Article
Medicine, General & Internal
Estrella Lopez-Gordo, Alejandro Orlowski, Arthur Wang, Alan Weinberg, Susmita Sahoo, Thomas Weber
Summary: Studies show that AAV serotypes that bind to N-linked sialic acid have significantly lower transduction in the hearts of CMAH(-/-) mice, while skeletal muscle transduction by AAV5 is nearly 30 times higher. Importantly, the tropism of AAV and expression distribution in different organs are also affected.
FRONTIERS IN MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Amelie Bauer, Matteo Puglisi, Dennis Nagl, Joel A. Schick, Thomas Werner, Andreas Klingl, Jihad El Andari, Veit Hornung, Horst Kessler, Magdalena Goetz, Dirk Grimm, Ruth Brack-Werner
Summary: Astrocytes play crucial roles in the central nervous system and are involved in various CNS diseases. This study focuses on astrocyte-centered diseases and the need for effective and well-characterized gene transfer vectors. The findings highlight the use of a synthetic peptide-displaying AAV9 variant, rAAV9P1, which was shown to efficiently target and transduce human astrocytes. The study also identifies the specific receptors and intracellular pathways utilized by rAAV9P1 for astrocyte targeting. These results enhance our understanding of synthetic AAV vectors for astrocytes and their potential applications in research and medicine.
Article
Virology
Shannah Gates, Julien Andreani, Rebecca Dewar, Donald B. Smith, Kate Templeton, Harry T. Child, Judy Breuer, Tanya Golubchik, Irene Bassano, Matthew J. Wade, Aaron R. Jeffries, Peter Simmonds, Heli Harvala
Summary: Over 1000 cases of unexplained severe acute hepatitis in children have been reported worldwide, and our study aimed to investigate the epidemiology of adeno-associated virus type 2 (AAV2) infection in the United Kingdom. We collected pediatric respiratory samples and wastewater samples from London and tested them for AAV2. The detection frequency of AAV2 was significantly higher in 2022 samples compared to samples from 2009-2013, and it was most commonly found in children with adenovirus (AdV) infection of species C in 2022.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Microbiology
Sereina O. Sutter, Anouk Lkharrazi, Elisabeth M. Schraner, Kevin Michaelsen, Anita Felicitas Meier, Jennifer Marx, Bernd Vogt, Hildegard Buning, Cornel Fraefel
Summary: In this study, we provide evidence that the uncoating of the AAV2 virus occurs in a stepwise process, which is completed in the nucleolus and supported by alterations of the nucleolar morphology.
Article
Virology
Shonisani Wendy Limani, Njabulo Mnyandu, Abdullah Ely, Reubina Wadee, Anna Kramvis, Patrick Arbuthnot, Mohube Betty Maepa
Summary: The study demonstrated the use of recombinant adeno-associated viruses (AAVs) to model the replication of different hepatitis B virus (HBV) subgenotypes, showcasing the efficacy of the AAV8-A1 murine model for anti-HBV drug development.
Article
Biotechnology & Applied Microbiology
Daniel Stone, Elizabeth J. Kenkel, Michelle A. Loprieno, Motoko Tanaka, Harshana S. De Silva Feelixge, Arjun J. Kumar, Laurence Stensland, Willimark M. Obenza, Solomon Wangari, Chul Y. Ahrens, Robert D. Murnane, Christopher W. Peterson, Hans-Peter Kiem, Meei-Li Huang, Martine Aubert, Shiu-Lok Hu, Keith R. Jerome
Summary: The study on AAV6 and targeted AAV6 derivatives in rhesus macaques suggests that immunosuppression may enhance gene delivery efficiency, but safety concerns remain to be addressed.
HUMAN GENE THERAPY
(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
Virology
Guiqing Hu, Mark A. Silveria, Grant M. Zane, Michael S. Chapman, Scott M. Stagg
Summary: AAV is a leading gene therapy vector with 150 clinical trials for 30 diseases currently underway. Immunotoxicity at high doses used to overcome inefficient transduction has occasionally proven fatal and highlighted gaps in fundamental virology. Cryo-electron microscopy and cryo-electron tomography have revealed the interaction between AAV and its receptor, as well as the complexity of their structures.
JOURNAL OF VIROLOGY
(2022)
Article
Medicine, Research & Experimental
Sunghee Chai, Mason Norgard, Bin Li, David Enicks, Daniel L. Marks, Markus Grompe
Summary: Two small promoters have been discovered that can enable larger transgene expression than standard promoters, expanding the potential of clinical gene therapy.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
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)
Review
Chemistry, Multidisciplinary
Wenli Chen, Shun Yao, Jie Wan, Yu Tian, Lan Huang, Shanshan Wang, Farhana Akter, Yinqiu Wu, Yizheng Yao, Xiaochun Zhang
Summary: This review discusses various approaches to improve transportation of therapeutic agents to the CNS, focusing on the advantages of using BBB-crossing AAVs as gene delivery vectors and the different types of BBB-AAV vectors that have been developed for potential applications in CNS diseases.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Microbiology
Edward E. Large, Michael S. Chapman
Summary: Adeno-associated viruses (AAV) are widely used for gene therapy, and monoclonal antibodies against various AAV serotypes have been developed. Previous studies suggested that neutralizing antibodies inhibit binding to glycan receptors or interfere with post-entry steps. However, recent research has identified a protein receptor and revealed that antibody interference with protein receptor binding may be the predominant mechanism of neutralization.
FRONTIERS IN MICROBIOLOGY
(2023)
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
Chi Heon Kim, Colleen Oliver, Hamid Dar, Hicham Drissi, Steven M. Presciutti
Summary: Intervertebral disc degeneration is a major cause of low back pain worldwide. In this study, the researchers investigated the use of adenoassociated virus (AAV) as a tool for gene transfer in the intervertebral disc. They compared different AAV serotypes and parameters, and found that AAV6 with a CAG promoter at a titer of 1011 GC/mL achieved high transduction efficiency and low toxicity in murine nucleus pulposus cells. They also demonstrated the use of small cell permeabilization peptides to boost transduction efficiency, and utilized optical tissue clearing and three-dimensional lightsheet microscopy to visualize tissue and cell architecture after AAV6 delivery.
Article
Biochemistry & Molecular Biology
Xiaoming Zhu, Kuibao Li, Yuanfeng Gao
Summary: This study found that reducing the expression level of EPHX2 and increasing the level of EET can decrease the activity of presympathetic neurons in the PVN of hypertensive rats, thereby reducing sympathetic activity. In addition, the ATP/SR/D-serine pathway of astrocytes is involved in EET-mediated neuroprotection.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Neurosciences
Preeti Dohare, Muhammad T. Zia, Ehsan Ahmed, Asad Ahmed, Vivek Yadala, Alexandra L. Schober, Juan Alberto Ortega, Robert Kayton, Zoltan Ungvari, Alexander A. Mongin, Praveen Ballabh
JOURNAL OF NEUROSCIENCE
(2016)
Article
Neurosciences
Alexandra L. Schober, Corinne S. Wilson, Alexander A. Mongin
JOURNAL OF PHYSIOLOGY-LONDON
(2017)
Review
Neurosciences
Corinne S. Wilson, Alexander A. Mongin
NEUROSCIENCE LETTERS
(2019)
Article
Oncology
Sebastian Rubino, Martin D. Bach, Alexandra L. Schober, Ian H. Lambert, Alexander A. Mongin
FRONTIERS IN ONCOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Corinne S. Wilson, Martin D. Bach, Zahra Ashkavand, Kenneth R. Norman, Nina Martino, Alejandro P. Adams, Alexander A. Mongin
JOURNAL OF NEUROCHEMISTRY
(2019)
Article
Virology
Jesse Rabinowitz, Hamayun J. Sharifi, Hunter Martin, Anthony Marchese, Michael Robek, Binshan Shi, Alexander A. Mongin, Carlos M. C. de Noronha
Summary: Human macrophages have intrinsic antiviral defenses against HIV-1 infection, with Nrf2 and xCT playing key roles in inhibiting the virus. xCT function impedes infection immediately prior to 2-LTR circle formation.
Article
Biochemistry & Molecular Biology
Corinne S. Wilson, Preeti Dohare, Shaina Orbeta, Julia W. Nalwalk, Yunfei Huang, Russell J. Ferland, Rajan Sah, Annalisa Scimemi, Alexander A. Mongin
Summary: The knockout of the LRRC8A gene in mice leads to seizures in adolescence, as well as abnormalities in neurons and astrocytes in the brain. These abnormalities are associated with reactive astrogliosis, as well as dysregulation of amino acid neurotransmitter uptake and supply by astrocytes.
Editorial Material
Cell Biology
Markus Ritter, Alexander A. Mongin, Giovanna Valenti, Yasunobu Okada
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Editorial Material
Physiology
Alexander A. Mongin
Review
Neurosciences
Alexandra L. Schober, Leigh E. Wicki-Stordeur, Keith K. Murai, Leigh Anne Swayne
Summary: Astrocytes have diverse roles in regulating brain circuit formation and physiology. Recent advancements have revealed a high level of diversity in astrocytes, including molecular, morphological, and functional differences. This diversification begins during embryonic specification events and continues into the early postnatal period, overlapping with synapse development and circuit refinement. There is evidence of molecular crosstalk among astrocytes, neurons, and synapses, suggesting that astrocyte diversity is influenced by and influences this crosstalk. Understanding astrocyte heterogeneity is vital for studying neurological diseases.
TRENDS IN NEUROSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zila Martinez-Lozada, W. Todd Farmer, Alexandra L. Schober, Elizabeth Krizman, Michael B. Robinson, Keith K. Murai
Summary: Astrocytes play essential roles in the health and disease of the central nervous system (CNS). The interactions between astrocytes, neurons, and endothelial cells promote astrocytic maturation. The presence of both neurons and endothelial cells has a greater effect on maturation than either cell alone.
JOURNAL OF NEUROCHEMISTRY
(2023)
Meeting Abstract
Critical Care Medicine
N. O. Dulin, A. A. Mongin, S. Orbeta, E. B. Reed, G. M. Mutlu
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
A. Schober, J. Benjamin Kacerovsky, C. Salmon, N. Alivodej, A. Zhou, B. Phillips, T. Tibuleac, K. Murai
JOURNAL OF NEUROCHEMISTRY
(2019)