Review
Cell Biology
Ana Sofia Coroadinha
Summary: Gene therapy relies on the delivery of genetic material to the patient's cells to provide therapeutic treatment. Lentiviral (LV) and adeno-associated virus (AAV) vectors are two commonly used and efficient delivery systems. However, the therapeutic efficacy of these vectors is hindered by host restriction factors (RFs) that block their transduction. In this review, we discuss the identified RFs that impede LV and AAV vector transduction and limit their therapeutic effectiveness.
Review
Chemistry, Multidisciplinary
Scott M. Stagg, Craig Yoshioka, Omar Davulcu, Michael S. Chapman
Summary: Adeno-associated virus (AAV) is a leading delivery vector in gene therapy treatments. Understanding the structure and molecular interactions of AAV with human hosts is of great interest. Electron microscopic approaches have been used to visualize the virus and its complexes, leading to important findings and new insights.
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
Engineering, Biomedical
Jessie R. Davis, Xiao Wang, Isaac P. Witte, Tony P. Huang, Jonathan M. Levy, Aditya Raguram, Samagya Banskota, Nabil G. Seidah, Kiran Musunuru, David R. Liu
Summary: Compact adenine base editors (ABEs) encoded within size-optimized genomes of adeno-associated viruses (AAVs) enable therapeutic base editing in mice at low doses and high editing efficiencies, simplifying AAV production and characterization.
NATURE BIOMEDICAL ENGINEERING
(2022)
Article
Biotechnology & Applied Microbiology
Michelle Mendiola Pla, Yuting Chiang, Antonio Roki, Chunbo Wang, Franklin H. Lee, Matthew F. Smith, Ryan T. Gross, Jun-Neng Roan, Muath Bishawi, Amy Evans, Lynden E. Gault, Sam Ho, Carolyn Glass, Jacob N. Schroder, Paul Lezberg, Carmelo A. Milano, Dawn E. Bowles
Summary: This study demonstrates the feasibility and efficiency of delivering genes to porcine cardiac allografts utilizing adeno-associated viral vectors during ex vivo perfusion. Durable and dose-dependent transgene expression was achieved in the allografts, supporting the idea of gene therapy interventions to enhance transplantation outcomes.
HUMAN GENE THERAPY
(2023)
Article
Biochemical Research Methods
Logan Thrasher Collins, Selvarangan Ponnazhagan, David T. Curiel
Summary: Gene therapy has the potential to revolutionize disease treatment through direct genetic manipulation of cells. However, the high cost of Adeno-associated virus (AAV) gene therapy limits its accessibility, making it unaffordable for most patients. Therefore, efforts to decrease the production cost of AAVs using synthetic biology design have been proposed to make gene therapy more widely available.
ACS SYNTHETIC BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jalish M. Riyad, Thomas Weber
Summary: Recombinant adeno-associated virus has become the most popular gene therapy vector in the last two decades, with higher doses increasing the risk of adverse events. FDA has recently approved AAV gene therapy for two rare genetic disorders, highlighting the need for better vectors to achieve therapeutic levels with lower doses. The review discusses cellular roadblocks that AAV must overcome and recent advancements in AAV biology that can improve vector performance for safer gene therapy.
Article
Multidisciplinary Sciences
Jianye Fu, Wenwei Han, Xue Zhang, Yutong Sun, Rajendra Bhadane, Bo Wei, Li Li, Liangmin Yu, Jinbo Yang, Jessica M. Rosenholm, Outi M. H. Salo-Ahen, Taojian Fan, Bin Zhang, Wageh Swelm, Ahmed A. Al-Ghamdi, Lin Xia, Han Zhang, Meng Qiu, Hongbo Zhang, Xin Wang
Summary: In this study, amino-modified virus-mimetic spike silica nanoparticles (NH2-SSNs) were developed as efficient delivery vehicles for nucleic acids. These nanoparticles showed excellent delivery performance and biosafety in various cell types and mice. The solid spikes on NH2-SSNs exhibited advantages in storage, transportation, modification, and quality control compared to lipid nanovectors.
Article
Biotechnology & Applied Microbiology
Shantoshini Dash, David M. Sharon, Alaka Mullick, Amine A. Kamen
Summary: This study reveals that only a small proportion of cells are capable of producing measurable levels of assembled AAV capsids despite high transfection efficiencies and nominal vector yields. Increasing the proportion of productive cells could significantly increase vector titer. The flow cytometry assay used in this study may serve as a useful metric for optimizing transfection-based AAV vector manufacturing platforms.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Chemistry, Multidisciplinary
Badri Parshad, Marlena N. Schlecht, Morris Baumgardt, Kai Ludwig, Chuanxiong Nie, Agustina Rimondi, Katja Honzke, Stefano Angioletti-Uberti, Vinod Khatri, Paul Schneider, Andreas Herrmann, Rainer Haag, Andreas C. Hocke, Thorsten Wolff, Sumati Bhatia
Summary: In this study, a low-molecular-weight dual-action linear polymer is used to successfully inhibit different strains of influenza A virus. The optimized polymer targets both hemagglutinin and neuraminidase on the virus surface, leading to effective inhibition of virus propagation. The polymer is significantly more effective than the commercial drug zanamivir, demonstrating its translational potential for broad and high antiviral efficacy.
Article
Surgery
Zhen Cai, Liyuan Zhang, Lixia Zhang, Dongjun Guo
Summary: Transfection of HVEGF(165) gene can enhance the survival of microtia chondrocytes, but does not improve the texture of tissue-engineered cartilage.
AESTHETIC PLASTIC SURGERY
(2022)
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.
Review
Virology
Dunia Asensio-Cob, Javier M. Rodriguez, Daniel Luque
Summary: Rotaviruses are non-enveloped multilayered dsRNA viruses that cause diarrheal disease in humans and animals. The viral particle consists of three protein layers enclosing the segmented dsRNA genome and transcriptional complexes. Each layer is associated with a different phase of the replication cycle, allowing the virus to control its replication by disassembling and assembling its structural proteins. This review examines recent advances in understanding the disassembly and assembly processes of rotavirus particles at the structural, molecular, and cellular levels.
Review
Multidisciplinary Sciences
Rafael Borges Rosa, Emilene Ferreira de Castro, Murilo Vieira da Silva, Denise Caroline Paiva Ferreira, Ana Carolina Gomes Jardim, Igor Andrade Santos, Mikaela dos Santos Marinho, Flavia Batista Ferreira Franca, Lindomar Jose Pena
Summary: The emergence and rapid spread of monkeypox virus (MPXV) outside of endemic areas during the COVID-19 pandemic has created a global health emergency. Scientists have been working on developing in vitro and in vivo models for MPXV research. In vitro models, including 2D and 3D cultures, are cost-effective and can be controlled, but may not fully represent physiological conditions. Therefore, in vivo models are being characterized to meet the demand for studying MPXV. This review summarizes the existing MPXV models and discusses their contributions to understanding pathogenesis, replication, transmission, and antiviral treatment.
Article
Biotechnology & Applied Microbiology
Jinghan Wang, Liping Zhao, Xi Gu, Yuanyuan Xue, Shengyi Wang, Ru Xiao, Luk H. Vandenberghe, Kevin A. Peng, Yilai Shu, Huawei Li
Summary: The study found that AAV can efficiently be delivered into inner ear cells of guinea pigs through the trans-stapes (oval window) route, preserving postoperative hearing. These findings have potential implications for virus-based clinical translation of hearing impairment treatment.
HUMAN GENE THERAPY
(2022)
Article
Medicine, Research & Experimental
Simon M. Petersen-Jones, Laurence M. Occelli, Paige A. Winkler, Winston Lee, Janet R. Sparrow, Mai Tsukikawa, Sanford L. Boye, Vince Chiodo, Jenina E. Capasso, Elvir Becirovic, Christian Schon, Mathias W. Seeliger, Alex V. Levin, Stylianos Michalakis, William W. Hauswirth, Stephen H. Tsang
JOURNAL OF CLINICAL INVESTIGATION
(2018)
Article
Biotechnology & Applied Microbiology
K. Tyler McCullough, Sanford L. Boye, Diego Fajardo, Kaitlyn Calabro, James J. Peterson, Christianne E. Strang, Dibyendu Chakraborty, Sebastian Gloskowski, Scott Haskett, Steven Samuelsson, Haiyan Jiang, C. Douglas Witherspoon, Paul D. Gamlin, Morgan L. Maeder, Shannon E. Boye
HUMAN GENE THERAPY
(2019)
Article
Multidisciplinary Sciences
Omar Akil, Frank Dyka, Charlotte Calvet, Alice Emptoz, Ghizlene Lahlou, Sylvie Nouaille, Jacques Boutet de Monvel, Jean-Pierre Hardelin, William W. Hauswirth, Paul Avan, Christine Petit, Saaid Safieddine, Lawrence R. Lustig
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Neurosciences
Kaitlyn R. Calabro, Sanford L. Boye, Shreyasi Choudhury, Diego Fajardo, James J. Peterson, Wei Li, Sean M. Crosson, Mi-Jung Kim, Dalian Ding, Richard Salvi, Shinichi Someya, Shannon E. Boye
FRONTIERS IN NEUROSCIENCE
(2019)
Article
Neurosciences
Marshall S. Goodwin, Cara L. Croft, Hunter S. Futch, Daniel Ryu, Carolina Ceballos-Diaz, Xuefei Liu, Giavanna Paterno, Catalina Mejia, Doris Deng, Kimberly Menezes, Laura Londono, Kefren Arjona, Mary Parianos, Van Truong, Eva Rostonics, Amanda Hernandez, Sanford L. Boye, Shannon E. Boye, Yona Levites, Pedro E. Cruz, Todd E. Golde
MOLECULAR NEURODEGENERATION
(2020)
Article
Biotechnology & Applied Microbiology
Hyung-Joo Kwon, Keyun Qing, Selvarangan Ponnazhagan, Xu-Shan Wang, David M. Markusic, Siddhant Gupte, Shannon E. Boye, Arun Srivastava
HUMAN GENE THERAPY
(2020)
Article
Biotechnology & Applied Microbiology
Sanford L. Boye, Shreyasi Choudhury, Sean Crosson, Giovanni Di Pasquale, Sandra Afione, Russell Mellen, Victoria Makal, Kaitlyn R. Calabro, Diego Fajardo, James Peterson, Hangning Zhang, Matthew T. Leahy, Colin K. Jennings, John A. Chiorini, Ryan F. Boyd, Shannon E. Boye
Article
Behavioral Sciences
Joel D. Mainland, Linda A. Barlow, Steven D. Munger, Sarah E. Millar, M. Natalia Vergara, Peihua Jiang, James E. Schwob, Bradley J. Goldstein, Shannon E. Boye, Jeffrey R. Martens, Donald A. Leopold, Linda M. Bartoshuk, Richard L. Doty, Thomas Hummel, Jayant M. Pinto, Casey Trimmer, Christine Kelly, Edmund A. Pribitkin, Danielle R. Reed
Article
Biochemistry & Molecular Biology
Janine A. Gilkes, Benjamin L. Judkins, Brontie N. Herrera, Ronald J. Mandel, Sanford L. Boye, Shannon E. Boye, Arun Srivastava, Coy D. Heldermon
Summary: The study evaluated two intracranially administered adeno-associated virus serotype 8 variants for potential treatment of MPS IIIB, with one variant (double Y-F + T-V) showing better efficacy. The IC6 method resulted in the widest biodistribution within the brain, indicating enhanced utility of the capsid modified AAV8 variant for therapeutic purposes.
Review
Biotechnology & Applied Microbiology
Jerry R. Mendell, Samiah A. Al-Zaidy, Louise R. Rodino-Klapac, Kimberly Goodspeed, Steven J. Gray, Christine N. Kay, Sanford L. Boye, Shannon E. Boye, Lindsey A. George, Stephanie Salabarria, Manuela Corti, Barry J. Byrne, Jacques P. Tremblay
Summary: Hereditary diseases are caused by gene mutations, affecting millions of Americans, and gene therapy using adeno-associated virus (AAV) has shown promise in treating these diseases. Five treatments have been approved for commercialization, with many more in clinical trials, showcasing the potential of gene therapy in treating a wide range of genetic disorders.
Article
Virology
Sean M. Crosson, Antonette Bennett, Diego Fajardo, James J. Peterson, Hangning Zhang, Wei Li, Matthew T. Leahy, Colin K. Jennings, Ryan F. Boyd, Sanford L. Boye, Mavis Agbandje-McKenna, Shannon E. Boye
Summary: Rationally designed AAV2-based capsid variants with specific hydrophilic and hydrophobic amino acid mutations can significantly enhance retinal transduction, especially when considering the impact of these mutations on HSPG binding and vector tropism in a clinically relevant animal model.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Samuel G. Jacobson, Artur Cideciyan, Allen C. Ho, Igor Peshenko, Alexandra Garafalo, Alejandro J. Roman, Alexander Sumaroka, Vivian Wu, Arun K. Krishnan, Rebecca Sheplock, Sanford L. Boye, Alexander M. Dizhoor, Shannon E. Boye
Summary: The ongoing first-in-human clinical trial of gene therapy for Leber congenital amaurosis due to mutations in the GUCY2D gene has shown promising early results, demonstrating safety and efficacy in both rod and cone photoreceptor function.
Article
Biotechnology & Applied Microbiology
Xiajie Ma, Emily R. Sechrest, Diego Fajardo, Ping Zhu, Frank Dyka, Yixiao Wang, Ekaterina Lobanova, Shannon E. Boye, Wolfgang Baehr, Wen-Tao Deng
Summary: The study demonstrates that AAV-mediated gene augmentation therapy can rescue cone structure and function in a mouse model with a congenital opsin deletion, emphasizing the importance of early intervention for successful therapy.
HUMAN GENE THERAPY
(2022)
Article
Biology
Yo Sasaki, Hiroki Kakita, Shunsuke Kubota, Abdoulaye Sene, Tae Jun Lee, Norimitsu Ban, Zhenyu Dong, Joseph B. Lin, Sanford L. Boye, Aaron DiAntonio, Shannon E. Boye, Rajendra S. Apte, Jeffrey Milbrandt
Article
Biochemistry & Molecular Biology
Wen-Tao Deng, Jie Li, Ping Zhu, Vince A. Chiodo, W. Clay Smith, Beau Freedman, Wolfgang Baehr, Jijing Pang, William W. Hauswirth