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1. An in vivo duck hepatitis B virus model recapitulates key aspects of nucleic acid polymer treatment outcomes in chronic hepatitis B patients

Author

Debing, Yannick, Vanrusselt, Hannah, Degrauwe, Lars, Silva de Oliveira, Daniel Apolônio, Kariuki, Christopher Kinyanjui, Ebwanga, Ebanja Joseph, Bashir, Shahbaz, Merckx, Wouter, Thatikonda, Santhosh Kumar, Rajwanshi, Vivek, Gohil, Vikrant, Hong, Jin, Kum, Dieudonné Buh, Acosta Sanchez, Abel, Chanda, Sushmita, Blatt, Lawrence M., Jekle, Andreas, Symons, Julian A., Smith, David B., Raboisson, Pierre, Lin, Tse-I, Beigelman, Leonid, and Paeshuyse, Jan

Published
2024
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2. Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis

Author

Sadiku, Pranvera, Willson, Joseph A., Ryan, Eilise M., Sammut, David, Coelho, Patricia, Watts, Emily R., Grecian, Robert, Young, Jason M., Bewley, Martin, Arienti, Simone, Mirchandani, Ananda S., Sanchez Garcia, Manuel A., Morrison, Tyler, Zhang, Ailing, Reyes, Leila, Griessler, Tobias, Jheeta, Privjyot, Paterson, Gordon G., Graham, Christopher J., Thomson, John P., Baillie, Kenneth, Thompson, A.A. Roger, Morgan, Jessie-May, Acosta-Sanchez, Abel, Dardé, Veronica M., Duran, Jordi, Guinovart, Joan J., Rodriguez-Blanco, Gio, Von Kriegsheim, Alex, Meehan, Richard R., Mazzone, Massimiliano, Dockrell, David H., Ghesquiere, Bart, Carmeliet, Peter, Whyte, Moira K.B., and Walmsley, Sarah R.

Published
2021
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3. Novel non-HAP class A HBV capsid assembly modulators have distinct in vitro and in vivo profiles

Author

Vanrusselt, Hannah, primary, Kum, Dieudonné Buh, additional, Taverniti, Valerio, additional, Liu, Cheng, additional, Acosta Sanchez, Abel, additional, Corthout, Nikky, additional, Munck, Sebastian, additional, Baumert, Thomas F., additional, Beigelman, Leonid, additional, Blatt, Lawrence M., additional, Symons, Julian A., additional, Deval, Jerome, additional, Raboisson, Pierre, additional, Verrier, Eloi R., additional, Jekle, Andreas, additional, Vendeville, Sandrine, additional, and Debing, Yannick, additional

Published
2023
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4. Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk

Author

Mátrai, Janka, Cantore, Alessio, Bartholomae, Cynthia C., Annoni, Andrea, Wang, Wei, Acosta-Sanchez, Abel, Samara-Kuko, Ermira, De Waele, Liesbeth, Ma, Ling, Genovese, Pietro, Damo, Martina, Arens, Anne, Goudy, Kevin, Nichols, Timothy C., von Kalle, Christof, L. Chuah, Marinee K., Roncarolo, Maria Grazia, Schmidt, Manfred, VandenDriessche, Thierry, and Naldini, Luigi

Published
2011
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5. Genome-wide Computational Analysis Reveals Cardiomyocyte-specific Transcriptional Cis-regulatory Motifs That Enable Efficient Cardiac Gene Therapy

Author

Rincon, Melvin Y, primary, Sarcar, Shilpita, additional, Danso-Abeam, Dina, additional, Keyaerts, Marleen, additional, Matrai, Janka, additional, Samara-Kuko, Ermira, additional, Acosta-Sanchez, Abel, additional, Athanasopoulos, Takis, additional, Dickson, George, additional, Lahoutte, Tony, additional, De Bleser, Pieter, additional, VandenDriessche, Thierry, additional, and Chuah, Marinee K, additional

Published
2015
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6. Sustained therapeutic factor IX expression in liver using integration-deficient lentiviral vectors

Author

Màtrai, J., Chuah, Marinee, Cantore, Alessio, Acosta-Sanchez, Abel, Bartholomae, Cynthia, Samara-Kuko, E., Ma, Ling, De Waele, Liesbeth, Schmidt, Manfred, Von Kalle, C., Naldini, Luigi, VandenDriessche, Thierry, Division of Gene Therapy & Regenerative Medicine, and Cell Biology and Histology

Subjects
therapeutic factor IX expression, integration-deficient lentiviral vectors, liver
Published
2009

7. Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates

Author

Mátés, L., Chuah, Marinee, Belay, E., Jerchow, B., Manoj, N., Acosta-Sanchez, Abel, Grzela, D., Schmitt, A., Becker, K., Màtrai, J., Ma, L., Samara-Kuko, E., Gysemans, C., Pryputniewicz, D., Miskey, C., Fletcher, B., VandenDriessche, Thierry, Ivics, Z., Izsvák, Z., Division of Gene Therapy & Regenerative Medicine, and Cell Biology and Histology

Subjects
Mice, Transgenic/genetics, mice, Sequence Homology, Amino Acid, Molecular Sequence Data, phylogeny, DNA Transposable Elements/genetics, Evolution, Molecular, Transposases/chemistry, Vertebrates/genetic, Animals, Humans, Amino Acid Sequence, Transposases/genetics, Sequence Alignment, Conserved Sequence
Abstract

The Sleeping Beauty (SB) transposon is a promising technology platform for gene transfer in vertebrates; however, its efficiency of gene insertion can be a bottleneck in primary cell types. A large-scale genetic screen in mammalian cells yielded a hyperactive transposase (SB100X) with approximately 100-fold enhancement in efficiency when compared to the first-generation transposase. SB100X supported 35-50% stable gene transfer in human CD34(+) cells enriched in hematopoietic stem or progenitor cells. Transplantation of gene-marked CD34(+) cells in immunodeficient mice resulted in long-term engraftment and hematopoietic reconstitution. In addition, SB100X supported sustained (>1 year) expression of physiological levels of factor IX upon transposition in the mouse liver in vivo. Finally, SB100X reproducibly resulted in 45% stable transgenesis frequencies by pronuclear microinjection into mouse zygotes. The newly developed transposase yields unprecedented stable gene transfer efficiencies following nonviral genedelivery that compare favorably to stable transduction efficiencies with integrating viral vectors and is expected to facilitate widespread applications in functional genomics and gene therapy.

Published
2009

8. IL-10 dampens TNF/inducible nitric oxide synthase-producing dendritic cell-mediated pathogenicity during parasitic infection

Author

Guilliams, M., Movahedi, K., Bosschaerts, Tom, VandenDriessche, Thierry, Chuah, Marinee, Michel, Herin, Acosta-Sanchez, Abel, Ma, L., Moser, M., Van Ginderachter, J.a., Division of Gene Therapy & Regenerative Medicine, and Cell Biology and Histology

Subjects
mice, Nitric Oxide/antagonists & inhibitors, Trypanosomiasis, African/enzymology, Nitric Oxide Synthase Type II/biosynthesis, Genetic Vectors/immunology, Parasitemia/enzymology, Tumor Necrosis Factor-alpha/biosynthesis, Cell Differentiation/immunology, Immunophenotyping, Cell Line, Tumor Necrosis Factor-alpha/antagonists & inhibito, Monocytes/metabolism, parasitic diseases, Trypanosomiasis, African/immunology, Interleukin-10/deficiency, Interleukin-10/genetics, Mice, Knockout, Immunity, Cellular, Mice, Inbred BALB C, Interleukin-10/physiology, Nitric Oxide Synthase Type II/antagonists & inhibi, Monocytes/pathology, Monocytes/enzymology, Nitric Oxide/biosynthesis, Parasitemia/pathology, Monocytes/immunology, Dendritic Cells/enzymology, Trypanosoma brucei brucei/pathogenicity, Mice, Inbred C57BL, Parasitemia/immunology, Trypanosoma brucei brucei/immunology, Interleukin-10/administration & dosage, Trypanosomiasis, African/pathology, Trypanosomiasis, African/prevention & contro, Genetic Vectors/administration & dosage, Parasitemia/prevention & control
Abstract

Antiparasite responses are associated with the recruitment of monocytes that differentiate to macrophages and dendritic cells at the site of infection. Although classically activated monocytic cells are assumed to be the major source of TNF and NO during Trypanosoma brucei brucei infection, their cellular origin remains unclear. In this study, we show that bone marrow-derived monocytes accumulate and differentiate to TNF/inducible NO synthase-producing dendritic cells (TIP-DCs) in the spleen, liver, and lymph nodes of T. brucei brucei-infected mice. Although TIP-DCs have been shown to play a beneficial role in the elimination of several intracellular pathogens, we report that TIP-DCs, as a major source of TNF and NO in inflamed organs, could contribute actively to tissue damage during the chronic stage of T. brucei brucei infection. In addition, the absence of IL-10 leads to enhanced differentiation of monocytes to TIP-DCs, resulting in exacerbated pathogenicity and early death of the host. Finally, we demonstrate that sustained production of IL-10 following IL-10 gene delivery treatment with an adeno-associated viral vector to chronically infected mice limits the differentiation of monocytes to TIP-DCs and protects the host from tissue damage.

Published
2009

9. Hyperactive transposons for gene delivery into iPS and adult stem cells: a novel paradigm for coaxed differentiation

Author

Belay, E., Màtrai, J., Quatrocelli, Mattia, Mátés, L., Acosta-Sanchez, Abel, Bru, Pau, Geraerts, M., Vanuytsel, Kim, Yan, B., Ma, Ling, Bueren, Juan, Vermeesch, Joris, Samara-Kuko, E., Verfaillie, Catherine, Sampaolesi, Maurillio, Ivics, Z., Izsvák, Z., VandenDriessche, Thierry, Chuah, Marinee, Division of Gene Therapy & Regenerative Medicine, and Cell Biology and Histology

Subjects
Genes, iPS, adult stem cells
Published
2009

10. De Novo Identification of Combinations of Hepatocyte-Specific Transcription Factor Binding Sites Using a Novel Bioinformatics Algorithm Yield Robust Liver-Specific Expression

Author

Petrus, Inge, Chuah, Marinee, Acosta-Sanchez, Abel, Bing, Yan, De Bleser, Pieter, Hooghe, Bart, Màtrai, J., Ma, L., Samara-Kuko, E., Van Roy, Frans, VandenDriessche, Thierry, Cell Biology and Histology, and Division of Gene Therapy & Regenerative Medicine

Subjects
Hepatocyte-Specific, Bioinformatics Algorithm, liver
Abstract

no abstract available

Published
2009

11. Novel Transposases Obtained by Darwinian Evolution and Selection Result in Stable Gene Transfer in Cd34+Cells and Efficient Gene Marking In Vivo Following Hematopoietic Reconstitution

Author

Belay, E., VandenDriessche, Thierry, Mátés, L., Janka, M., Ma, L., Acosta-Sanchez, Abel, Samara-Kuko, E., Miskey, C., Ivics, Z., Izsvák, Z., Chuah, Marinee, Division of Gene Therapy & Regenerative Medicine, and Cell Biology and Histology

Subjects
Gene Markers, IVF, Darwinian Evolution, gene transfer, Cd34+Cells, Hematopoietic Reconstitution
Published
2009

12. Liver-Specific Transcriptional Modules Identified by Genome-Wide In Silico Analysis Enable Efficient Gene Therapy in Mice and Non-Human Primates

Author

Chuah, Marinee K, primary, Petrus, Inge, additional, De Bleser, Pieter, additional, Le Guiner, Caroline, additional, Gernoux, Gwladys, additional, Adjali, Oumeya, additional, Nair, Nisha, additional, Willems, Jessica, additional, Evens, Hanneke, additional, Rincon, Melvin Y, additional, Matrai, Janka, additional, Di Matteo, Mario, additional, Samara-Kuko, Ermira, additional, Yan, Bing, additional, Acosta-Sanchez, Abel, additional, Meliani, Amine, additional, Cherel, Ghislaine, additional, Blouin, Véronique, additional, Christophe, Olivier, additional, Moullier, Philippe, additional, Mingozzi, Federico, additional, and VandenDriessche, Thierry, additional

Published
2014
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13. Novel hyperactive transposons for genetic modification of induced pluripotent and adult stem cells: A nonviral paradigm for coaxed differentiation

Author

Belay, Eyayu, Mátrai, Janka, Acosta-Sanchez, Abel, Ma, Ling, Yan, Bing, Rincón, Melvin Yesid, Samara-Kuko, Ermira, VandenDriessche, Thierry, Chuah Lay Khim, Marinee, Mátés, Lajos, Ivics, Zoltán, Izsvák, Zsuzsanna, Quattrocelli, Mattia, Sancho-Bru, Pau, Geraerts, Martine, Verfaillie, Catherine, Sampaolesi, Maurilio, Vermeesch, Joris Robert, Belay, Eyayu, Mátrai, Janka, Acosta-Sanchez, Abel, Ma, Ling, Yan, Bing, Rincón, Melvin Yesid, Samara-Kuko, Ermira, VandenDriessche, Thierry, Chuah Lay Khim, Marinee, Mátés, Lajos, Ivics, Zoltán, Izsvák, Zsuzsanna, Quattrocelli, Mattia, Sancho-Bru, Pau, Geraerts, Martine, Verfaillie, Catherine, Sampaolesi, Maurilio, and Vermeesch, Joris Robert

Abstract

Adult stem cells and induced pluripotent stem cells (iPS) hold great promise for regenerative medicine. The development of robust nonviral approaches for stem cell gene transfer would facilitate functional studies and potential clinical applications. We have previously generated hyperactive transposases derived from Sleeping Beauty, using an in vitro molecular evolution and selection paradigm. We now demonstrate that these hyperactive transposases resulted in superior gene transfer efficiencies and expression in mesenchymal and muscle stem/progenitor cells, consistent with higher expression levels of therapeutically relevant proteins including coagulation factor IX. Their differentiation potential and karyotype was not affected. Moreover, stable transposition could also be achieved in iPS, which retained their ability to differentiate along neuronal, cardiac, and hepatic lineages without causing cytogenetic abnormalities. Most importantly, transposonmediated delivery of the myogenic PAX3 transcription factor into iPS coaxed their differentiation into MYOD+ myogenic progenitors and multinucleated myofibers, suggesting that PAX3 may serve as a myogenic "molecular switch" in iPS. Hence, this hyperactive transposon system represents an attractive nonviral gene transfer platform with broad implications for regenerative medicine, cell and gene therapy. © AlphaMed Press., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

Published
2010

14. IL-10 dampens TNF/inducible nitric oxide synthase-producing dendritic cell-mediated pathogenicity during parasitic infection.

Author

Guilliams, Martin, Movahedi, Kiavash, Bosschaerts, Tom, VandenDriessche, Thierry, Chuah Lay Khim, Marinee, Hérin, Michel, Acosta-Sanchez, Abel, Ma, Ling, Moser, Muriel, Van Ginderachter, Jo A, Brys, Lea, De Baetselier, Patrick, Beschin, A, Guilliams, Martin, Movahedi, Kiavash, Bosschaerts, Tom, VandenDriessche, Thierry, Chuah Lay Khim, Marinee, Hérin, Michel, Acosta-Sanchez, Abel, Ma, Ling, Moser, Muriel, Van Ginderachter, Jo A, Brys, Lea, De Baetselier, Patrick, and Beschin, A

Abstract

Antiparasite responses are associated with the recruitment of monocytes that differentiate to macrophages and dendritic cells at the site of infection. Although classically activated monocytic cells are assumed to be the major source of TNF and NO during Trypanosoma brucei brucei infection, their cellular origin remains unclear. In this study, we show that bone marrow-derived monocytes accumulate and differentiate to TNF/inducible NO synthase-producing dendritic cells (TIP-DCs) in the spleen, liver, and lymph nodes of T. brucei brucei-infected mice. Although TIP-DCs have been shown to play a beneficial role in the elimination of several intracellular pathogens, we report that TIP-DCs, as a major source of TNF and NO in inflamed organs, could contribute actively to tissue damage during the chronic stage of T. brucei brucei infection. In addition, the absence of IL-10 leads to enhanced differentiation of monocytes to TIP-DCs, resulting in exacerbated pathogenicity and early death of the host. Finally, we demonstrate that sustained production of IL-10 following IL-10 gene delivery treatment with an adeno-associated viral vector to chronically infected mice limits the differentiation of monocytes to TIP-DCs and protects the host from tissue damage., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Published
2009

15. Novel Hyperactive Transposons for Genetic Modification of Induced Pluripotent and Adult Stem Cells: A Nonviral Paradigm for Coaxed Differentiation

Author

Belay, Eyayu, primary, Mátrai, Janka, additional, Acosta-Sanchez, Abel, additional, Ma, Ling, additional, Quattrocelli, Mattia, additional, Mátés, Lajos, additional, Sancho-Bru, Pau, additional, Geraerts, Martine, additional, Yan, Bing, additional, Vermeesch, Joris, additional, Rincón, Melvin Yesid, additional, Samara-Kuko, Ermira, additional, Ivics, Zoltán, additional, Verfaillie, Catherine, additional, Sampaolesi, Maurilio, additional, Izsvák, Zsuzsanna, additional, VandenDriessche, Thierry, additional, and Chuah, Marinee K. L., additional

Published
2010
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16. Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates

Author

Mátés, Lajos, primary, Chuah, Marinee K L, additional, Belay, Eyayu, additional, Jerchow, Boris, additional, Manoj, Namitha, additional, Acosta-Sanchez, Abel, additional, Grzela, Dawid P, additional, Schmitt, Andrea, additional, Becker, Katja, additional, Matrai, Janka, additional, Ma, Ling, additional, Samara-Kuko, Ermira, additional, Gysemans, Conny, additional, Pryputniewicz, Diana, additional, Miskey, Csaba, additional, Fletcher, Bradley, additional, VandenDriessche, Thierry, additional, Ivics, Zoltán, additional, and Izsvák, Zsuzsanna, additional

Published
2009
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17. IL-10 Dampens TNF/Inducible Nitric Oxide Synthase-Producing Dendritic Cell-Mediated Pathogenicity during Parasitic Infection

Author

Guilliams, Martin, primary, Movahedi, Kiavash, additional, Bosschaerts, Tom, additional, VandenDriessche, Thierry, additional, Chuah, Marinee Khim, additional, Hérin, Michel, additional, Acosta-Sanchez, Abel, additional, Ma, Ling, additional, Moser, Muriel, additional, Van Ginderachter, Jo A., additional, Brys, Lea, additional, De Baetselier, Patrick, additional, and Beschin, Alain, additional

Published
2009
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18. 24. Widespread and Efficient Gene Delivery to the Heart and Liver Using AAV Serotype 9: Implications for Cardiovascular Disease and Hemophilia

Author

VandenDriessche, Thierry, primary, Thorrez, Lieven, additional, Acosta-Sanchez, Abel, additional, Wang, Lilly, additional, Gillijns, Veerle, additional, Ling, Ma, additional, Vandenburgh, Herman, additional, Mertens, Nico, additional, Callewaert, Nico, additional, Wilson, James, additional, Collen, Desire, additional, and Chuah, Marinee, additional

Published
2006
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19. Class A capsid assembly modulator RG7907 clears HBV-infected hepatocytes through core-dependent hepatocyte death and proliferation.

Author

Kum DB, Vanrusselt H, Acosta Sanchez A, Taverniti V, Verrier ER, Baumert TF, Liu C, Deval J, Corthout N, Munck S, Beigelman L, Blatt LM, Symons JA, Raboisson P, Jekle A, Vendeville S, and Debing Y

Subjects
Mice, Animals, Hepatitis B virus, Hepatitis B Surface Antigens metabolism, Capsid metabolism, Hepatocytes metabolism, Interferon-alpha pharmacology, DNA, Viral genetics, Hepatitis B, Chronic, Hepatitis B metabolism
Abstract

Background and Aims: Effective therapies leading to a functional cure for chronic hepatitis B are still lacking. Class A capsid assembly modulators (CAM-As) are an attractive modality to address this unmet medical need. CAM-As induce aggregation of the HBV core protein (HBc) and lead to sustained HBsAg reductions in a chronic hepatitis B mouse model. Here, we investigate the underlying mechanism of action for CAM-A compound RG7907., Approach and Results: RG7907 induced extensive HBc aggregation in vitro , in hepatoma cells, and in primary hepatocytes. In the adeno-associated virus (AAV)-HBV mouse model, the RG7907 treatment led to a pronounced reduction in serum HBsAg and HBeAg, concomitant with clearance of HBsAg, HBc, and AAV-HBV episome from the liver. Transient increases in alanine transaminase, hepatocyte apoptosis, and proliferation markers were observed. These processes were confirmed by RNA sequencing, which also uncovered a role for interferon alpha and gamma signaling, including the interferon-stimulated gene 15 (ISG15) pathway. Finally, the in vitro observation of CAM-A-induced HBc-dependent cell death through apoptosis established the link of HBc aggregation to in vivo loss of infected hepatocytes., Conclusions: Our study unravels a previously unknown mechanism of action for CAM-As such as RG7907 in which HBc aggregation induces cell death, resulting in hepatocyte proliferation and loss of covalently closed circular DNA or its equivalent, possibly assisted by an induced innate immune response. This represents a promising approach to attain a functional cure for chronic hepatitis B., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Published
2023
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