Article
Pharmacology & Pharmacy
Yu (Zoe) Zhang, Roberto A. DePaz, Jared S. Bee, Tristan Marshall
Summary: The study developed a lyophilized AAV formulation that maintained stability for 24 months, showcasing the feasibility of a dried formulation for AAV gene therapy. By optimizing the composition and residual moisture range, as well as utilizing sucrose, citrate, and glycerol, AAV8 was protected from degradation and potency loss.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Biology
Yukihiro Okada, Nobutake Hosoi, Yasunori Matsuzaki, Yuuki Fukai, Akito Hiraga, Junichi Nakai, Keisuke Nitta, Yoichiro Shinohara, Ayumu Konno, Hirokazu Hirai
Summary: Microglia-targeting AAV vectors containing a 1.7-kb putative promoter region of microglia/macrophage-specific Iba1, along with repeated miRNA target sites for miR-9 and miR-129-2-3p, were successfully used to transduce microglia in mice and monitor microglial motility and intracellular Ca2+ mobilization. This study provides valuable tools for studying microglial pathophysiology and therapies in the striatum and cerebellum.
COMMUNICATIONS BIOLOGY
(2022)
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
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
Hyeck-Soo Son, Albert. S. S. Jun, James. W. W. Foster, Wei Wang, Yassine Daoud, Gerd. U. U. Auffarth, Madhuparna Roy
Summary: This study evaluates the efficacy of in situ AAV-mediated gene delivery into the human corneal limbal region via targeted sub-limbal injection technique. The results demonstrate the feasibility and efficiency of the sub-limbal injection technique in specifically targeting cells in the human limbus. This technique may provide a feasible mode of genetic therapy for corneal disorders with an epithelial etiology.
SCIENTIFIC REPORTS
(2022)
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)
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)
Review
Chemistry, Medicinal
Zachary J. Tickner, Michael Farzan
Summary: Riboswitches offer advantages for regulating AAV-delivered gene therapy due to their small genomic footprints and non-immunogenicity. Their ligand-sensing aptamer domains can be exchanged for diverse regulation. Recent screening methods allow rapid isolation of high-performing riboswitches.
Review
Biochemistry & Molecular Biology
Leyao Li, Lakshmy Vasan, Bryan Kartono, Kevan Clifford, Ahmadreza Attarpour, Raghav Sharma, Matthew Mandrozos, Ain Kim, Wenda Zhao, Ari Belotserkovsky, Claire Verkuyl, Gerold Schmitt-Ulms
Summary: This review introduces the use of recombinant adeno-associated virus (rAAV) vectors in the treatment of neurodegenerative diseases, highlighting recent research advancements and challenges. It provides a reference for newcomers to the field and directs researchers struggling to keep up with the literature towards important studies. The review covers early milestones, current clinical trials, gene editing applications, and payload elements of rAAV vectors, as well as discusses the risks and mitigation strategies associated with off-target effects and immunogenicity.
Review
Chemistry, Multidisciplinary
Gregg A. Duncan
Summary: One of the key challenges in gene therapy is to overcome pre-existing and therapy-induced immune responses, as well as to enhance the distribution and activity of AAV in target tissues. Interdisciplinary approaches may help overcome these obstacles and create new opportunities for precision gene therapy.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Engineering, Chemical
Brian Ladd, Kevin Bowes, Mats Lundgren, Torbjorn Graslund, Veronique Chotteau
Summary: This study investigated the use of microcarrier cultures in a stirred-tank bioreactor for the production of AAV vectors and developed a continuous process based on microcarriers and a stirred-tank bioreactor.
Article
Biotechnology & Applied Microbiology
Ngoc Tam Tran, Emilie Lecomte, Sylvie Saleun, Suk Namkung, Cecile Robin, Kristina Weber, Eric Devine, Veronique Blouin, Oumeya Adjali, Eduard Ayuso, Guangping Gao, Magalie Penaud-Budloo, Phillip W. L. Tai
Summary: Over the past two decades, significant progress has been made in the manufacturing of adeno-associated virus (AAV) vectors to meet the production demands for preclinical and clinical trials. However, the presence of empty AAV capsids and particles containing inaccurate vector genomes remains a concern. Different methods have been utilized to separate empty capsids from full particles, but no single technique can completely eliminate empty or partial capsids. This study reveals that vectors produced by different manufacturing systems exhibit varying degrees of truncated and unresolved species, and purified empty particles actually contain genomes composed of a single truncated and/or unresolved inverted terminal repeat (ITR). These findings provide valuable insights into the efficacy, safety, and quantification of clinical vectors.
HUMAN GENE THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Daniel Stone, Martine Aubert, Keith R. Jerome
Summary: More than 15 years after the first observation of hepatotoxicity following AAV vector administration, recent reports have highlighted the potential impact of AAV-associated neurotoxicity. Both pre-clinical studies and clinical trials have shown neurotoxicity in peripheral nerve ganglia, spinal cord, and direct brain injection. Neurotoxic events vary across species and may be underdiagnosed. This review discusses animal models, causes, consequences, and approaches to mitigate AAV-associated neurotoxicity.
Review
Neurosciences
Jing Wang, Mengna Zhu, Jingyi Sun, Lina Feng, Mingfeng Yang, Baoliang Sun, Leilei Mao
Summary: Stroke is associated with devastating clinical outcomes, and current treatment strategies are largely ineffective. Gene therapy using adeno-associated viruses (AAVs) as gene vectors has emerged as a promising approach for treating central nervous system diseases. This review provides an overview of the biological characteristics of AAV vectors and therapeutic advancements in preclinical models of ischemic stroke. It further investigates the potential of manipulating AAV vectors in preclinical applications, emphasizing the challenges and prospects in viral vector selection, drug delivery strategies, immune reactions, and clinical translation.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
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
Biochemical Research Methods
Sebastian Lange, Thomas Engleitner, Sebastian Mueller, Roman Maresch, Maximilian Zwiebel, Laura Gonzalez-Silva, Guenter Schneider, Ruby Banerjee, Fengtang Yang, George S. Vassiliou, Mathias J. Friedrich, Dieter Saur, Ignacio Varela, Roland Rad
Article
Biotechnology & Applied Microbiology
Sandra Louzada, Walid Algady, Eleanor Weyell, Luciana W. Zuccherato, Paulina Brajer, Faisal Almalki, Marilia O. Scliar, Michel S. Naslavsky, Guilherme L. Yamamoto, Yeda A. O. Duarte, Maria Rita Passos-Bueno, Mayana Zatz, Fengtang Yang, Edward J. Hollox
Article
Biochemistry & Molecular Biology
Mohamed A. Almarri, Anders Bergstrom, Javier Prado-Martinez, Fengtang Yang, Beiyuan Fu, Alistair S. Dunham, Yuan Chen, Matthew E. Hurles, Chris Tyler-Smith, Yali Xue
Article
Neurosciences
Alexandria Beland-Millar, Masaki Takimoto, Taku Hamada, Claude Messier
Article
Biochemistry & Molecular Biology
Sabine Lutz-Bonengel, Harald Niederstaetter, Jana Naue, Rafal Koziel, Fengtang Yang, Timo Saenger, Gabriela Huber, Cordula Berger, Rene Pflugradt, Christina Strobl, Catarina Xavier, Marianne Volleth, Sandra Carina Weiss, Jodi A. Irwin, Erica L. Romsos, Peter M. Vallone, Gudrun Ratzinger, Matthias Schmuth, Pidder Jansen-Duerr, Thomas Liehr, Peter Lichter, Thomas J. Parsons, Stefan Pollak, Walther Parson
Summary: The study identified individuals in a family pedigree with maternal inheritance of mtDNA, where some tissues had repetitive complete mitochondrial genomes Mega-NUMTs, while hair shaft mtDNA sequencing was able to exclude the interference of NUMTs.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Nicola A. Thompson, Marco Ranzani, Louise van der Weyden, Vivek Iyer, Victoria Offord, Alastair Droop, Fiona Behan, Emanuel Goncalves, Anneliese Speak, Francesco Iorio, James Hewinson, Victoria Harle, Holly Robertson, Elizabeth Anderson, Beiyuan Fu, Fengtang Yang, Guido Zagnoli-Vieira, Phil Chapman, Martin Del Castillo Velasco-Herrera, Mathew J. Garnett, Stephen P. Jackson, David J. Adams
Summary: Genetic redundancy plays a crucial role in cell survival and tumor adaptation. The study reveals the impact of FAM50A/FAM50B paralogues on cellular fitness across multiple cell lines, shedding new light on the fitness effects of cancer cells.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Gabriele Picco, Chiara M. Cattaneo, Esmee J. van Vliet, Giovanni Crisafulli, Giuseppe Rospo, Sarah Consonni, Sara F. Vieira, Inigo Sanchez Rodriguez, Carlotta Cancelliere, Ruby Banerjee, Luuk J. Schipper, Daniele Oddo, Krijn K. Dijkstra, Jindrich Cinatl, Martin Michaelis, Fengtang Yang, Federica Di Nicolantonio, Andrea Sartore-Bianchi, Salvatore Siena, Sabrina Arena, Emile E. Voest, Alberto Bardelli, Mathew J. Garnett
Summary: For patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer, targeted therapy and chemotherapy have limited effectiveness due to resistance and toxicities, but the majority of patients still exhibit dependency on WRN, making it a promising therapeutic target.
Article
Multidisciplinary Sciences
Natalia Karina Nascimento da Silva, Cleusa Yoshiko Nagamachi, Luis Reginaldo Ribeiro Rodrigues, Patricia Caroline Mary O'Brien, Fengtang Yang, Malcolm Andrew Ferguson-Smith, Julio Cesar Pieczarka
Summary: This study used integrative analysis of morphological, molecular, and chromosomal data, including chromosomal painting, to investigate the phylogenetics of three species of Lophostoma. The research revealed the phylogenetic relationships within the genus, as well as the monophyly of the subfamily Phyllostominae and the paraphyly of the genus Lophostoma.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Kai Ye, Xi Liu, Danping Li, Lili Gao, Kang Zheng, Jicheng Qu, Nianhong Xing, Fengtang Yang, Baohua Liu, Ao Li, Qiuxiang Pang
Summary: This study cloned 5 MMP genes from Dugesia japonica, and found that DjMMPA is associated with regeneration, maintenance and destruction of neoblast cells. Loss of DjMMPA leads to neoblasts proliferation disorder and eventual death. Knockdown of DjMMPA also impairs regeneration and affects cell differentiation, particularly in ectoderm, possibly by inhibiting Wnt signaling.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Ecology
Melquizedec Luiz Silva Pinheiro, Cleusa Yoshiko Nagamachi, Talita Fernanda Augusto Ribas, Cristovam Guerreiro Diniz, Patricia Caroline Mary O'Brien, Malcolm Andrew Ferguson-Smith, Fengtang Yang, Julio Cesar Pieczarka
Summary: The sandpiper species Actitis macularius has a diploid number of 92, mainly consisting of telocentric pairs, which is higher than the proposed 80 for the avian ancestral karyotype. Fission rearrangements have likely led to the formation of smaller macrochromosomes and microchromosomes in this species. Fluorescence in situ hybridization using Burhinus oedicnemus whole chromosome probes confirmed fissions in specific pairs of macrochromosomes.
BMC ECOLOGY AND EVOLUTION
(2021)
Article
Ecology
Talita Fernanda Augusto Ribas, Julio Cesar Pieczarka, Darren K. Griffin, Lucas G. Kiazim, Cleusa Yoshiko Nagamachi, Patricia Caroline Mary O' Brien, Malcolm Andrew Ferguson-Smith, Fengtang Yang, Alexandre Aleixo, Rebecca E. O'Connor
Summary: Thamnophilidae birds are a diverse group of insectivorous Passeriformes with 225 species and 45 genera, mainly found in lowlands and lower montane forests of Neotropics. Despite the large degree of diversity, only a few species have been karyotyped. Recent studies have shown the occurrence of intrachromosomal rearrangements in birds, which may contribute to speciation events.
BMC ECOLOGY AND EVOLUTION
(2021)
Correction
Biotechnology & Applied Microbiology
Imran Noorani, Jorge de la Rosa, Yoon Ha Choi, Alexander Strong, Hannes Ponstingl, M. S. Vijayabaskar, Jusung Lee, Eunmin Lee, Angela Richard-Londt, Mathias Friedrich, Federica Furlanetto, Rocio Fuente, Ruby Banerjee, Fengtang Yang, Frances Law, Colin Watts, Roland Rad, George Vassiliou, Jong Kyoung Kim, Thomas Santarius, Sebastian Brandner, Allan Bradley
Article
Biotechnology & Applied Microbiology
Imran Noorani, Jorge de la Rosa, Yoonha Choi, Alexander Strong, Hannes Ponstingl, M. S. Vijayabaskar, Jusung Lee, Eunmin Lee, Angela Richard-Londt, Mathias Friedrich, Federica Furlanetto, Rocio Fuente, Ruby Banerjee, Fengtang Yang, Frances Law, Colin Watts, Roland Rad, George Vassiliou, Jong Kyoung Kim, Thomas Santarius, Sebastian Brandner, Allan Bradley
Article
Biotechnology & Applied Microbiology
Wentao Shi, Andrea Massaia, Sandra Louzada, Juliet Handsaker, William Chow, Shane McCarthy, Joanna Collins, Pille Hallast, Kerstin Howe, Deanna M. Church, Fengtang Yang, Yali Xue, Chris Tyler-Smith
Article
Biotechnology & Applied Microbiology
Emanuel Goncalves, Fiona M. Behan, Sandra Louzada, Damien Arnol, Euan A. Stronach, Fengtang Yang, Kosuke Yusa, Oliver Stegle, Francesco Iorio, Mathew J. Garnett