Article
Biotechnology & Applied Microbiology
Shinnosuke Tsuji, Calvin J. Stephens, Giulia Bortolussi, Feijie Zhang, Gabriele Baj, Hagoon Jang, Gustavo de Alencastro, Andres F. Muro, Katja Pekrun, Mark A. Kay
Summary: The use of ribonucleotide reductase inhibitors can substantially enhance the efficiency of adeno-associated virus-mediated homologous recombination-based gene therapy. These findings suggest that clinically approved inhibitors, such as fludarabine, can be used to potentiate gene editing therapies.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yong Tao, Xiaoyi Liu, Liu Yang, Cenfeng Chu, Fangzhi Tan, Zehua Yu, Junzi Ke, Xiang Li, Xiaofei Zheng, Xingle Zhao, Jieyu Qi, Chao-Po Lin, Renjie Chai, Guisheng Zhong, Hao Wu
Summary: The cochlea is composed of multiple types of cells responsible for converting mechanical forces into electric signals for hearing. Gene therapy has shown promise in animal deafness models, and the AAV-ie-K558R mutant is efficient in delivering genes to specific cells in the cochlea, potentially treating hearing loss caused by hair cell death.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Ophthalmology
Michelle E. McClements, Hannah Steward, William Atkin, Emily Archer Goode, Carolina Gandara, Valeria Chichagova, Robert E. MacLaren
Summary: The study aims to improve the efficient transduction of human retinal organoid-like cells for gene therapy treatments, and results show that reliable transduction can be readily achieved with different AAV serotypes.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Amaury Pupo, Audry Fernandez, Siew Hui Low, Achille Francois, Lester Suarez-Amaran, Richard Jude Samulski
Summary: Defective genes account for X80% of known diseases. Gene therapy offers a one-time treatment option for fixing genetic errors. Adeno-associated virus (AAV) vectors are efficient for in vivo gene delivery but face challenges. This review discusses approaches to improve AAV vectors for gene therapy.
Review
Pharmacology & Pharmacy
Cole W. Peters, Casey A. Maguire, Killian S. Hanlon
Summary: Gene therapy is becoming more important in treating genetic diseases, especially Mendelian disorders. The development of new viral vectors has increased the options for treatment. This review provides an overview of gene therapies in the brain, ear, and eye, emphasizing the optimal approaches depending on cell type and transgene.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ahmara G. Ross, Brahim Chaqour, Devin S. McDougald, Kimberly E. Dine, Thu T. Duong, Ryan E. Shindler, Jipeng Yue, Tehui Liu, Kenneth S. Shindler
Summary: This study demonstrates that targeted expression of SIRT1 in retinal ganglion cells (RGCs) using an AAV vector can reduce RGC loss, axon demyelination, and visual deficits associated with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis.
Review
Clinical Neurology
Xue Zhang, Fang Chen, Mingyue Sun, Nan Wu, Bin Liu, Xiangming Yi, Ruli Ge, Xueli Fan
Summary: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease that causes disability in young adults. The damage to myelin, oligodendrocytes, and axons is the characteristic feature of MS. Microglia play important roles in CNS surveillance, neurogenesis, synaptic refinement, and myelin pruning, but their continuous activation can contribute to neurodegeneration.
FRONTIERS IN NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Arjun K. Fontaine, Gregory L. Futia, Pradeep S. Rajendran, Samuel F. Littich, Naoko Mizoguchi, Kalyanam Shivkumar, Jeffrey L. Ardell, Diego Restrepo, John H. Caldwell, Emily A. Gibson, Richard F. ff Weir
Summary: Optogenetic techniques can target neural communication with light-sensitive actuators for organ-specific neuromodulation. Stimulating vagus nerve fibers using photostimulation can induce changes in cardiac function, as demonstrated by alterations in heart rate, electrocardiogram, and respiratory responses. Retrograde labeling shows promise for organ-specific optical neuromodulation.
SCIENTIFIC REPORTS
(2021)
Article
Virology
Zengpeng Han, Nengsong Luo, Fei Wang, Yuxiang Cai, Xin Yang, Weiwei Feng, Zhenxiang Zhu, Jie Wang, Yang Wu, Chaohui Ye, Kunzhang Lin, Fuqiang Xu
Summary: In this study, two novel AAV variants, AAV2.A1 and AAV2.A2, were generated by engineering the VR-IV region of AAV2. The transduction efficiency of these variants in the central nervous system was found to be 10-15 times higher than that of AAV2, providing new vehicles for gene drug delivery to the brain.
Review
Biochemistry & Molecular Biology
Bijay P. Dhungel, Charles G. Bailey, John E. J. Rasko
Summary: With the increasing approval of AAV-based gene therapies for human use, understanding vector-host interactions becomes crucial. Advances in genome-wide genetic screening tools have enabled a clearer picture of AAV-host interactions, providing insights into the viral life cycle and potential novel strategies to overcome current limitations of AAV-based vectors. This summary outlines the current understanding of the stages in the journey of the vector and the roles of recently identified host factors.
TRENDS IN MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Mei Li, Zhuang Liu, Yang Wu, Ning Zheng, Xiaodong Liu, Aoling Cai, Danhao Zheng, Jinpiao Zhu, Jinfeng Wu, Lingling Xu, Xihai Li, Ling-Qiang Zhu, Anne Manyande, Fuqiang Xu, Jie Wang
Summary: This study developed an MRI-based method to monitor astrocytes in live animals, using AAV vectors carrying the GFAP promoter driving the AQP1 fusion gene. The novel AAV mutation increased fluorescence intensity, and the AQP1-carrying AAV induced changes in MRI contrast in cell cultures and brain regions. The study provides a tool to detect dynamic changes in astrocytes in live animals.
MOLECULAR PSYCHIATRY
(2022)
Article
Biotechnology & Applied Microbiology
Dhwanil A. Dalwadi, Laura Torrens, Jordi Abril-Fornaguera, Roser Pinyol, Catherine Willoughby, Jeffrey Posey, Josep M. Llovet, Christian Lanciault, David W. Russell, Markus Grompe, Willscott E. Naugler
Summary: Integration of adeno-associated virus (AAV) into host genomes can lead to hepatocellular carcinoma (HCC), especially when it occurs in oncogenic hotspots. Research has shown that mice exposed to rAAV gene therapy in the context of non-alcoholic fatty liver disease (NAFLD) are more likely to develop HCC, highlighting the potential risk factors associated with rAAV-induced oncogenesis.
Article
Biochemistry & Molecular Biology
Terence R. Flotte, Oguz Cataltepe, Ajit Puri, Ana Rita Batista, Richard Moser, Diane McKenna-Yasek, Catherine Douthwright, Gwladys Gernoux, Meghan Blackwood, Christian Mueller, Phillip W. L. Tai, Xuntian Jiang, Scot Bateman, Spiro G. Spanakis, Julia Parzych, Allison M. Keeler, Aly Abayazeed, Saurabh Rohatgi, Laura Gibson, Robert Finberg, Bruce A. Barton, Zeynep Vardar, Mohammed Salman Shazeeb, Matthew Gounis, Cynthia J. Tifft, Florian S. Eichler, Robert H. Brown, Douglas R. Martin, Heather L. Gray-Edwards, Miguel Sena-Esteves
Summary: This study presents the results of AAV gene therapy in two patients with infantile TSD. The treatment was well tolerated without vector-related adverse events, and demonstrated an increase and stability of HexA activity in the cerebrospinal fluid. One patient showed disease stabilization, while the other experienced disease progression after treatment.
Article
Neurosciences
Chidera C. Alim, Christopher Y. Ko, Juliana Mira Hernandez, Erin Y. Shen, Sonya Baidar, Ye Chen-Izu, Donald M. Bers, Julie Bossuyt
Summary: Cardiac mechanical afterload induces autoregulatory increase in myocyte Ca2+ dynamics and contractility, and this process is regulated by calcium/calmodulin-dependent protein kinase II (CaMKII) and nitric oxide (NO).
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Biochemistry & Molecular Biology
Xiufang Pan, Yongping Yue, Maria Boftsi, Lakmini P. Wasala, Ngoc Tam Tran, Keqing Zhang, David J. Pintel, Phillip W. L. Tai, Dongsheng Duan
Summary: The study found that complete elimination of CpG motifs in the ITR does not impact the biological activity of the AAV vector. CpG-free ITRs could be valuable in engineering therapeutic AAV vectors.
Article
Neurosciences
Edmund R. Hollis, Nao Ishiko, Kristine Tolentino, Ernest Doherty, Maria J. Rodriguez, Nigel A. Calcutt, Yimin Zou
EXPERIMENTAL NEUROLOGY
(2015)
Review
Clinical Neurology
Edmund R. Hollis
Article
Multidisciplinary Sciences
Edmund R. Hollis, Nao Ishiko, Maysam Pessian, Kristine Tolentino, Corinne A. Lee-Kubli, Nigel A. Calcutt, Yimin Zou
NATURE COMMUNICATIONS
(2015)
Article
Neurosciences
Edmund R. Hollis, Nao Ishiko, Ting Yu, Chin-Chun Lu, Ariela Haimovich, Kristine Tolentino, Alisha Richman, Anna Tury, Shih-Hsiu Wang, Maysam Pessian, Euna Jo, Alex Kolodkin, Yimin Zou
NATURE NEUROSCIENCE
(2016)
Editorial Material
Cell Biology
Yue Li, Edmund R. Hollis
NEURAL REGENERATION RESEARCH
(2017)
Review
Neurosciences
Najet Serradj, Sydney F. Agger, Edmund R. Hollis
NEUROSCIENCE LETTERS
(2017)
Review
Clinical Neurology
Hisham Mohammed, Edmund R. Hollis
Review
Neurosciences
Keisuke Onishi, Edmund Hollis, Yimin Zou
CURRENT OPINION IN NEUROBIOLOGY
(2014)
Review
Clinical Neurology
Edmund R. Hollis, Mark H. Tuszynski
Article
Multidisciplinary Sciences
Edmund R. Hollis, Yimin Zou
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2012)
Article
Cell Biology
Roman J. Giger, Edmund R. Hollis, Mark H. Tuszynski
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2010)
Article
Neurosciences
Edmund R. Hollis, Yimin Zou
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2012)
Article
Neurosciences
Yue Li, Edmund Hollis
Summary: Motor control relies on precise encoding and modulation across various motor centers, refined through learning repetition. The baso-cortical cholinergic pathway plays a critical role in the acquisition of coordinated motor skills in mice, with depletion of cholinergic neurons leading to significant impairments in training. Cholinergic neuromodulation during training is essential for task acquisition, specifically influencing corticostriatal neurons in the prefrontal and motor cortex.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Najet Serradj, Francesca Marino, Yunuen Moreno-Lopez, Amanda Bernstein, Sydney Agger, Marwa Soliman, Andrew Sloan, Edmund Hollis
Summary: Corticospinal neuron activity plays a crucial role in the learning and execution of precise motor movements in mice. The temporal coding of corticospinal activity is found to be associated with the development of precise prehension movements. Transection of the corticospinal tract and optogenetic regulation of corticospinal activity further confirm the necessity of corticospinal network modulation in precise movements.
NATURE COMMUNICATIONS
(2023)