Article
Medicine, General & Internal
D. B. Kohn, C. Booth, K. L. Shaw, J. Xu-Bayford, E. Garabedian, V. Trevisan, D. A. Carbonaro-Sarracino, K. Soni, D. Terrazas, K. Snell, A. Ikeda, D. Leon-Rico, T. B. Moore, K. F. Buckland, A. J. Shah, K. C. Gilmour, S. De Oliveira, C. Rivat, G. M. Crooks, N. Izotova, J. Tse, S. Adams, S. Shupien, H. Ricketts, A. Davila, C. Uzowuru, A. Icreverzi, P. Barman, B. Campo Fernandez, R. P. Hollis, M. Coronel, A. Yu, K. M. Chun, C. E. Casas, R. Zhang, S. Arduini, F. Lynn, M. Kudari, A. Spezzi, M. Zahn, R. Heimke, I. Labik, R. Parrott, R. H. Buckley, L. Reeves, K. Cornetta, R. Sokolic, M. Hershfield, M. Schmidt, F. Candotti, H. L. Malech, A. J. Thrasher, H. B. Gaspar
Summary: Gene therapy for ADA deficiency in 50 patients in the United States and the United Kingdom resulted in high overall survival and event-free survival rates, sustained metabolic correction, and functional immune reconstitution. No adverse events such as replication-competent virus, abnormal proliferations, autoimmunity, or graft-versus-host disease were observed.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Tarun K. Garg, Sarita Garg, Isabelle R. Miousse, Stephen Y. Wise, Alana D. Carpenter, Oluseyi O. Fatanmi, Frits van Rhee, Vijay K. Singh, Martin Hauer-Jensen
Summary: Radiation exposure causes acute damage to hematopoietic and immune cells. A study on nonhuman primates has shown that GT3 can accelerate hematopoietic recovery and aid in the recovery of circulating neutrophils and platelets, suggesting its potential as a medical countermeasure for radiation-induced injury to the hematopoietic system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Anna Lieske, Teng Cheong Ha, Axel Schambach, Tobias Maetzig
Summary: This study developed a multiplexing system for parallel characterization of multiple HSC samples and optimized vector design and gene transfer protocols to demonstrate its applicability in functional characterization of two highly similar HSC populations in a reduced number of mice. The results showed the importance of EPCR for long-term repopulating HSCs and the efficiency of the optimized FGB-driven multiplexing approach for blood cell population characterization in biomedical research.
HUMAN GENE THERAPY
(2021)
Review
Multidisciplinary Sciences
Mei Huang, Jiao Yang, Peng Li, Yongchang Chen
Summary: Nonhuman primate models play an increasingly indispensable role in translational medicine research, with unique advantages in mimicking clinical patients, although there is still a remaining gap between basic research of NHP models and translational medicine.
Review
Biotechnology & Applied Microbiology
Tolulope O. Rosanwo, Daniel E. Bauer
Summary: Genome editing in somatic cells offers new therapeutic possibilities for sickle cell disease and β-thalassemia, leveraging clinical knowledge of stem cell transplant and gene transfer. Despite exciting progress, optimization in gene modification efficiency, specificity, delivery to stem cells, and engraftment remains necessary for ideal clinical implementation. This approach highlights the potential of genome editing as a novel treatment for common monogenic disorders and the challenges in clinical implementation.
Article
Cell Biology
C. J. Little, W. J. Haynes, L. Huang, C. M. Daffada, K. B. Wolfe, E. Perrin, J. A. Simpson, J. A. Kropp Schmidt, H. M. Hinkle, L. T. Keding, R. T. Behrens, D. T. Evans, D. B. Kaufman, J. A. Thomson, T. G. Golos, M. E. Brown
Summary: Engraftment of rhesus macaque hematopoietic tissues in immune-deficient mice yields a robust BLT/NeoThy-type primatized mouse model for studying nonhuman primate hematopoiesis and immune function in vivo.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Miles C. Smith, Lalitha R. Belur, Andrea D. Karlen, Olivia Erlanson, Kelly M. Podetz-Pedersen, Jessica McKenzie, Jenn Detellis, Khatuna Gagnidze, Geoffrey Parsons, Nicholas Robinson, Shelby Labarre, Saumil Shah, Justin Furcich, Troy C. Lund, Hsing-Chen Tsai, R. Scott McIvor, Melissa Bonner
Summary: Mucopolysaccharidosis type II, or Hunter syndrome, is a genetic lysosomal disease that currently only has enzyme replacement therapy as an approved treatment option. However, this therapy does not improve neurological symptoms. A study using a mouse model found that hematopoietic stem and progenitor cells transduced with a lentiviral vector carrying a specific gene sequence could effectively treat the disease and restore enzyme levels in the brain, preventing cognitive deficits.
HUMAN GENE THERAPY
(2022)
Article
Cell Biology
Junmo Wu, Yu Kang, Xiang Luo, Shaoxing Dai, Yuxi Shi, Zhuoyao Li, Zengli Tang, Zhenzhen Chen, Ran Zhu, Pengpeng Yang, Zifan Li, Hong Wang, Xinglong Chen, Ziyi Zhao, Weizhi Ji, Yuyu Niu
Summary: This study presents a chemically defined, xeno-free culture system for culturing and deriving monkey pluripotent stem cells (PSCs) and demonstrates the ability to integrate bioluminescent reporter genes into monkey PSCs and track them in chimeric embryos in vivo and in vitro. The findings have significant implications for primate stem cell engineering and the use of chimeric monkey models in clinical studies.
Article
Biotechnology & Applied Microbiology
Sophie Ramadier, Anne Chalumeau, Tristan Felix, Nadia Othman, Sherazade Aknoun, Antonio Casini, Giulia Maule, Cecile Masson, Anne De Cian, Giacomo Frati, Megane Brusson, Jean-Paul Concordet, Marina Cavazzana, Anna Cereseto, Wassim El Nemer, Mario Amendola, Benoit Wattellier, Vasco Meneghini, Annarita Miccio
Summary: In this study, a novel therapeutic approach combining LV-based gene addition and CRISPR-Cas9 strategies was developed to treat Sickle Cell Disease. This versatile platform reduced the expression of sickle beta-globin and increased the expression of anti-sickling globins, resulting in improved treatment efficacy.
Review
Medicine, General & Internal
Akshay Sharma, Vanitha A. Jagannath, Latika Puri
Summary: Thalassaemia is an autosomal recessive blood disorder caused by mutations in globin genes, leading to reduced synthesis of certain globin chains. Current treatment involves regular transfusions and iron chelation therapy, with allogeneic hematopoietic stem cell transplantation being the only potentially curative option. Gene therapy for thalassaemia is also emerging as a promising alternative with curative potential.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)
Article
Virology
Ekati Drakopoulou, Maria Georgomanoli, Carsten W. Lederer, Fottes Panetsos, Marina Kleanthous, Ersi Voskaridou, Dimitrios Valakos, Eleni Papanikolaou, Nicholas P. Anagnou
Summary: This study demonstrates the efficacy of the optimized gamma-globin lentiviral vector in improving the phenotype of sickle cell disease in vitro, highlighting its potential for future clinical trials.
Article
Biochemistry & Molecular Biology
Farid Boulad, Aurelio Maggio, Xiuyan Wang, Paolo Moi, Santina Acuto, Friederike Kogel, Chayamon Takpradit, Susan Prockop, Jorge Mansilla-Soto, Annalisa Cabriolu, Ashlesha Odak, Jinrong Qu, Keyur Thummar, Fang Du, Lingbo Shen, Simona Raso, Rita Barone, Rosario Di Maggio, Lorella Pitrolo, Antonino Giambona, Maura Mingoia, John K. Everett, Pascha Hokama, Aoife M. Roche, Vito Adrian Cantu, Hriju Adhikari, Shantan Reddy, Eric Bouhassira, Narla Mohandas, Frederic D. Bushman, Isabelle Riviere, Michel Sadelain
Summary: This study reports the 6-8-year follow-up of four adult patients with transfusion-dependent beta-thalassemia who received autologous CD34(+) cells transduced with a lentiviral globin vector. The findings suggest that non-myeloablative conditioning can achieve durable stem cell engraftment, but a minimum CD34(+) cell transduction requirement is necessary for effective therapy. The study highlights the importance of monitoring patients with globin vectors.
Article
Cell Biology
Feiyang Li, Jianlong Sun
Summary: Trained immunity inducers can cause epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) to generate long-lasting immune protection. However, the differentiation kinetics of HSPCs after exposure to inducers of trained immunity remains unclear. In this study, researchers found that the differentiation behaviors of certain HSPCs were hardly affected by the induction of trained immunity. These results suggest that changed kinetics in cell differentiation is not the cause of enhanced myelopoiesis upon secondary immune challenges.
Article
Multidisciplinary Sciences
M. N. Gnanapragasam, A. Planutis, J. A. Glassberg, J. J. Bieker
Summary: The onset of erythropoiesis is regulated by various factors, including the zinc finger transcription factor KLF1. A conserved enhancer element in KLF1 intron 1 is important for optimal KLF1 levels during erythropoiesis. This site exhibits cell-type specificity and binds multiple transcription factors. Editing this region reduces KLF1 expression, but downstream effects vary, suggesting a buffered state that maintains overall KLF1 activity.
SCIENTIFIC REPORTS
(2023)
Article
Hematology
Valentina Vavassori, Samuele Ferrari, Stefano Beretta, Claudia Asperti, Luisa Albano, Andrea Annoni, Chiara Gaddoni, Angelica Varesi, Monica Soldi, Alessandro Cuomo, Tiziana Bonaldi, Marina Radrizzani, Ivan Merelli, Luigi Naldini
Summary: Ex vivo gene editing in T cells and HSPCs can be improved by using lipid nanoparticles for RNA delivery, which reduces cell death and improves cell growth, leading to better editing efficiency.
Article
Biotechnology & Applied Microbiology
Adrian Westhaus, Marti Cabanes-Creus, Timo Jonker, Erwan Sallard, Renina Gale Navarro, Erhua Zhu, Grober Baltazar Torres, Scott Lee, Patrick Wilmott, Anai Gonzalez-Cordero, Giorgia Santilli, Adrian J. Thrasher, Ian E. Alexander, Leszek Lisowski
Summary: This study validated a functional transduction (FT)-based method for rapid identification of novel AAV variants. Compared with existing replication-competent (RC) strategies, the mRNA-based FT selection was found to be the most optimal AAV selection method. The study also revealed that the AAV-p40 promoter is a ubiquitously active promoter that can be modified for cell-type-specific expression by incorporating specific binding sites.
HUMAN GENE THERAPY
(2022)
Article
Medicine, Research & Experimental
Marti Cabanes-Creus, Renina Gale Navarro, Erhua Zhu, Grober Baltazar, Sophia H. Y. Liao, Matthieu Drouyer, Anais K. Amaya, Suzanne Scott, Loan Hanh Nguyen, Adrian Westhaus, Matthias Hebben, Laurence O. W. Wilson, Adrian J. Thrasher, Ian E. Alexander, Leszek Lisowski
Summary: Recent clinical successes have increased interest in using adeno-associated virus (AAV) vectors for therapeutic gene delivery. This study bioengineered a new generation of AAV vectors, called AAV-SYDs, with increased human hepatotropism. By employing directed evolution and domain-swapping strategies, the key capsid residues responsible for enhanced primary human hepatocyte uptake and transgene expression were identified and studied. These findings highlight the potential of AAV-SYDs as liver gene therapy vectors and provide insights into their enhanced transduction profile.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Cell Biology
Ronnie Blazev, Christian S. Carl, Yaan-Kit Ng, Jeffrey Molendijk, Christian T. Voldstedlund, Yuanyuan Zhao, Di Xiao, Andrew J. Kueh, Paula M. Miotto, Vanessa R. Haynes, Justin P. Hardee, Jin D. Chung, James W. McNamara, Hongwei Qian, Paul Gregorevic, Jonathan S. Oakhill, Marco J. Herold, Thomas E. Jensen, Leszek Lisowski, Gordon S. Lynch, Garron T. Dodd, Matthew J. Watt, Pengyi Yang, Bente Kiens, Erik A. Richter, Benjamin L. Parker
Summary: This study identified divergent and common signaling networks during and after different exercise modalities through phosphoproteomic analysis. It also revealed C18ORF25 as a regulator of exercise signaling and muscle function.
Article
Gastroenterology & Hepatology
Nadja Meumann, Marti Cabanes-Creus, Moritz Ertelt, Renina Gale Navarro, Julie Lucifora, Qinggong Yuan, Karin Nien-Huber, Ahmed Abdelrahman, Xuan-Khang Vu, Liang Zhang, Ann-Christin Franke, Christian Schmithals, Albrecht Piiper, Annabelle Vogt, Maria Gonzalez-Carmona, Jochen T. Frueh, Evelyn Ullrich, Philip Meuleman, Steven R. Talbot, Margarete Odenthal, Michael Ott, Erhard Seifried, Clara T. Schoeder, Joachim Schwable, Leszek Lisowski, Hildegard Buning
Summary: This article reports two gene vector variants, MLIV.K and MLIV.A, which were obtained through in vivo AAV peptide display selection in mice. They showed improved hepatocyte targeting and transduction efficiency compared to AAV2 and AAV8, and have potential for liver disease treatment.
Review
Biotechnology & Applied Microbiology
Ramon Roca-Pinilla, Leszek Lisowski, Anna Aris, Elena Garcia-Fruitos
Summary: Host defense peptides (HDPs) are small proteins with potent antibacterial and immunomodulatory activities, suitable for clinical applications. Traditional methods of producing antimicrobial peptides are expensive and toxic, making recombinant production of HDPs an alternative. This review explores different strategies for optimizing HDPs, including fine-tuning their activities, bioengineering, and recombinant production in various cell factories.
MICROBIAL CELL FACTORIES
(2022)
Article
Multidisciplinary Sciences
Lay Khoon Too, Weiyong Shen, Dario A. Protti, Atomu Sawatari, Dylan A. Black, Catherine A. Leamey, Jin Y. Huang, So-Ra Lee, Ashish E. Mathai, Leszek Lisowski, John Y. Lin, Mark C. Gillies, Matthew P. Simunovic
Summary: The newly described high sensitivity opsin, bReaChES, has the potential to restore vision in a murine model of severe early-onset retinal degeneration and may have therapeutic effects in human retinal degeneration.
SCIENTIFIC REPORTS
(2022)
Article
Biology
Jeffrey Molendijk, Ronnie Blazev, Richard J. Mills, Yaan-Kit Ng, Kevin Watt, Daryn Chau, Paul Gregorevic, Peter J. Crouch, James B. W. Hilton, Leszek Lisowski, Peixiang Zhang, Karen Reue, Aldons J. Lusis, James E. Hudson, David E. James, Marcus M. Seldin, Benjamin L. Parker
Summary: By conducting proteomic analysis and correlation network analysis, multiple regulators of muscle function were identified, providing new insights for improving muscle function.
Review
Chemistry, Medicinal
Jessica Merjane, Roger Chung, Rickie Patani, Leszek Lisowski
Summary: Despite the mysterious etiology, differentiated treatments are required for ALS to address both familial and sporadic cases. Targeting mechanisms of defective protein homeostasis and RNA processing, as well as exploring the use of gene therapy through adeno-associated virus (AAV) for gene delivery to the CNS, might provide potential therapeutic interventions. Overall, there is a strong need for disease modifying treatments for ALS that can effectively treat the full spectrum of cases.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Gastroenterology & Hepatology
Ngee-Soon Lau, Mark Ly, Claude Dennis, Kasper Ewenson, Hayden Ly, Joanna L. Huang, Marti Cabanes-Creus, Sumon Chanda, Chuanmin Wang, Leszek Lisowski, Ken Liu, James Kench, Geoffrey McCaughan, Michael Crawford, Carlo Pulitano
Summary: Liver splitting during normothermic machine perfusion has the potential to revolutionize split liver transplantation. We developed a technique to reliably achieve two grafts from a single donor liver, allowing for semi-elective transplantation and sophisticated graft assessment prior to implant. This method successfully split 10 whole livers into 20 partial grafts, with a high rate of graft survival.
Meeting Abstract
Cell & Tissue Engineering
Shiva Soltani Dehnavi, Arianna Cembran, Leszek Lisowski, Alan Harvey, Clare Parish, Richard Williams, David Nisbet
TISSUE ENGINEERING PART A
(2022)
Meeting Abstract
Immunology
Ngee-Soon Lau, Mark Ly, Claude Dennis, Joanna Lou Huang, Joanna Huang, Andrew Jacques, Marti Cabanes-Creus, Shamus Toomath, Nicole Mestrovic, Paul Yousif, Sumon Chanda, Chuanmin Wang, Leszek Lisowski, Ken Liu, James Kench, Geoffrey McCaughan, Michael Crawford, Carlo Pulitano
Meeting Abstract
Biochemistry & Molecular Biology
Dzung Do-Ha, Sonia Sanz Munoz, Claire H. Stevens, Mauricio Castro Cabral-da-Silva, Rachelle Balez, Predrag Kalajdzic, Leszek Lisowski, Martin Engel, Yossi Buskila, Lezanne Ooi
JOURNAL OF NEUROCHEMISTRY
(2022)
Meeting Abstract
Biotechnology & Applied Microbiology
Erwan Sallard, Eric Ehrke-Schulz, Adrian Westhaus, Marti Cabanes-Creus, Leszek Lisowski, Anja Ehrhardt
Meeting Abstract
Biotechnology & Applied Microbiology
Adrian Westhaus, Kenneth Hsu, Maddison Knight, Thomas E. Whittaker, Benjamin C. Houghton, Santiago Mesa Mora, Predrag Kalajdzic, Adrian J. Thrasher, Giorgia Santilli, Leszek Lisowski
Meeting Abstract
Biotechnology & Applied Microbiology
Marti Cabanes-Creus, Renina G. Navarro, Sophia H. Y. Liao, Ngee-Soon Lau, Mark Ly, Grober Baltazar, Maddison Knight, Erhua Zhu, Geoffrey McCaughan, Michael Crawford, Ian E. Alexander, Carlo Pulitano, Leszek Lisowski