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
Audiology & Speech-Language Pathology
Osama Tarabichi, Tatiana Correa, Emre Kul, Stacia Phillips, Bahaa Darkazanly, Samuel M. Young Jr, Marlan R. Hansen
Summary: Viral vector gene therapy using Helper-dependent adenoviral vectors (HdAd) shows potential for treating hearing loss. HdAd vectors can express large or multiple genes in a cell-type specific manner. Two HdAd vectors, HdAd5 and a chimeric HdAd 5/35, were created and delivered into mice to evaluate their efficacy in inner ear gene therapy. Both HdAd vectors successfully transduced multiple cell types in the cochlea, suggesting their promise in treating hearing loss.
Article
Oncology
Amanda Rosewell Shaw, Caroline Porter, Greyson Biegert, Lisa Jatta, Masataka Suzuki
Summary: Solid tumors are highly immunosuppressive and require simultaneous targeting of multiple inhibitory mechanisms for successful cancer immunotherapy. Adenoviral vectors have the ability to stimulate multiple immune pathways and are promising cancer gene therapy vectors. Helper-dependent adenoviral vectors can express multiple transgenes for immunomodulation in tumors.
Article
Immunology
Sarah Sanchez, Nicole Palacio, Tanushree Dangi, Thomas Ciucci, Pablo Penaloza-MacMaster
Summary: Research conducted on mice showed that using a lower dose of vaccine for the prime dose resulted in initially lower immune responses, but upon boosting with the standard dose, exhibited stronger immune memory and functional capacity. These findings suggest a potential advantage of fractionating vaccine prime doses and may require a reevaluation of vaccine trial protocols for SARS-CoV-2 and other pathogens.
SCIENCE IMMUNOLOGY
(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
Biochemical Research Methods
Trevor J. Gonzalez, Aaron Mitchell-Dick, Leo O. Blondel, Marco M. Fanous, Joshua A. Hull, Daniel K. Oh, Sven Moller-Tank, Ruth M. Castellanos Rivera, Jorge A. Piedrahita, Aravind Asokan
Summary: This article describes a structure-guided library approach to evolve new AAV capsids with improved characteristics. The method can enhance gene transfer efficiency, immune evasion, and can be adapted for genetic manipulation in animal models and development of human gene therapies.
Article
Ophthalmology
Ian C. Han, Erin R. Burnight, Emily E. Kaalberg, Timothy M. Boyce, Edwin E. Stone, John H. Fingert, Robert F. Mullins, Budd A. Tucker, Luke A. Wiley
Summary: This study evaluated the retinal tropism of two chimeric helper-dependent adenoviruses in human retinal explants and rats, showing that these vectors can transduce specific retinal cell types including Muller cells and retinal ganglion cells. Differences in tropism were observed between human and rat models, highlighting the importance of using human explants for testing vectors for potential human gene therapy.
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
(2021)
Article
Engineering, Chemical
Mafalda G. Moleirinho, Sean Feast, Ana S. Moreira, Ricardo J. S. Silva, Paula M. Alves, Manuel J. T. Carrondo, Tim Huber, Conan Fee, Cristina Peixoto
Summary: Advancements in designing new biotherapeutic products using viral particles have been witnessed in recent decades, with the limitations of manufacturing these particles often related to purification processes. This study demonstrates the successful use of 3D-printed cellulose chromatographic columns functionalized with different ligands for the purification of oncolytic adenovirus and lentiviral vectors, achieving efficient separations with high recovery yields. The application of 3D printing technologies in viral vector manufacturing shows potential to improve downstream process efficiency.
SEPARATION AND PURIFICATION TECHNOLOGY
(2021)
Article
Medicine, Research & Experimental
Dominik Brucher, Nicole Kirchhammer, Sheena N. Smith, Jatina Schumacher, Nina Schumacher, Jonas Kolibius, Patrick C. Freitag, Markus Schmid, Fabian Weiss, Corina Keller, Melanie Grove, Urs F. Greber, Alfred Zippelius, Andreas Pluckthun
Summary: The iMATCH platform developed in this study allows for the rapid generation of high-purity, high-quantity HCAdVs encoding therapeutic combinations within 3 weeks. This system efficiently integrates up to four expression cassettes and enables organ-specific targeting.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Payal Agarwal, Elizabeth A. Gammon, Maninder Sandey, Stephanie S. Lindley, Jey W. Koehler, Brad M. Matz, Annette N. Smith, Elena A. Kashentseva, Igor P. Dmitriev, David T. Curiel, Bruce F. Smith
Summary: Osteosarcoma is a common neoplasm in dogs with limited treatment options. The use of OC-CAVE1 showed minimal virus shedding and short duration of virus presence in blood. Although some immune response parameters were altered, administration of OC-CAVE1 did not lead to increased survival duration in most patients, although two dogs achieved survival times exceeding 1 year.
Article
Virology
Emeline Goffin, Xiang Du, Silvio Hemmi, Benedicte Machiels, Laurent Gillet
Summary: Developing effective and flexible vaccine platforms, particularly for influenza vaccines that require annual renewal, is a significant public health challenge. Adenoviruses show promise as an ideal backbone for oral replicating vector vaccines, but research is hindered by the inefficiency of human adenovirus replication in laboratory animals.
JOURNAL OF VIROLOGY
(2023)
Article
Genetics & Heredity
Abdulaziz Almuqrin, Andrew D. Davidson, Maia Kavanagh Williamson, Philip A. Lewis, Kate J. Heesom, Susan Morris, Sarah C. Gilbert, David A. Matthews
Summary: The ChAdOx1 nCoV-19 vaccine demonstrated expected transcriptomic and proteomic profiles in cell culture, with the SARS-CoV-2 S coding transcript dominating in all cell lines and rare adenovirus gene expression in A549 cells comparatively. This study highlights the potential for future viral vaccine vector design based on detailed insights gained from advanced transcriptomic and proteomic analyses.
Article
Microbiology
Min-Wen Ku, Maryline Bourgine, Pierre Authie, Jodie Lopez, Kirill Nemirov, Fanny Moncoq, Amandine Noirat, Benjamin Vesin, Fabien Nevo, Catherine Blanc, Philippe Souque, Houda Tabbal, Emeline Simon, David Hardy, Marine Le Dudal, Francoise Guinet, Laurence Fiette, Hugo Mouquet, Francois Anna, Annette Martin, Nicolas Escriou, Laleh Majlessi, Pierre Charneau
Summary: Vaccination using a lentiviral vector to induce neutralizing antibodies against SARS-CoV-2 provides partial protection when administered systemically, but intranasal immunization results in a significant decrease in lung viral load and reduced local inflammation. Integrative and non-integrative lentiviral platforms both show strong vaccine efficacy against COVID-19 in golden hamsters, highlighting the potential of intranasal vaccination as a powerful approach.
CELL HOST & MICROBE
(2021)
Article
Multidisciplinary Sciences
Elena Navarro-Guerrero, Chwen Tay, Justin P. Whalley, Sally A. Cowley, Ben Davies, Julian C. Knight, Daniel Ebner
Summary: This study presents an efficient lentiviral transduction protocol for delivering CRISPR/Cas9 to macrophages derived from human iPSC, enabling systematic exploration of macrophage involvement in human disease development using genome editing techniques.
SCIENTIFIC REPORTS
(2021)
Article
Construction & Building Technology
Wen Zhou, Wes McGee, He Zhu, H. Suleyman Gokce, Victor C. Li
Summary: This paper investigates and quantifies the buildability of printable engineered cementitious composites at both the material and structural scales. The load capacity and deformation resistance of fresh ECC material are studied, and a time-dependent strain-stress model is proposed to predict vertical deformation of 3D printed structures. The approach of predicting self-buckling failure based on stiffness evolution is also validated.
CEMENT & CONCRETE COMPOSITES
(2022)
Article
Medicine, Research & Experimental
Bachirou Tinto, Dramane Kania, Therese Samdapawinde Kagone, Amadou Dicko, Isidore Traore, Nathalie de Rekeneire, Brice Wilfried Bicaba, Herve Hien, Philippe Van de Perre, Yannick Simonin, Sara Salinas
Summary: Dengue fever diagnosis in West Africa is challenging due to similar clinical presentations with other diseases, making biological diagnosis the only alternative. However, resource-limited countries often lack high-quality equipment and trained personnel, leading to misdiagnosis of dengue fever as malaria and serious health consequences for patients.
M S-MEDECINE SCIENCES
(2022)
Article
Virology
Orianne Constant, Jonathan Barthelemy, Anna Nagy, Sara Salinas, Yannick Simonin
Summary: The study shows that increased levels of inflammatory cytokines and neuronal factors in patients infected with West Nile virus (WNV) are associated with the development of severe neurological impairments. These biomarkers could play a crucial role in patient monitoring, improving care, and preventing undesirable outcomes.
Review
Immunology
Orianne Constant, Ghizlane Maarifi, Fabien P. Blanchet, Philippe van de Perre, Yannick Simonin, Sara Salinas
Summary: This review highlights the important contribution of dendritic cells in the development and consequences of viral brain infections.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Barbara Fernandes, Marcos Sousa, Rute Castro, Anja Schaefer, Julia Hauser, Kai Schulze, Mario Amacker, Marco Tamborrini, Gerd Pluschke, Paula M. Alves, Sylvain Fleury, Antonio Roldao
Summary: This study explores different insect cell lines, culture conditions, and purification strategies to develop a scalable, high-yield, and high-quality Plasmodium falciparum candidate antigen for a malaria vaccine. Results show that adding antioxidants improves PfCyRPA production, and the 4x-His affinity tag has the highest purification recovery and production yield. Additionally, PfCyRPA expressed in insect cells shows no difference in protein quality and stability compared to expression in human cells.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Physiology
Ana F. Louro, Nikolaus Virgolini, Marta A. Paiva, Ines A. Isidro, Paula M. Alves, Patricia Gomes-Alves, Margarida Serra
Summary: Extracellular Vesicles (EV) play a critical role in regulating regenerative processes in wounded tissues through cell-to-cell communication. This study investigated the piRNA profiles of EV derived from different stages of differentiation and maturation, and found significant differences between piRNA and miRNA expression. Only a small number of piRNA were found to be deregulated in EV. These results provide valuable information for further studying the role of piRNA in the bioactivity and therapeutic potential of EV.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Barbara Fernandes, Ricardo Correia, Paula M. Alves, Antonio Roldao
Summary: This study developed a method for continuous production of VLPs using stable insect cells at high cell density and evaluated the impact of cell retention devices and cell-specific perfusion rate on production kinetics. Manipulating the cell-specific perfusion rate can significantly increase production yields and make stable insect cells an attractive alternative to the insect cell-baculovirus expression vector system.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Ricardo Correia, Barbara Fernandes, Rute Castro, Hikaru Nagaoka, Eizo Takashima, Takafumi Tsuboi, Akihisa Fukushima, Nicola K. Viebig, Hilde Depraetere, Paula M. Alves, Antonio Roldao
Summary: This study improved the production of the malaria vaccine candidate PfRipr5 by using insect and human cell hosts as well as process-optimizing strategies. Maximizing protein expression and improving expression vector and culture conditions significantly increased the production yield of PfRipr5.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Virology
Marco Silvano, Ricardo Correia, Nikolaus Virgolini, Colin Clarke, Paula M. Alves, Ines A. Isidro, Antonio Roldao
Summary: This study investigates the gene expression patterns associated with high-producer insect cells adapted to neutral pH during the production of influenza HA-VLPs. The results show differential expression of host cell genes and baculovirus genes, with enrichment of pathways related to metabolism and protein folding. These findings contribute to our understanding of the biological mechanisms of insect cells during baculovirus-mediated expression.
Article
Oncology
Rita Mendes, Goncalo Graca, Fernanda Silva, Ana C. L. Guerreiro, Patricia Gomes-Alves, Jacinta Serpa, Erwin R. Boghaert, Paula M. Alves, Ana Felix, Catarina Brito, Ines A. Isidro
Summary: This study explores metabolic signatures of chemosensitivity and resistance in ovarian cancer by exposing patient-derived tumor tissue to chemotherapy drugs. The study identifies potential metabolic biomarkers of drug response and establishes a platform to explore metabolic features of the tumor microenvironment. Predicting patient response to treatment and chemoresistance remains a major challenge in oncology.
Article
Immunology
Orianne Constant, Ghizlane Maarifi, Jonathan Barthelemy, Marie-France Martin, Bachirou Tinto, Giovanni Savini, Philippe Van de Perre, Sebastien Nisole, Yannick Simonin, Sara Salinas
Summary: This study characterizes and compares the infectivity, innate immunity and inflammatory responses, and immune cell recruitment of Usutu and West Nile viruses in the blood-brain barrier. Both viruses can infect the blood-brain barrier, but with different consequences. Usutu virus does not strongly affect the endothelium integrity but induces neuroinflammation and immune cell recruitment. In contrast, West Nile virus infection results in endothelium impairment, potent neuroinflammation, and immune cell recruitment.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Physics, Applied
Carles Bosch, Joerg Lindenau, Alexandra Pacureanu, Christopher J. Peddie, Marta Majkut, Andrew C. Douglas, Raffaella Carzaniga, Alexander Rack, Lucy Collinson, Andreas T. Schaefer, Heiko Stegmann
Summary: Correlative multimodal imaging is a valuable method for investigating complex structural relations in life sciences. It requires establishing sample preparation workflows that are compatible with multiple imaging techniques. This can involve imaging a fluorescently labeled region of interest in a biological soft tissue sample with light microscopy before staining the specimen with heavy metals for higher resolution structural imaging.
APPLIED PHYSICS LETTERS
(2023)
Article
Multidisciplinary Sciences
Jane C. Stinchcombe, Yukako Asano, Christopher J. G. Kaufman, Kristin Bohlig, Christopher J. Peddie, Lucy M. Collinson, Andre Nadler, Gillian M. Griffiths
Summary: Cytotoxic T lymphocytes (CTLs) kill virus-infected and cancer cells through T cell receptor (TCR) recognition. Activation of TCR triggers the production of diacylglycerol (DAG) and shedding of activated TCRs into DAG-enriched ectosomes at the immune synapse, rather than internalization through endocytosis. The budding ectosomes are then endocytosed by target cells, terminating TCR signaling and disconnecting CTLs from target cells for serial killing. Ectocytosis therefore limits TCR signaling.
Article
Biology
Juan Carlos Cerpa, Alessandro Piccin, Margot Dehove, Marina Lavigne, Eric J. Kremer, Mathieu Wolff, Shauna L. Parkes, Etienne Coutureau
Summary: Organisms need to track the relationship between actions and consequences in order to make decisions, which relies on circuits in the brain. There is functional heterogeneity within certain areas of the brain in rodents. Neuromodulatory agents play a crucial role in prefrontal functions and behavioral flexibility.
Article
Biochemistry & Molecular Biology
Gabriela Silva, Ana F. Rodrigues, Susana Ferreira, Carolina Matos, Rute P. Eleuterio, Goncalo Marques, Khrystyna Kucheryava, Ana R. Lemos, Pedro M. F. Sousa, Rute Castro, Ana Barbas, Daniel Simao, Paula M. Alves
Summary: In this study, specific anti-JAG1 single-chain variable fragments (scFvs) were identified and used to create chimeric antigen receptor (CAR) T cells that exhibited cytotoxicity against JAG1-positive cells, suggesting their potential for tumor treatment.
Meeting Abstract
Cell & Tissue Engineering
Henrique V. Almeida, Miguel Tenreiro, Ana F. Louro, Bernardo Abecasis, Deolinda Santinha, Tomas Calmeiro, Elvira Fortunato, Lino Ferreira, Paula M. Alves, Margarida Serra
TISSUE ENGINEERING PART A
(2022)