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)
Review
Virology
Amir Asri Kojabad, Mahdieh Farzanehpour, Hadi Esmaeili Gouvarchin Galeh, Ruhollah Dorostkar, Ali Jafarpour, Masoumeh Bolandian, Majid Mirzaei Nodooshan
Summary: ddPCR is a high-throughput digital PCR method that offers high sensitivity, specificity, absolute quantification without the need for a standard curve, good reproducibility, and tolerance to PCR inhibitors, making it a valuable addition to virologists' toolbox. Recent technological advances in ddPCR methods and their applications in viral identification are outlined in this review.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Review
Clinical Neurology
Robert Duba-Kiss, Yosuke Niibori, David R. Hampson
Summary: This Mini Review discusses the use of various gene regulatory elements for targeting GABAergic neurons, with a focus on adeno-associated viral vectors, the most widely used class of viral vectors for treating brain diseases.
FRONTIERS IN NEUROLOGY
(2021)
Article
Medicine, Research & Experimental
Kelsey R. Pflepsen, Cristina D. Peterson, Kelley F. Kitto, Maureen S. Riedl, R. Scott McIvor, George L. Wilcox, Lucy Vulchanova, Carolyn A. Fairbanks
Summary: The distribution and kinetics of AAV5 vector following lumbar intrathecal injection in mice were evaluated in this study. Results showed rapid distribution of AAV5 particles to all levels of the spinal cord and dorsal root ganglia, with preferential targeting of DRG tissue and possible clearance mechanisms via DRG macrophages.
MOLECULAR PHARMACEUTICS
(2021)
Article
Virology
Xiuyu Lou, Hao Yan, Lingxuan Su, Yi Sun, Xinyin Wang, Liming Gong, Yin Chen, Zhen Li, Zhongbiao Fang, Haiyan Mao, Keda Chen, Yanjun Zhang
Summary: A RT-dd PCR method was developed to detect the R294K mutation in H7N9 and successfully detected 2 R294K mutations in clinical samples. The sensitivity and specificity of RT-dd PCR were similar to RT-qPCR, and the accuracy was comparable to NGS.
Article
Nanoscience & Nanotechnology
Miguel R. Chuapoco, Nicholas C. Flytzanis, Nick Goeden, J. Christopher Octeau, Kristina M. Roxas, Ken Y. Chan, Jon Scherrer, Janet Winchester, Roy J. Blackburn, Lillian J. Campos, Kwun Nok Mimi Man, Junqing Sun, Xinhong Chen, Arthur Lefevre, Vikram Pal Singh, Cynthia M. Arokiaraj, Timothy F. Shay, Julia Vendemiatti, Min J. Jang, John K. Mich, Yemeserach Bishaw, Bryan B. Gore, Victoria Omstead, Naz Taskin, Natalie Weed, Boaz P. Levi, Jonathan T. Ting, Cory T. Miller, Benjamin E. Deverman, James Pickel, Lin Tian, Andrew S. Fox, Viviana Gradinaru
Summary: Crossing the blood-brain barrier in primates is a major challenge for gene delivery. Researchers have identified an engineered variant, AAV.CAP-Mac, which efficiently delivers genes to the brains of multiple non-human primate species, potentially enabling non-invasive systemic gene transfer.
NATURE NANOTECHNOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Hanna J. Wagner, Wilfried Weber, Martin Fussenegger
Summary: The recent approvals and ongoing clinical trials have established adeno-associated virus (AAV) as the leading gene delivery vehicle in gene therapy. Pharmaceutical companies are investing in AAV to expand therapeutic options. The emerging field of synthetic-biologically engineered AAV vectors has great potential to shape future gene therapeutic approaches.
Article
Chemistry, Physical
Yuanyuan Wei, Syed Muhammad Tariq Abbasi, Nawaz Mehmood, Luoquan Li, Fuyang Qu, Guangyao Cheng, Dehua Hu, Yi-Ping Ho, Wu Yuan, Ho-Pui Ho
Summary: The study presents a deep learning-aided algorithm called Deep-qGFP for real-time absolute quantification. It enables automated detection and classification of fluorescent-labeled microreactors, accurately measuring their sizes and occupancy status. Deep-qGFP achieves high accuracy and remarkable speed, making it applicable to various GFP-labeling scenarios. It can be seamlessly integrated into common fluorescence microscopes and different microreactor formats, optimizing laboratory practices and potentially transforming GFP-labeled microreactor analysis.
Article
Medicine, Research & Experimental
Ling Li, Chianru Tan, Jia Zeng, Chen Luo, Shi Hu, Yanke Peng, Wenjuan Li, Zhixiong Xie, Yueming Ling, Xuejun Zhang, E. Deng, Haixia Xu, Jue Wang, Yudi Xie, Yaling Zhou, Wei Zhang, Yong Guo, Zhong Liu
Summary: This study collected nasopharyngeal swabs, anal swabs, saliva, blood, and urine specimens from patients with a course of disease ranging from 7 to 69 days. It was found that the positive detection rate was highest in nasopharyngeal swabs, followed by anal swabs. There was no significant correlation between antibody levels and days after symptom onset or viral load.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Chemistry, Analytical
Liao Chen, Vivek Yadav, Chenguang Zhang, Xiaoye Huo, Ceming Wang, Satyajyoti Senapati, Hsueh-Chia Chang
Summary: The droplet digital PCR (ddPCR) platform reported in this study utilizes a unique flattened pipette tip design to achieve rapid, stable, and highly sensitive quantification of low virus RNA load without the need for bulky lab-bound equipment. The technology allows for fast generation of thousands of monodispersed droplets, which can be easily counted or imaged for accurate quantification of target copies. This platform shows promising potential for rapid virus detection and epidemic control, offering a convenient solution for point-of-care (POC) applications.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Melad Farraha, Renuka Rao, Sindhu Igoor, Thi Y. L. Le, Michael A. Barry, Christopher Davey, Cindy Kok, James J. H. Chong, Eddy Kizana
Summary: This study aimed to develop a biological alternative to electronic pacemakers by using gene therapy to convert cardiomyocytes into sinoatrial node-like cells. The results showed that the transduction of hTBX18 gene resulted in morphological, molecular, physiological, and functional changes in the cardiomyocytes, recapitulating the pacemaker phenotype. The use of a clinically relevant vector opens new prospects for the development of biological pacemakers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yung-An Huang, Jeng-Chang Chen, Chih-Ching Wu, Chia-Wei Hsu, Albert Min-Shan Ko, Li-Chen Chen, Ming-Ling Kuo
Summary: The study demonstrated that applying rAAV-CD39 to asthmatic mice can reduce lung eATP levels and alleviate asthma symptoms, including decreased airway hyperresponsiveness, eosinophilia, mucin deposition, and IL-5/IL-13 production. Additionally, the treatment led to reduced IL-5/IL-13 production and increased frequency of CD4(+)FoxP3(+) regulatory T cells in draining lymph nodes, indicating potential therapeutic benefits of rAAV-CD39 for asthma.
Article
Medicine, Research & Experimental
Alexandra M. Burr, Pamela Cabahug Zuckerman, Alesha B. Castillo, Nicola C. Partridge, Biju Parekkadan
Summary: This study investigates the feasibility of delivering full-length PTH using AAV vectors. The results show the ability to secrete full-length PTH from various cell types in vitro and demonstrate the bioactivity of PTH in inducing proliferation in osteosarcoma cell lines. In vivo experiments also show increased liver and plasma concentrations of PTH, as well as dose-dependent changes in tumor growth and blood biomarkers. This proof-of-concept study suggests the potential of AAV gene therapy for hypoparathyroidism.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Chemistry, Analytical
Rui Wang, Ying Liu, Shuaiwei Chen, Linlin Bai, Kaiming Guo, Yanan Pang, Feng Qian, Yongfang Li, Li Ding, Yongming Wang
Summary: Bloodstream infection is a global health problem with high mortality. This study proposes a novel strategy called utPCR that combines the sensitivity of digital PCR with a shortened reaction time, enabling single-molecule detection. The utPCR shows promising applications in the next generation of molecular diagnosis.
Article
Biochemistry & Molecular Biology
Wataru Aiba, Takamitsu Amai, Mitsuyoshi Ueda, Kouichi Kuroda
Summary: This study successfully increased the efficiency of precise genome editing by creating a donor DNA/guide RNA hybrid duplex. Compared to editing with separately introduced gRNA and donor DNA, the HDR-mediated editing efficiency using this hybrid duplex technique was improved by 1.8-fold.
Article
Biotechnology & Applied Microbiology
Jenny A. Greig, Melanie K. Smith, Jayme M. L. Nordin, Tamara Goode, Edward A. Chroscinski, Elizabeth L. Buza, Nicole Schmidt, Lisa M. Kattenhorn, Samuel Wadsworth, James M. Wilson
Summary: In a study on hemophilia A mouse model, the minimally effective dose (MED) of gene therapy vector was determined to be 3 x 10(11) GC/kg. Total bilirubin levels increased with higher vector doses, while no significant differences were observed in liver transaminase levels. There were no vector-related gross or histological findings detected.
HUMAN GENE THERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Makoto Horiuchi, Christian J. J. Hinderer, Hailey N. N. Shankle, Peter M. M. Hayashi, Jessica A. A. Chichester, Casey Kissel, Peter Bell, Cecilia Dyer, James M. M. Wilson
Summary: Advancements in AAV-based gene therapy hold significant potential for treating rare genetic disorders and addressing unmet medical needs. However, the presence of anti-AAV neutralizing antibodies (NAbs) in human populations limits the efficacy of these therapies. By using FcRn-inhibiting monoclonal antibodies, such as M281, pre-existing NAbs can be reduced, allowing for enhanced gene delivery in NAb-positive patients. This study highlights the importance of mitigating humoral immunity to make AAV-based gene therapies effective.
HUMAN GENE THERAPY
(2023)
Article
Immunology
Juliette Hordeaux, Ali Ramezani, Steve Tuske, Nickita Mehta, Chunjuan Song, Anna Lynch, Katherine Lupino, Jessica A. Chichester, Elizabeth L. Buza, Cecilia Dyer, Hongwei Yu, Peter Bell, Jill M. Weimer, Hung Do, James M. Wilson
Summary: Immune responses to human non-self transgenes in adeno-associated virus (AAV) gene therapy candidates in nonhuman primates can be challenging. A gene therapy candidate for Pompe disease consisting of AAVhu68 was developed, and some severe adaptive immune responses to the therapy were observed, with variability between animals. Cardiac toxicity was found to be associated with a specific haplotype, and an immunodominant peptide was identified as a potential cause. Additionally, robust and safe gene transfer was achieved in an animal with low pre-existing neutralizing antibodies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Jenny A. Greig, Joanna K. Chorazeczewski, Vivek Chowdhary, Melanie K. Smith, Matthew Jennis, James C. Tarrant, Elizabeth L. Buza, Kimberly Coughlan, Paolo G. V. Martini, James M. Wilson
Summary: Crigler-Najjar syndrome is a rare disorder characterized by hyperbilirubinemia and jaundice caused by UGT1A1 mutations. This study investigated the therapeutic potential of lipid nanoparticle-encapsulated hUGT1A1 mRNA therapy in a mouse model and demonstrated that it can effectively reduce bilirubin levels. The results suggest that this treatment modality may be a potential option for Crigler-Najjar syndrome.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Veterinary Sciences
Shelly L. Vaden, Allison R. Kendall, Jonathan D. Foster, Heidi L. New, Jane S. Eagleson, Jacky L. May, Anne M. Traas, Matthew J. Wilson, Beth H. Mcintyre, Christian J. Hinderer, Lauren K. Olenick, James M. Wilson
Summary: The study suggests that SB-001 therapy can effectively treat nonregenerative anemia in cats with CKD, and it is generally well tolerated. However, some cats experienced side effects of hypertension and encephalopathy during the treatment.
JOURNAL OF VETERINARY INTERNAL MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Jenny A. Greig, Kelly M. Martins, Camilo Breton, R. Jason Lamontagne, Yanqing Zhu, Zhenning He, John White, Jing-Xu Zhu, Jessica A. Chichester, Qi Zheng, Zhe Zhang, Peter Bell, Lili Wang, James M. Wilson
Summary: Through studying nonhuman primates, we discovered limitations in gene therapy for the liver due to the mechanism of transduction affecting performance. Although transgene expression declines and stabilizes over time, high transduction of non-immunogenic transgenes is still possible. AAV-mediated transgene expression in primate hepatocytes occurs in two phases: high but short-lived expression from episomal genomes, followed by lower but stable expression from integrated vectors.
NATURE BIOTECHNOLOGY
(2023)
Article
Biology
Teerapat Rojsajjakul, Juliette J. Hordeaux, Gourav R. Choudhury, Christian J. Hinderer, Clementina Mesaros, James M. Wilson, Ian A. Blair
Summary: Deficiency in human mature frataxin protein leads to Friedreich's ataxia. Gene therapy, specifically increasing the expression of heart frataxin protein, offers a potential way to prevent early mortality in patients. Using rhesus macaques, researchers tested the pharmacology of a gene therapy treatment and successfully developed a species-specific quantitative method to analyze protein expression in monkey heart tissue.
COMMUNICATIONS BIOLOGY
(2023)
Meeting Abstract
Biotechnology & Applied Microbiology
Eileen Workman, Mariya Kostiv, Julia Johansson, Christian Hinderer, James M. Wilson
Meeting Abstract
Biotechnology & Applied Microbiology
Eileen Workman, Mariya Kostiv, Julia Johansson, Christian Hinderer, James M. Wilson
Meeting Abstract
Biotechnology & Applied Microbiology
Nerea Zabaleta, Urja Bhatt, Cecile Herate, Pauline Maisonnasse, Jessica A. Chichester, Julio Sanmiguel, Cheikh Diop, James M. Wilson, Roger Le Grand, Luk H. Vandenberghe
Meeting Abstract
Biotechnology & Applied Microbiology
Gourav R. Choudhury, Juliette Hordeaux, Christopher Petucci, Brianne Jeffrey, Melissa White, Tamara Goode, Hongwei Yu, Peter Bell, James M. Wilson
Meeting Abstract
Biotechnology & Applied Microbiology
Christian Hinderer, Rod Miller, Cecilia Dyer, Isaac Chen, Elizabeth Buza, Fe Wright, Phil Latourette, James M. Wilson
Meeting Abstract
Biotechnology & Applied Microbiology
Juliette Hordeaux, Lane H. Wilson, Elizabeth L. Buza, Casey L. Kissel, Nicole Maertzig, Cecilia D. Dyer, James M. Wilson
Meeting Abstract
Biotechnology & Applied Microbiology
Juliette Hordeaux, Chunjuan Song, Tobias Willer, Yanchun Li, Pai-Chi Tsai, Daniel Ellsworth, Peter Bell, Hongwei Yu, Monika Mittal, Jill Weimer, Hung Do, James M. Wilson
Meeting Abstract
Biotechnology & Applied Microbiology
Richard J. Lamontagne, Rucha Fadnavis, Anne Mentzinger, Jenny A. Greig, James M. Wilson