosis before the surgery, which is further increased by the hepatectomy. Based on the results, it is suggested that chemical thromboprophylaxis should be considered early in the patient pathway.
Article
Cardiac & Cardiovascular Systems
Ana-Mishel Spiroski, Ian R. McCracken, Adrian Thomson, Marlene Magalhaes-Pinto, Mukesh K. Lalwani, Kathryn J. Newton, Eileen Miller, Cecile Benezech, Patrick Hadoke, Mairi Brittan, Joanne C. Mountford, Abdelaziz Beqqali, Gillian A. Gray, Andrew H. Baker
Summary: This study investigated the tissue remodeling effects of human embryonic stem cell-derived endothelial cell product (hESC-ECP) therapy on infarcted heart and found that it reduces infarct size and preserves functional myocardium. By examining the interactions between cells and immune regulation, this research provides new therapeutic avenues for improving cardiac outcomes following myocardial infarction.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Kim van Kuijk, Ian R. McCracken, Renee J. H. A. Tillie, Sebastiaan E. J. Asselberghs, Dlzar A. Kheder, Stan Muitjens, Han Jin, Richard S. Taylor, Ruud Wichers Schreur, Christoph Kuppe, Ross Dobie, Prakesh Ramachandran, Marion J. Gijbels, Lieve Temmerman, Phoebe M. Kirkwoord, Joris Luyten, Yanming Li, Heidi Noels, Pieter Goossens, John R. Wilson-Kanamori, Leon J. Schurgers, Ying H. Shen, Barend M. E. Mees, Erik A. L. Biessen, Neil C. Henderson, Rafael Kramann, Andrew H. Baker, Judith C. Sluimer
Summary: This study established specific markers for adventitial fibroblasts and analyzed their heterogeneity in response to cardiovascular diseases and risk factors. The findings revealed the functional diversity and gene expression differences among different fibroblast clusters, which are associated with cardiovascular diseases. Therefore, this study is important for understanding cardiovascular diseases and developing targeted therapies.
CARDIOVASCULAR RESEARCH
(2023)
Letter
Cardiac & Cardiovascular Systems
Julie Rodor, Shiau-Haln Chen, Andrew H. Baker
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Daniel Stone, Martine Aubert, Keith R. Jerome
Summary: More than 15 years after the first observation of hepatotoxicity following AAV vector administration, recent reports have highlighted the potential impact of AAV-associated neurotoxicity. Both pre-clinical studies and clinical trials have shown neurotoxicity in peripheral nerve ganglia, spinal cord, and direct brain injection. Neurotoxic events vary across species and may be underdiagnosed. This review discusses animal models, causes, consequences, and approaches to mitigate AAV-associated neurotoxicity.
Article
Multidisciplinary Sciences
T. Singh, S. Joshi, M. N. Meah, N. B. Spath, G. Papanastasiou, L. E. Kershaw, A. H. Baker, M. R. Dweck, D. E. Newby, S. I. Semple
Summary: Manganese-enhanced magnetic resonance imaging can serve as a surrogate measure for myocardial calcium handling. The repeatability and reproducibility of this imaging method have been investigated in a study involving 68 participants. The results demonstrate excellent repeatability and reproducibility in healthy myocardium, but slightly lower consistency in patients with dilated cardiomyopathy.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Hongjie Wang, Aphrodite Georgakopoulou, Wenli Zhang, Jiho Kim, Sucheol Gil, Anja Ehrhardt, Andre Lieber
Summary: In previous studies, safe and efficient in vivo hematopoietic stem cell (HSC) transduction was achieved by intravenously injecting helper-dependent adenovirus HDAd5/35++ vectors in mobilized mice and macaques. To address the impact of anti-Ad5/HDAd5/35++ neutralizing serum antibodies in humans, HSC-retargeted HDAd6/35++ vectors derived from serotype 6 were generated. Compared with HDAd5/35++, HDAd6/35++ showed a lower prevalence and titers of serum anti-HDAd6/35++ in human samples. In vitro studies demonstrated efficient transduction of human and rhesus CD34+ cells by HDAd6/35++ vectors.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Microbiology
Rossana Colon-Thillet, Daniel Stone, Michelle A. Loprieno, Lindsay Klouser, Pavitra Roychoudhury, Tracy K. Santo, Hong Xie, Laurence Stensland, Sarah L. Upham, Gregory Pepper, Meei-Li Huang, Martine Aubert, Keith R. Jerome
Summary: The NSG-PiZ liver-humanized mouse model, which is relatively inexpensive and simple to establish, can support chronic HBV infection. This model provides a viable and cost-effective alternative to other liver-humanized mouse models for studying HBV disease pathogenesis and antiviral therapy.
MICROBIOLOGY SPECTRUM
(2023)
Article
Gastroenterology & Hepatology
Daniel Stone, Nadja Meumann, Anne-Sophie Kuhlmann, Christopher W. Peterson, Hong Xie, Pavitra Roychoudhury, Michelle A. Loprieno, Xuan-Khang Vu, Daniel E. Strongin, Elizabeth J. Kenkel, Anoria Haick, Laurence Stensland, Willimark M. Obenza, Jacob Parrott, Veronica Nelson, Robert D. Murnane, Meei-Li Huang, Martine Aubert, Hans-Peter Kiem, Hildegard Buening, Keith R. Jerome
Summary: In order to optimize the AAV vector selection process, a multiplex barcoding approach was developed to simultaneously evaluate the in vivo performance of various AAV vectors in multiple organs. The findings showed differences in biodistribution and tissue transduction patterns among animals, influenced by their distinctive serological status.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Cardiac & Cardiovascular Systems
Frederike Boos, James A. Oo, Timothy Warwick, Stefan Guenther, Judit Izquierdo Ponce, Melina Lopez, Diba Rafii, Giulia Buchmann, Minh Duc Pham, Zahraa S. Msheik, Tianfu Li, Sandra Seredinski, Shaza Haydar, Sepide Kashefiolasl, Karl H. Plate, Ruediger Behr, Matthias Mietsch, Jaya Krishnan, Soni S. Pullamsetti, Sofia-Iris Bibli, Rabea Hinkel, Andrew H. Baker, Reinier A. Boon, Marcel H. Schulz, Ilka Wittig, Francis J. Miller, Ralf P. Brandes, Matthias S. Leisegang
Summary: Long non-coding RNA LINC00607 is highly enriched in human endothelial cells and plays a regulatory role in angiogenesis by interacting with chromatin remodeler BRG1 to maintain ERG target gene transcription. Knockdown or knockout of LINC00607 attenuates VEGF-A-induced angiogenic sprouting and integration into vascular networks. Overexpression of LINC00607 restores normal endothelial function. These findings provide new insights into the role of lncRNAs in endothelial cells and their potential implications in cardiovascular disease.
BASIC RESEARCH IN CARDIOLOGY
(2023)
