Replication deficient adenovirus vectors are frequently used tools for the delivery of transgenes in vitro and in vivo. In addition, several therapeutic products based on adenovirus are under clinical development. This review outlines adenovirus vector production discussing different vector types, available production cell lines and state of the art of production process development and purification.
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Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adults.
mSphere
December 2024
International Vaccine Institute, Seoul, South Korea.
AdCLD-CoV19-1, a chimeric adenovirus-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, was previously reported to elicit robust antibody responses in mice and non-human primates after a single dose. In this study, we conducted a systems serology analysis to investigate changes in humoral immune responses induced by varying doses of the AdCLD-CoV19-1 vaccine in a phase I clinical trial. Serum samples from participants receiving either a low or a high dose of the vaccine were analyzed for antibody features against prototype SARS-CoV-2 spike (S) domains (full-length S, S1, S2, and receptor binding domain), as well as Fc receptor binding and effector functions.
View Article and Find Full Text PDFGeneration of a SARS-CoV-2-susceptible mouse model using adenovirus vector expressing human angiotensin-converting enzyme 2 driven by an elongation factor 1α promoter with leftward orientation.
Front Immunol
December 2024
Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Introduction: To analyze the molecular pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a small animal model such as mice is needed: human angiotensin converting enzyme 2 (hACE2), the receptor of SARS-CoV-2, needs to be expressed in the respiratory tract of mice.
Methods: We conferred SARS-CoV-2 susceptibility in mice by using an adenoviral vector expressing hACE2 driven by an elongation factor 1α (EF1α) promoter with a leftward orientation.
Results: In this model, severe pneumonia like human COVID-19 was observed in SARS-CoV-2-infected mice, which was confirmed by dramatic infiltration of inflammatory cells in the lung with efficient viral replication.
Two live attenuated vaccines (LAVs), LMA and LMP, were evaluated alone or in combination with a trivalent adenoviral vector-based vaccine (Ad5-YFV) for their efficacy and immune responses in wild type (WT) and interferon gamma (IFNγ) knockout (KO) mice in a C57BL/6 background. While LMA and LMP are triple deletion mutants of CO92 strain, Ad5-YFV incorporates three protective plague immunogens. An impressive 80-100% protection was observed in all vaccinated animals against highly lethal intranasal challenge doses of parental CO92.
View Article and Find Full Text PDFHMGB1 Promotes Accelerated Fracture Healing in Traumatic Brain Injury through PINK1/Parkin-Mediated Mitochondrial Autophagy.
Biol Pharm Bull
December 2024
Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University.
We aimed to investigate the mechanism of high mobility group box 1 (HMGB1) in the accelerated fracture healing process during Traumatic brain injury (TBI). The lateral ventricles of mice in the TBI model group were injected with adenovirus-packaged short hairpin RNA (shRNA)-HMGB1 or overexpressing (ov)-HMGB1 vector. We found HMGB1 levels were higher in bone tissue at the fracture end of TBI combined with fracture model mice.
View Article and Find Full Text PDFAn adenoviral vector encoding an inflammation-inducible antagonist, HMGB1 Box A, as a novel therapeutic approach to inflammatory diseases.
mBio
December 2024
Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, Maryland, USA.
Influenza, as well as other respiratory viruses, can trigger local and systemic inflammation resulting in an overall "cytokine storm" that produces serious outcomes such as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We hypothesized that gene therapy platforms could be useful in these cases if the production of an anti-inflammatory protein reflects the intensity and duration of the inflammatory condition. The recombinant protein would be produced and released only in the presence of the inciting stimulus, avoiding immunosuppression or other unwanted side effects that may occur when treating infectious diseases with anti-inflammatory drugs.
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