140 results on '"Kajaste-Rudnitski A"'
Search Results
2. Removal of innate immune barriers allows efficient transduction of quiescent human hematopoietic stem cells
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Valeri, Erika, Unali, Giulia, Piras, Francesco, Abou-Alezz, Monah, Pais, Giulia, Benedicenti, Fabrizio, Lidonnici, Maria Rosa, Cuccovillo, Ivan, Castiglioni, Ilaria, Arévalo, Sergio, Spinozzi, Giulio, Merelli, Ivan, Behrendt, Rayk, Oo, Adrian, Kim, Baek, Landau, Nathaniel R., Ferrari, Giuliana, Montini, Eugenio, and Kajaste-Rudnitski, Anna
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- 2024
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3. In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases
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Kerzel, Thomas, Giacca, Giovanna, Beretta, Stefano, Bresesti, Chiara, Notaro, Marco, Scotti, Giulia Maria, Balestrieri, Chiara, Canu, Tamara, Redegalli, Miriam, Pedica, Federica, Genua, Marco, Ostuni, Renato, Kajaste-Rudnitski, Anna, Oshima, Masanobu, Tonon, Giovanni, Merelli, Ivan, Aldrighetti, Luca, Dellabona, Paolo, Coltella, Nadia, Doglioni, Claudio, Rancoita, Paola M.V., Sanvito, Francesca, Naldini, Luigi, and Squadrito, Mario Leonardo
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- 2023
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4. Genetic engineering meets hematopoietic stem cell biology for next-generation gene therapy
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Ferrari, Samuele, Valeri, Erika, Conti, Anastasia, Scala, Serena, Aprile, Annamaria, Di Micco, Raffaella, Kajaste-Rudnitski, Anna, Montini, Eugenio, Ferrari, Giuliana, Aiuti, Alessandro, and Naldini, Luigi
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- 2023
- Full Text
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5. Protocol to differentiate monolayer human induced pluripotent stem cells into inflammatory responsive astrocytes
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Anna Maria Sole Giordano, Monah Abou Alezz, Ivan Merelli, and Anna Kajaste-Rudnitski
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Cell Biology ,Cell Differentiation ,Immunology ,Molecular Biology ,Neuroscience ,Stem Cells ,Science (General) ,Q1-390 - Abstract
Summary: Glia, and in particular astrocytes, are one of the major players in neurological and neuroinflammatory disorders. Here, we present a protocol to efficiently generate inflammatory responsive astrocytes from human induced pluripotent stem cells in a monolayer culture. We describe steps for neural differentiation to reach a homogeneous population of neural progenitor cells, followed by their differentiation into neural/glial progenitors. Finally, we detail enrichment to a 90% pure inflammatory responsive astrocyte population.For complete details on the use and execution of this protocol, please refer to Giordano et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
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- 2023
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6. Antiviral immunity and nucleic acid sensing in haematopoietic stem cell gene engineering
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Piras, Francesco and Kajaste-Rudnitski, Anna
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- 2021
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7. Laboratory-Scale Lentiviral Vector Production and Purification for Enhanced Ex Vivo and In Vivo Genetic Engineering
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Monica Soldi, Lucia Sergi Sergi, Giulia Unali, Thomas Kerzel, Ivan Cuccovillo, Paola Capasso, Andrea Annoni, Mauro Biffi, Paola Maria Vittoria Rancoita, Alessio Cantore, Angelo Lombardo, Luigi Naldini, Mario Leonardo Squadrito, and Anna Kajaste-Rudnitski
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Lentiviral vectors ,purification process ,manufacturing ,gene therapy ,ex vivo ,in vivo ,Genetics ,QH426-470 ,Cytology ,QH573-671 - Abstract
Lentiviral vectors (LVs) are increasingly employed in gene and cell therapy. Standard laboratory production of LVs is not easily scalable, and research-grade LVs often contain contaminants that can interfere with downstream applications. Moreover, purified LV production pipelines have been developed mainly for costly, large-scale, clinical-grade settings. Therefore, a standardized and cost-effective process is still needed to obtain efficient, reproducible, and properly executed experimental studies and preclinical development of ex vivo and in vivo gene therapies, as high infectivity and limited adverse reactions are important factors potentially influencing experimental outcomes also in preclinical settings. We describe here an optimized laboratory-scale workflow whereby an LV-containing supernatant is purified and concentrated by sequential chromatographic steps, obtaining biologically active LVs with an infectious titer and specific activity in the order of 109 transducing unit (TU)/mL and 5 × 104 TU/ng of HIV Gag p24, respectively. The purification workflow removes >99% of the starting plasmid, DNA, and protein impurities, resulting in higher gene transfer and editing efficiency in severe combined immunodeficiency (SCID)-repopulating hematopoietic stem and progenitor cells (HSPCs) ex vivo, as well as reduced activation of inflammatory responses ex vivo and in vivo as compared to TU-matched, laboratory-grade vectors. Our results highlight the value of accessible purified LV production for experimental studies and preclinical testing.
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- 2020
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- View/download PDF
8. D-mannose suppresses macrophage IL-1β production
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Simone Torretta, Alessandra Scagliola, Luisa Ricci, Francesco Mainini, Sabrina Di Marco, Ivan Cuccovillo, Anna Kajaste-Rudnitski, David Sumpton, Kevin M. Ryan, and Simone Cardaci
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Science - Abstract
Mannose is present at trace levels in blood and regulates cancer growth. Here the authors show that supraphysiological levels of mannose can also regulate macrophages, limiting their production of IL-1β and increasing resistance of mice to LPS-induced endotoxemia and DSS-induced colitis.
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- 2020
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9. Efficient gene editing of human long-term hematopoietic stem cells validated by clonal tracking
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Ferrari, Samuele, Jacob, Aurelien, Beretta, Stefano, Unali, Giulia, Albano, Luisa, Vavassori, Valentina, Cittaro, Davide, Lazarevic, Dejan, Brombin, Chiara, Cugnata, Federica, Kajaste-Rudnitski, Anna, Merelli, Ivan, Genovese, Pietro, and Naldini, Luigi
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- 2020
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10. Corrigendum: Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer
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Michela Comi, Giada Amodio, Laura Passeri, Marta Fortunato, Francesca Romana Santoni de Sio, Grazia Andolfi, Anna Kajaste-Rudnitski, Fabio Russo, Luca Cesana, and Silvia Gregori
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dendritic cells ,IL-10 ,cell therapy ,immune tolerance ,allogeneic transplantation ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2021
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11. D-mannose suppresses macrophage IL-1β production
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Torretta, Simone, Scagliola, Alessandra, Ricci, Luisa, Mainini, Francesco, Di Marco, Sabrina, Cuccovillo, Ivan, Kajaste-Rudnitski, Anna, Sumpton, David, Ryan, Kevin M., and Cardaci, Simone
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- 2020
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12. Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer
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Michela Comi, Giada Amodio, Laura Passeri, Marta Fortunato, Francesca Romana Santoni de Sio, Grazia Andolfi, Anna Kajaste-Rudnitski, Fabio Russo, Luca Cesana, and Silvia Gregori
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dendritic cells ,IL-10 ,cell therapy ,immune tolerance ,allogeneic transplantation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The prominent role of dendritic cells (DC) in promoting tolerance and the development of methods to generate clinical grade products allowed the clinical application of tolerogenic DC (tolDC)-based therapies for controlling unwanted immune responses. We established an efficient method to generate tolerogenic human DC, producing supra-physiological levels of IL-10, by genetically engineering monocyte-derived DC with a bidirectional Lentiviral Vector (bdLV) encoding for IL-10 and a marker gene. DCIL−10 are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DCIL−10 in a humanized mouse model dampens allogeneic T cell recall responses, while murine DCIL−10 delays acute graft-vs.-host disease in mice. Our report outlines an efficient method to transduce human myeloid cells with large-size LV and shows that stable over-expression of IL-10 generates an effective cell product for future clinical applications in the contest of allogeneic transplantation.
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- 2020
- Full Text
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13. Lentiviral vectors escape innate sensing but trigger p53 in human hematopoietic stem and progenitor cells
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Francesco Piras, Michela Riba, Carolina Petrillo, Dejan Lazarevic, Ivan Cuccovillo, Sara Bartolaccini, Elia Stupka, Bernhard Gentner, Davide Cittaro, Luigi Naldini, and Anna Kajaste‐Rudnitski
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gene therapy ,hematopoietic stem and progenitor cells ,innate sensing ,lentiviral vectors ,p53 signaling ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Abstract Clinical application of lentiviral vector (LV)‐based hematopoietic stem and progenitor cells (HSPC) gene therapy is rapidly becoming a reality. Nevertheless, LV‐mediated signaling and its potential functional consequences on HSPC biology remain poorly understood. We unravel here a remarkably limited impact of LV on the HSPC transcriptional landscape. LV escaped innate immune sensing that instead led to robust IFN responses upon transduction with a gamma‐retroviral vector. However, reverse‐transcribed LV DNA did trigger p53 signaling, activated also by non‐integrating Adeno‐associated vector, ultimately leading to lower cell recovery ex vivo and engraftment in vivo. These effects were more pronounced in the short‐term repopulating cells while long‐term HSC frequencies remained unaffected. Blocking LV‐induced signaling partially rescued both apoptosis and engraftment, highlighting a novel strategy to further dampen the impact of ex vivo gene transfer on HSPC. Overall, our results shed light on viral vector sensing in HSPC and provide critical insight for the development of more stealth gene therapy strategies.
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- 2017
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14. Efficient Ex Vivo Engineering and Expansion of Highly Purified Human Hematopoietic Stem and Progenitor Cell Populations for Gene Therapy
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Erika Zonari, Giacomo Desantis, Carolina Petrillo, Francesco E. Boccalatte, Maria Rosa Lidonnici, Anna Kajaste-Rudnitski, Alessandro Aiuti, Giuliana Ferrari, Luigi Naldini, and Bernhard Gentner
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Summary: Ex vivo gene therapy based on CD34+ hematopoietic stem cells (HSCs) has shown promising results in clinical trials, but genetic engineering to high levels and in large scale remains challenging. We devised a sorting strategy that captures more than 90% of HSC activity in less than 10% of mobilized peripheral blood (mPB) CD34+ cells, and modeled a transplantation protocol based on highly purified, genetically engineered HSCs co-infused with uncultured progenitor cells. Prostaglandin E2 stimulation allowed near-complete transduction of HSCs with lentiviral vectors during a culture time of less than 38 hr, mitigating the negative impact of standard culture on progenitor cell function. Exploiting the pyrimidoindole derivative UM171, we show that transduced mPB CD34+CD38− cells with repopulating potential could be expanded ex vivo. Implementing these findings in clinical gene therapy protocols will improve the efficacy, safety, and sustainability of gene therapy and generate new opportunities in the field of gene editing. : In this article, Gentner and colleagues undertake a comprehensive strategy to advance ex vivo genetic engineering of HSCs for gene therapy. They experimentally define an optimal strategy to purify HSCs, which allows uncoupling long-term from short-term hematopoietic reconstitution, and implement ex vivo conditions that best preserve their biological properties applying novel transduction-enhancing compounds and pyrimidoindole derivatives to support HSC expansion. Keywords: HSC gene therapy, purified HSCs, HSC expansion, lentiviral vector transduction, prostaglandin E2, UM171
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- 2017
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15. Understanding and Tackling Immune Responses to Adeno-Associated Viral Vectors.
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Costa-Verdera, Helena, Unzu, Carmen, Valeri, Erika, Adriouch, Sahil, González Aseguinolaza, Gloria, Mingozzi, Federico, and Kajaste-Rudnitski, Anna
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- 2023
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16. Laboratory-Scale Lentiviral Vector Production and Purification for Enhanced Ex Vivo and In Vivo Genetic Engineering
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Alessio Cantore, Monica Soldi, Lucia Sergi Sergi, Thomas Kerzel, Anna Kajaste-Rudnitski, Paola Capasso, Luigi Naldini, Mario Leonardo Squadrito, Andrea Annoni, Ivan Cuccovillo, Giulia Unali, Mauro Biffi, Paola M.V. Rancoita, Angelo Lombardo, Soldi, Monica, Sergi Sergi, Lucia, Unali, Giulia, Kerzel, Thoma, Cuccovillo, Ivan, Capasso, Paola, Annoni, Andrea, Biffi, Mauro, Rancoita, Paola Maria Vittoria, Cantore, Alessio, Lombardo, Angelo, Naldini, Luigi, Squadrito, Mario Leonardo, and Kajaste-Rudnitski, Anna
- Subjects
0301 basic medicine ,lcsh:QH426-470 ,Genetic enhancement ,Viral vector ,Cell therapy ,03 medical and health sciences ,0302 clinical medicine ,Plasmid ,In vivo ,Genetics ,medicine ,Progenitor cell ,lcsh:QH573-671 ,innate immunity ,Molecular Biology ,Severe combined immunodeficiency ,Chemistry ,lcsh:Cytology ,Lentiviral vectors ,medicine.disease ,gene therapy ,hematopoietic stem cells ,3. Good health ,Cell biology ,manufacturing ,in vivo ,lcsh:Genetics ,030104 developmental biology ,030220 oncology & carcinogenesis ,ex vivo ,Molecular Medicine ,purification process ,Original Article ,Ex vivo - Abstract
Lentiviral vectors (LVs) are increasingly employed in gene and cell therapy. Standard laboratory production of LVs is not easily scalable, and research-grade LVs often contain contaminants that can interfere with downstream applications. Moreover, purified LV production pipelines have been developed mainly for costly, large-scale, clinical-grade settings. Therefore, a standardized and cost-effective process is still needed to obtain efficient, reproducible, and properly executed experimental studies and preclinical development of ex vivo and in vivo gene therapies, as high infectivity and limited adverse reactions are important factors potentially influencing experimental outcomes also in preclinical settings. We describe here an optimized laboratory-scale workflow whereby an LV-containing supernatant is purified and concentrated by sequential chromatographic steps, obtaining biologically active LVs with an infectious titer and specific activity in the order of 109 transducing unit (TU)/mL and 5 × 104 TU/ng of HIV Gag p24, respectively. The purification workflow removes >99% of the starting plasmid, DNA, and protein impurities, resulting in higher gene transfer and editing efficiency in severe combined immunodeficiency (SCID)-repopulating hematopoietic stem and progenitor cells (HSPCs) ex vivo, as well as reduced activation of inflammatory responses ex vivo and in vivo as compared to TU-matched, laboratory-grade vectors. Our results highlight the value of accessible purified LV production for experimental studies and preclinical testing., Graphical Abstract, Lentiviral vectors (LVs) are powerful gene-transfer tools routinely exploited for distinct research and clinical applications. LVs produced in most research laboratories contain contaminants that can generate confounding effects in experimental studies. Soldi et al. describe a laboratory-scale workflow for purified LV production, highlighting enhanced gene-editing efficiency and diminished inflammatory responses.
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- 2020
17. Constitutive IL-1RA production by modified immune cells protects against IL-1–mediated inflammatory disorders.
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Colantuoni, Mariasilvia, Jofra Hernandez, Raisa, Pettinato, Emanuela, Basso-Ricci, Luca, Magnani, Laura, Andolfi, Grazia, Rigamonti, Chiara, Finardi, Annamaria, Romeo, Valentina, Soldi, Monica, Sergi Sergi, Lucia, Rocchi, Martina, Scala, Serena, Hoffman, Hal M., Gregori, Silvia, Kajaste-Rudnitski, Anna, Sanvito, Francesca, Muzio, Luca, Naldini, Luigi, and Aiuti, Alessandro
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CRYOPYRIN-associated periodic syndromes ,PROGENITOR cells ,AUTOGRAFTS ,GENETIC transformation ,IMMUNOLOGIC diseases - Abstract
Dysregulation of the interleukin-1 (IL-1) pathway leads to immune diseases that can result in chronic tissue and organ inflammation. Although IL-1 blockade has shown promise in ameliorating these symptoms and improving patients' quality of life, there is an urgent need for more effective, long-lasting treatments. We developed a lentivirus (LV)–mediated gene transfer strategy using transplanted autologous hematopoietic stem/progenitor cells (HSPCs) as a source of IL-1 receptor antagonist (IL-1RA) for systemic delivery to tissues and organs. Transplantation of mouse and human HSPCs transduced with an IL-1RA–encoding LV ensured stable IL-1RA production while maintaining the clonogenic and differentiation capacities of HSPCs in vivo. We examined the efficacy of cell-mediated IL-1RA delivery in three models of IL-1–dependent inflammation, for which treatment hindered neutrophil recruitment in an inducible model of gout, prevented systemic and multi-tissue inflammation in a genetic model of cryopyrin-associated periodic syndromes, and reduced disease severity in an experimental autoimmune encephalomyelitis model of multiple sclerosis. Our findings demonstrate HSPC-mediated IL-1RA delivery as a potential therapeutic modality that can be exploited to suppress tissue and organ inflammation in diverse immune-related diseases involving IL-1–driven inflammation. Editor's summary: The IL-1 pathway is essential to fighting infection, but its dysregulation is associated with chronic inflammation in several autoinflammatory disorders. Colantuoni et al. developed a lentivirus (LV)–mediated gene transfer strategy with autologous hematopoietic stem/progenitor cells (HSPCs) that can be transplanted for systemic delivery of IL-1 receptor antagonist (IL-1RA). Mice transplanted with these LV-transduced HSPCs demonstrated ectopic expression of IL-1RA that was sufficient to prevent systemic and localized IL-1–mediated inflammation in murine models of neutrophil-mediated inflammation, cryopyrin-associated periodic syndrome, and experimental autoimmune encephalitis. This HSPC-based IL-1RA delivery method has the potential to be a viable alternative to current treatment options. —Christiana Fogg [ABSTRACT FROM AUTHOR]
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- 2023
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18. DNA damage contributes to neurotoxic inflammation in Aicardi-Goutières Syndrome astrocytes
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Anna Maria Sole Giordano, Marco Luciani, Francesca Gatto, Monah Abou Alezz, Chiara Beghè, Lucrezia Della Volpe, Alessandro Migliara, Sara Valsoni, Marco Genua, Monika Dzieciatkowska, Giacomo Frati, Julie Tahraoui-Bories, Silvia Clara Giliani, Simona Orcesi, Elisa Fazzi, Renato Ostuni, Angelo D’Alessandro, Raffaella Di Micco, Ivan Merelli, Angelo Lombardo, Martin A.M. Reijns, Natalia Gromak, Angela Gritti, and Anna Kajaste-Rudnitski
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Inflammation ,Autoimmune Diseases of the Nervous System ,Astrocytes ,DNA Damage ,Humans ,Nervous System Malformations ,Immunology ,Immunology and Allergy - Abstract
Aberrant induction of type I IFN is a hallmark of the inherited encephalopathy Aicardi-Goutières syndrome (AGS), but the mechanisms triggering disease in the human central nervous system (CNS) remain elusive. Here, we generated human models of AGS using genetically modified and patient-derived pluripotent stem cells harboring TREX1 or RNASEH2B loss-of-function alleles. Genome-wide transcriptomic analysis reveals that spontaneous proinflammatory activation in AGS astrocytes initiates signaling cascades impacting multiple CNS cell subsets analyzed at the single-cell level. We identify accumulating DNA damage, with elevated R-loop and micronuclei formation, as a driver of STING- and NLRP3-related inflammatory responses leading to the secretion of neurotoxic mediators. Importantly, pharmacological inhibition of proapoptotic or inflammatory cascades in AGS astrocytes prevents neurotoxicity without apparent impact on their increased type I IFN responses. Together, our work identifies DNA damage as a major driver of neurotoxic inflammation in AGS astrocytes, suggests a role for AGS gene products in R-loop homeostasis, and identifies common denominators of disease that can be targeted to prevent astrocyte-mediated neurotoxicity in AGS.
- Published
- 2022
19. Lentiviral vectors escape innate sensing but trigger p53 in human hematopoietic stem and progenitor cells
- Author
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Piras, Francesco, Riba, Michela, Petrillo, Carolina, Lazarevic, Dejan, Cuccovillo, Ivan, Bartolaccini, Sara, Stupka, Elia, Gentner, Bernhard, Cittaro, Davide, Naldini, Luigi, and Kajaste‐Rudnitski, Anna
- Published
- 2017
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20. HIV-1 envelope-dependent restriction of CXCR4-using viruses in child but not adult untransformed CD4+ T-lymphocyte lines
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Mariani, Samanta A., Brigida, Immacolata, Kajaste-Rudnitski, Anna, Ghezzi, Silvia, Rocchi, Alessia, Plebani, Anna, Vicenzi, Elisa, Aiuti, Alessandro, and Poli, Guido
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- 2012
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21. HIV-1 silencing mediated by TRIM22 inhibition of Sp1 binding to the promoter
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E. Vicenzi, F. Turrini, S.S. Marelli, A. Kajaste-Rudnitski, C. Van Lint, A.T. Das, B. Berkout, and G. Poli
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Microbiology ,QR1-502 ,Public aspects of medicine ,RA1-1270 - Published
- 2015
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22. Restriction factors of retroviral replication: the example of Tripartite Motif (TRIM) protein 5α and 22
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Kajaste-Rudnitski, Anna, Pultrone, Cinzia, Marzetta, Flavia, Ghezzi, Silvia, Coradin, Tiziana, and Vicenzi, Elisa
- Published
- 2010
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23. Assessing the Impact of Cyclosporin A on Lentiviral Transduction and Preservation of Human Hematopoietic Stem Cells in Clinically Relevant Ex Vivo Gene Therapy Settings
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Francesco Piras, Carolina Petrillo, Alessia Capotondo, Eugenio Montini, Andrea Calabria, Bernhard Gentner, Ivan Cuccovillo, Giulio Spinozzi, Anna Kajaste-Rudnitski, Luigi Naldini, Fabrizio Benedicenti, Alessandra Biffi, Petrillo, C., Calabria, A., Piras, F., Capotondo, A., Spinozzi, G., Cuccovillo, I., Benedicenti, F., Naldini, L., Montini, E., Biffi, A., Gentner, B., and Kajaste-Rudnitski, A.
- Subjects
Permissiveness ,engraftment and stemne ,Mice ,Transduction (genetics) ,0302 clinical medicine ,Transduction, Genetic ,Cyclosporin a ,Research Articles ,Mice, Knockout ,0303 health sciences ,Lentiviral transduction ,Cell Cycle ,Graft Survival ,Gene Transfer Techniques ,Hematopoietic Stem Cell Transplantation ,Chromosome Mapping ,Cell biology ,Haematopoiesis ,human hematopoietic stem cells ,engraftment and stemness ,lentiviral transduction ,transduction enhancers ,030220 oncology & carcinogenesis ,Cyclosporine ,Molecular Medicine ,Genetic Vector ,Stem cell ,Human ,Virus Integration ,Genetic Vectors ,Biology ,Lentiviru ,Viral vector ,Colony-Forming Units Assay ,03 medical and health sciences ,Genetics ,Animals ,Humans ,Progenitor cell ,human hematopoietic stem cell ,Molecular Biology ,Cell Proliferation ,030304 developmental biology ,Animal ,Lentivirus ,Hematopoietic Stem Cell ,Genetic Therapy ,Gene Transfer Technique ,Hematopoietic Stem Cells ,transduction enhancer - Abstract
Improving hematopoietic stem and progenitor cell (HSPC) permissiveness to lentiviral vector (LV) transduction without compromising their biological properties remains critical for broad-range implementation of gene therapy as a treatment option for several inherited diseases. This study demonstrates that the use of one-hit ex vivo LV transduction protocols based on either cyclosporin A (CsA) or rapamycin enable as efficient gene transfer as the current two-hit clinical standard into bone marrow–derived CD34+ cells while better preserving their engraftment capacity in vivo. CsA was additive with another enhancer of transduction, prostaglandin E2, suggesting that tailored enhancer combinations may be applied to overcome multiple blocks to transduction simultaneously in HSPC. Interestingly, besides enhancing LV transduction, CsA also significantly reduced HSPC proliferation, preserving the quiescent G0 fraction and the more primitive multipotent progenitors, thereby yielding the highest engraftment levels in vivo. Importantly, no alterations in the vector integration profiles could be detected between CsA and control transduced HSPC. Overall, the present findings contribute to the development of more efficient and sustainable LV gene therapy protocols, underscoring the benefits of scaling down required vector doses, as well as shortening the HSPC ex vivo culture time.
- Published
- 2019
24. Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer
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Fabio Russo, Giada Amodio, Anna Kajaste-Rudnitski, Grazia Andolfi, Michela Comi, Marta Fortunato, Francesca Romana Santoni de Sio, Laura Passeri, Silvia Gregori, and Luca Cesana
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lcsh:Immunologic diseases. Allergy ,Adoptive cell transfer ,immune tolerance ,T-Lymphocytes ,T cell ,Genetic Vectors ,Immunology ,Gene Expression ,Biology ,Monocytes ,Immunophenotyping ,Immune tolerance ,Viral vector ,Cell therapy ,Mice ,Immune system ,Transduction, Genetic ,medicine ,Animals ,Humans ,Immunology and Allergy ,dendritic cells ,Original Research ,Lentivirus ,Correction ,Interleukin-10 ,Cell biology ,allogeneic transplantation ,Interleukin 10 ,medicine.anatomical_structure ,Humanized mouse ,IL-10 ,Female ,cell therapy ,lcsh:RC581-607 - Abstract
The prominent role of dendritic cells (DC) in promoting tolerance and the development of methods to generate clinical grade products allowed the clinical application of tolerogenic DC (tolDC)-based therapies for controlling unwanted immune responses. We established an efficient method to generate tolerogenic human DC, producing supra-physiological levels of IL-10, by genetically engineering monocyte-derived DC with a bidirectional Lentiviral Vector (bdLV) encoding for IL-10 and a marker gene. DCIL−10 are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DCIL−10 in a humanized mouse model dampens allogeneic T cell recall responses, while murine DCIL−10 delays acute graft-vs.-host disease in mice. Our report outlines an efficient method to transduce human myeloid cells with large-size LV and shows that stable over-expression of IL-10 generates an effective cell product for future clinical applications in the contest of allogeneic transplantation.
- Published
- 2020
25. A variant in the CD209 promoter is associated with severity of dengue disease
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Sakuntabhai, Anavaj, Turbpaiboon, Chairat, Casadémont, Isabelle, Chuansumrit, Ampaiwan, Lowhnoo, Tassanee, Kajaste-Rudnitski, Anna, Kalayanarooj, Sita Mint, Tangnararatchakit, Kanchana, Tangthawornchaikul, Nattaya, Vasanawathana, Sirijit, Chaiyaratana, Wathanee, Yenchitsomanus, Pa-thai, Suriyaphol, Prapat, Avirutnan, Panisadee, Chokephaibulkit, Kulkanya, Matsuda, Fumihiko, Yoksan, Sutee, Jacob, Yves, Lathrop, G Mark, Malasit, Prida, Desprès, Philippe, and Julier, Cécile
- Published
- 2005
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26. Protocol to differentiate monolayer human induced pluripotent stem cells into inflammatory responsive astrocytes
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Giordano, Anna Maria Sole, Abou Alezz, Monah, Merelli, Ivan, and Kajaste-Rudnitski, Anna
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- 2023
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27. Pandemic vaccine preparedness--have we left something behind?
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Ilaria Capua, Anna Kajaste-Rudnitski, Elena Bertoli, and Elisa Vicenzi
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Published
- 2009
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28. Identification of TRIM22 single nucleotide polymorphisms associated with loss of inhibition of HIV-1 transcription and advanced HIV-1 disease
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Ghezzi, Silvia, Galli, Laura, Kajaste-Rudnitski, Anna, Turrini, Filippo, Marelli, Sara, Toniolo, Daniela, Casoli, Claudio, Riva, Agostino, Poli, Guido, Castagna, Antonella, and Vicenzi, Elisa
- Published
- 2013
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29. M1 polarization of human monocyte-derived macrophages restricts pre and postintegration steps of HIV-1 replication
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Cassetta, Luca, Kajaste-Rudnitski, Anna, Coradin, Tiziana, Saba, Elisa, Della Chiara, Giulia, Barbagallo, Marialuisa, Graziano, Francesca, Alfano, Massimo, Cassol, Edana, Vicenzi, Elisa, and Poli, Guido
- Published
- 2013
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30. Induction of protective antibody response by MF59-adjuvanted 2009 pandemic A/H1N1v influenza vaccine in HIV-1-infected individuals
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Kajaste-Rudnitski, Anna, Galli, Laura, Nozza, Silvia, Tambussi, Giuseppe, Di Pietro, Andrea, Pellicciotta, Gabriele, Monti, Alessandro, Mascagni, Paolo, Moro, Matteo, and Vicenzi, Elisa
- Published
- 2011
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31. A dimerizable cationic lipid with potential for gene delivery
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Candiani, Gabriele, Pezzoli, Daniele, Cabras, Mariasara, Ristori, Sandra, Pellegrini, Cinzia, Kajaste-Rudnitski, Anna, Vicenzi, Elisa, Sala, Carlo, and Zanda, Matteo
- Published
- 2008
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32. Efficient Ex Vivo Engineering and Expansion of Highly Purified Human Hematopoietic Stem and Progenitor Cell Populations for Gene Therapy
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Giuliana Ferrari, Luigi Naldini, Maria Rosa Lidonnici, Francesco Boccalatte, Erika Zonari, Anna Kajaste-Rudnitski, Bernhard Gentner, Giacomo Desantis, Alessandro Aiuti, Carolina Petrillo, Zonari, Erika, Desantis, Giacomo, Petrillo, Carolina, Boccalatte, Francesco E., Lidonnici, Maria Rosa, Kajaste Rudnitski, Anna, Aiuti, Alessandro, Ferrari, Giuliana, Naldini, Luigi, and Gentner, Bernhard
- Subjects
0301 basic medicine ,purified HSCs ,HSC expansion ,Genetic enhancement ,Antigens, CD38 ,Cell Culture Techniques ,CD34 ,Antigens, CD34 ,CD38 ,HSC gene therapy ,Biochemistry ,0302 clinical medicine ,Mice, Inbred NOD ,Transduction, Genetic ,lcsh:QH301-705.5 ,Cell Engineering ,lcsh:R5-920 ,Hematopoietic Stem Cell Transplantation ,Cell biology ,Haematopoiesis ,030220 oncology & carcinogenesis ,Genetic Vector ,Stem cell ,lcsh:Medicine (General) ,Cell Culture Technique ,Human ,Genetic Vectors ,Biology ,Article ,Lentiviru ,03 medical and health sciences ,Genetic ,Genetics ,Animals ,Humans ,Progenitor cell ,Cell Proliferation ,prostaglandin E2 ,Animal ,Lentivirus ,Hematopoietic Stem Cell ,Genetic Therapy ,Cell Biology ,Hematopoietic Stem Cells ,ADP-ribosyl Cyclase 1 ,Molecular biology ,Transplantation ,030104 developmental biology ,lcsh:Biology (General) ,UM171 ,lentiviral vector transduction ,purified HSC ,Ex vivo ,Developmental Biology - Abstract
Summary Ex vivo gene therapy based on CD34+ hematopoietic stem cells (HSCs) has shown promising results in clinical trials, but genetic engineering to high levels and in large scale remains challenging. We devised a sorting strategy that captures more than 90% of HSC activity in less than 10% of mobilized peripheral blood (mPB) CD34+ cells, and modeled a transplantation protocol based on highly purified, genetically engineered HSCs co-infused with uncultured progenitor cells. Prostaglandin E2 stimulation allowed near-complete transduction of HSCs with lentiviral vectors during a culture time of less than 38 hr, mitigating the negative impact of standard culture on progenitor cell function. Exploiting the pyrimidoindole derivative UM171, we show that transduced mPB CD34+CD38− cells with repopulating potential could be expanded ex vivo. Implementing these findings in clinical gene therapy protocols will improve the efficacy, safety, and sustainability of gene therapy and generate new opportunities in the field of gene editing., Highlights • CD34+CD38− cells as an HSC-enriched starting population for ex vivo gene therapy • Reduced culture time (, In this article, Gentner and colleagues undertake a comprehensive strategy to advance ex vivo genetic engineering of HSCs for gene therapy. They experimentally define an optimal strategy to purify HSCs, which allows uncoupling long-term from short-term hematopoietic reconstitution, and implement ex vivo conditions that best preserve their biological properties applying novel transduction-enhancing compounds and pyrimidoindole derivatives to support HSC expansion.
- Published
- 2017
33. Lentiviral vectors escape innate sensing but trigger p53 in human hematopoietic stem and progenitor cells
- Author
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Bernhard Gentner, Luigi Naldini, Dejan Lazarevic, Sara Bartolaccini, Michela Riba, Francesco Piras, Davide Cittaro, Anna Kajaste-Rudnitski, Carolina Petrillo, Ivan Cuccovillo, Elia Stupka, Piras, Francesco, Riba, Michela, Petrillo, Carolina, Lazarevic, Dejan, Cuccovillo, Ivan, Bartolaccini, Sara, Stupka, Elia, Gentner, Bernhard, Cittaro, Davide, Naldini, Luigi, and Kajaste rudnitski, Anna
- Subjects
0301 basic medicine ,Genetic enhancement ,hematopoietic stem and progenitor cells ,Genetic Vectors ,Cell ,lentiviral vectors ,Biology ,Viral vector ,Mice ,03 medical and health sciences ,Transduction (genetics) ,medicine ,innate sensing ,Animals ,Humans ,Progenitor cell ,Research Articles ,Innate immune system ,Lentivirus ,lentiviral vector ,Hematopoietic Stem Cell Transplantation ,Genetic Therapy ,Hematopoietic Stem Cells ,gene therapy ,Immunity, Innate ,Cell biology ,p53 signaling ,hematopoietic stem and progenitor cell ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Apoptosis ,Immunology ,Molecular Medicine ,Genetics, Gene Therapy & Genetic Disease ,Tumor Suppressor Protein p53 ,Haematology ,Research Article - Abstract
Clinical application of lentiviral vector (LV)‐based hematopoietic stem and progenitor cells (HSPC) gene therapy is rapidly becoming a reality. Nevertheless, LV‐mediated signaling and its potential functional consequences on HSPC biology remain poorly understood. We unravel here a remarkably limited impact of LV on the HSPC transcriptional landscape. LV escaped innate immune sensing that instead led to robust IFN responses upon transduction with a gamma‐retroviral vector. However, reverse‐transcribed LV DNA did trigger p53 signaling, activated also by non‐integrating Adeno‐associated vector, ultimately leading to lower cell recovery ex vivo and engraftment in vivo . These effects were more pronounced in the short‐term repopulating cells while long‐term HSC frequencies remained unaffected. Blocking LV‐induced signaling partially rescued both apoptosis and engraftment, highlighting a novel strategy to further dampen the impact of ex vivo gene transfer on HSPC. Overall, our results shed light on viral vector sensing in HSPC and provide critical insight for the development of more stealth gene therapy strategies.
- Published
- 2017
34. Cellular innate immunity and restriction of viral infection: implications for lentiviral gene therapy in human hematopoietic cells
- Author
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Kajaste Rudnitski A, NALDINI , LUIGI, Kajaste Rudnitski, A, and Naldini, Luigi
- Published
- 2015
35. Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer.
- Author
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Comi, Michela, Amodio, Giada, Passeri, Laura, Fortunato, Marta, Santoni de Sio, Francesca Romana, Andolfi, Grazia, Kajaste-Rudnitski, Anna, Russo, Fabio, Cesana, Luca, and Gregori, Silvia
- Subjects
DENDRITIC cells ,GENETIC transformation ,SUPPRESSOR cells ,T cells ,MOUSE diseases - Abstract
The prominent role of dendritic cells (DC) in promoting tolerance and the development of methods to generate clinical grade products allowed the clinical application of tolerogenic DC (tolDC)-based therapies for controlling unwanted immune responses. We established an efficient method to generate tolerogenic human DC, producing supra-physiological levels of IL-10, by genetically engineering monocyte-derived DC with a bidirectional Lentiviral Vector (bdLV) encoding for IL-10 and a marker gene. DC
IL−10 are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DCIL−10 in a humanized mouse model dampens allogeneic T cell recall responses, while murine DCIL−10 delays acute graft-vs.-host disease in mice. Our report outlines an efficient method to transduce human myeloid cells with large-size LV and shows that stable over-expression of IL-10 generates an effective cell product for future clinical applications in the contest of allogeneic transplantation. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
36. HIV-1 silencing mediated by TRIM22 inhibition of Sp1 binding to the promoter
- Author
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Elisa Vicenzi, Filippo Turrini, Atze T. Das, Sara Marelli, Anna Kajaste-Rudnitski, Ben Berkhout, Guido Poli, and Carine Van Lint
- Subjects
Epidemiology ,Immunology ,Public Health, Environmental and Occupational Health ,Human immunodeficiency virus (HIV) ,Biology ,TRIM22 ,medicine.disease_cause ,Virology ,Microbiology ,QR1-502 ,Infectious Diseases ,medicine ,Gene silencing ,Public aspects of medicine ,RA1-1270 - Published
- 2015
37. Towards improved yet regulated gene therapy for X-CGD
- Author
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Kajaste-Rudnitski, Anna and Aiuti, Alessandro
- Published
- 2023
- Full Text
- View/download PDF
38. Assessing the Impact of Cyclosporin A on Lentiviral Transduction and Preservation of Human Hematopoietic Stem Cells in Clinically Relevant Ex Vivo Gene Therapy Settings.
- Author
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Petrillo, Carolina, Calabria, Andrea, Piras, Francesco, Capotondo, Alessia, Spinozzi, Giulio, Cuccovillo, Ivan, Benedicenti, Fabrizio, Naldini, Luigi, Montini, Eugenio, Biffi, Alessandra, Gentner, Bernhard, and Kajaste-Rudnitski, Anna
- Published
- 2019
- Full Text
- View/download PDF
39. A variant in the CD209 promoter is associated with severity of dengue disease
- Author
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Kanchana Tangnararatchakit, Wathanee Chaiyaratana, Pa-thai Yenchitsomanus, Yves Jacob, Sita Mint Kalayanarooj, Nattaya Tangthawornchaikul, Prapat Suriyaphol, Chairat Turbpaiboon, Prida Malasit, Cécile Julier, Sirijit Vasanawathana, Ampaiwan Chuansumrit, G. Mark Lathrop, Panisadee Avirutnan, Fumihiko Matsuda, Anavaj Sakuntabhai, Kulkanya Chokephaibulkit, Sutee Yoksan, Philippe Desprès, Isabelle Casademont, Tassanee Lowhnoo, Anna Kajaste-Rudnitski, Génétique des Maladies Infectieuses et Autoimmunes, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medicine, Faculty of Medicine, Mahidol University [Bangkok]-Ramathibodi Hospital, Department of Biochemistry, Faculty of Science, Department of Pediatrics, Faculty of Medicine, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Research Center, Faculty of Medicine, Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur [Paris] (IP), Medical Molecular biology Unit, Faculty of Medicine, Mahidol University [Bangkok]-Siriraj Hospital, Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology BIOTEC-National Science and Technology Development Agency [Bangkok] (NSTDA), Department of Pediatrics, Khon Kaen Hospital-Ministry of Public Health, Department of Pediatrics, Faculty of Medecine, Center for Vaccine Development, Mahidol University [Bangkok]-Institute of Science and Technology for Research and Development, Génétique, Papillomavirus et Cancer Humain, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]
- Subjects
Population ,Receptors, Cell Surface ,MESH: Dengue ,Dengue virus ,medicine.disease_cause ,Severity of Illness Index ,Virus ,Article ,Dengue fever ,Dengue ,03 medical and health sciences ,Flaviviridae ,0302 clinical medicine ,MESH: Severity of Illness Index ,MESH: Polymorphism, Genetic ,Genetics ,medicine ,Humans ,Lectins, C-Type ,education ,Promoter Regions, Genetic ,MESH: Receptors, Cell Surface ,0303 health sciences ,education.field_of_study ,MESH: Humans ,Polymorphism, Genetic ,biology ,030306 microbiology ,Odds ratio ,biology.organism_classification ,medicine.disease ,Virology ,3. Good health ,MESH: Promoter Regions (Genetics) ,Flavivirus ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Immunology ,MESH: Cell Adhesion Molecules ,Viral disease ,Cell Adhesion Molecules ,MESH: Lectins, C-Type ,030215 immunology - Abstract
Dengue fever and dengue hemorrhagic fever are mosquito-borne viral diseases. Dendritic cell–specific ICAM-3 grabbing nonintegrin (DC-SIGN1, encoded by CD209), an attachment receptor of dengue virus, is essential for productive infection of dendritic cells1,2. Here, we report strong association between a promoter variant of CD209, DCSIGN1-336, and risk of dengue fever compared with dengue hemorrhagic fever or population controls. The G allele of the variant DCSIGN1-336 was associated with strong protection against dengue fever in three independent cohorts from Thailand, with a carrier frequency of 4.7% in individuals with dengue fever compared with 22.4% in individuals with dengue hemorrhagic fever (odds ratio for risk of dengue hemorrhagic fever versus dengue fever: 5.84, P = 1.4 × 10−7) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 × 10−6). This variant affects an Sp1-like binding site and transcriptional activity in vitro. These results indicate that CD209 has a crucial role in dengue pathogenesis, which discriminates between severe dengue fever and dengue hemorrhagic fever. This may have consequences for therapeutic and preventive strategies. Supplementary information The online version of this article (doi:10.1038/ng1550) contains supplementary material, which is available to authorized users.
- Published
- 2005
40. Inhibition of herpes simplex virus types 1 and 2 in vitro infection by sulfated derivatives of Escherichia coli K5 polysaccharide
- Author
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Tiziana Coradin, Debora Pinna, Elisa Vicenzi, Giorgio Zoppetti, Roberto Manservigi, Rafaela Argnani, Anna Kajaste-Rudnitski, Pasqua Oreste, Silvia Ghezzi, Guido Poli, Antonella Rotola, Pinna, Debora, Oreste, Pasqua, Coradin, Tiziana, Kajaste Rudnitski, Anna, Ghezzi, Silvia, Zoppetti, Giorgio, Rotola, Antonella, Argnani, Rafaela, Poli, Guido, Manservigi, Roberto, and Vicenzi, Elisa
- Subjects
Sexually transmitted disease ,Sexual transmission ,HSV2 ,Herpesvirus 2, Human ,viruses ,HSV1 ,inhibition ,sulfated derivatives of K5 E.Coli polysaccharide ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Antiviral Agents ,Virus ,Herpesviridae ,Microbiology ,Cell Line, Tumor ,Chlorocebus aethiops ,Escherichia coli ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Vero Cells ,Bacterial Capsules ,Recombination, Genetic ,Pharmacology ,Sulfates ,Epithelial Cells ,Entry into host ,Virology ,Microbicides for sexually transmitted diseases ,Infectious Diseases ,Herpes simplex virus ,Vero cell - Abstract
Herpes simplex virus type 1 (HSV-1) and HSV-2 are neurotropic viruses and common human pathogens causing major public health problems such as genital herpes, a sexually transmitted disease also correlated with increased transmission and replication of human immunodeficiency virus type 1 (HIV-1). Therefore, compounds capable of blocking HIV-1, HSV-1, and HSV-2 transmission represent candidate microbicides with a potential added value over that of molecules acting selectively against either infection. We report here that sulfated derivatives of the Escherichia coli K5 polysaccharide, structurally highly similar to heparin and previously shown to inhibit HIV-1 entry and replication in vitro, also exert suppressive activities against both HSV-1 and HSV-2 infections. In particular, the N,O-sulfated [K5-N,OS(H)] and O-sulfated epimerized [Epi-K5-OS(H)] forms inhibited the infection of Vero cells by HSV-1 and -2, with 50% inhibitory concentrations (IC 50 ) between 3 ± 0.05 and 48 ± 27 nM, and were not toxic to the cells at concentrations as high as 5 μM. These compounds impaired the early steps of HSV-1 and HSV-2 virion attachment and entry into host cells and reduced the cell-to-cell spread of HSV-2. Since K5-N,OS(H) and Epi-K5-OS(H) also inhibit HIV-1 infection, they may represent valid candidates for development as topical microbicides preventing sexual transmission of HIV-1, HSV-1, and HSV-2.
- Published
- 2008
41. TRIM22 Inhibits Influenza A Virus Infection by Targeting the Viral Nucleoprotein for Degradation
- Author
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Elisa Vicenzi, Greg J. Towers, Lucia Nicora, Andrea Di Pietro, Anna Kajaste-Rudnitski, Nadir Mechti, Alexandra Oteiza, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier (IRIM), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV]Life Sciences [q-bio] ,Immunology ,Alpha interferon ,Biology ,medicine.disease_cause ,TRIM22 ,Virus Replication ,Microbiology ,Virus ,Cell Line ,Small hairpin RNA ,Minor Histocompatibility Antigens ,Tripartite Motif Proteins ,03 medical and health sciences ,Dogs ,Virology ,Influenza A virus ,medicine ,Animals ,Humans ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,030306 microbiology ,RIG-I ,Gene Expression Profiling ,Viral Core Proteins ,RNA-Binding Proteins ,Epithelial Cells ,Nucleocapsid Proteins ,3. Good health ,Nucleoprotein ,Virus-Cell Interactions ,Up-Regulation ,Repressor Proteins ,Viral replication ,Gene Expression Regulation ,Insect Science ,Host-Pathogen Interactions ,Proteolysis - Abstract
Tripartite motif (TRIM) protein superfamily members are emerging as important effectors of the innate immune response against viral infections. In particular, TRIM22 was reported to exert antiviral activity against RNA viruses, such as hepatitis B virus (HBV), encephalomyocarditis virus (ECMV), and human immunodeficiency virus type 1 (HIV-1). We demonstrate here, for the first time, that TRIM22 is upregulated by influenza A virus (IAV) infection at both mRNA and protein levels in human alveolar epithelial A549 cells. Conversely, TRIM22 potently restricted IAV replication, in that prevention of TRIM22 expression by means of short hairpin RNA led to a 10-fold enhancement of IAV replication in these cells. Depletion of TRIM22 also reduced the anti-IAV activity of alpha interferon (IFN-α), suggesting that TRIM22 is an important IFN-stimulated gene that is required for maximal suppression of IAV by type I IFN. Furthermore, the IAV infectious titer decreased up to 100-fold in MDCK cells expressing exogenous human TRIM22. Restriction of IAV replication was accounted for by the interaction between TRIM22 and the viral nucleoprotein (NP), resulting in its polyubiquitination and degradation in a proteasome-dependent manner. Thus, TRIM22 represents a novel restriction factor upregulated upon IAV infection that curtails its replicative capacity in epithelial cells.
- Published
- 2013
42. Pandemic Vaccine Preparedness—Have We Left Something Behind?
- Author
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Elisa Vicenzi, Ilaria Capua, Anna Kajaste-Rudnitski, and Elena Bertoli
- Subjects
Change over time ,lcsh:Immunologic diseases. Allergy ,Adult ,Opinion ,Immunology ,Disaster Planning ,Biology ,Virology/Immune Evasion ,medicine.disease_cause ,Microbiology ,Haemagglutination inhibition ,Disease Outbreaks ,Influenza A Virus, H2N2 Subtype ,Seasonal influenza ,Birds ,Vaccine strain ,Influenza A Virus, H1N1 Subtype ,Virology ,Pandemic ,Influenza, Human ,Genetics ,Influenza A virus ,medicine ,Animals ,Humans ,Molecular Biology ,lcsh:QH301-705.5 ,Antigens, Viral ,Virology/Vaccines ,Viral Vaccine ,Influenza A Virus, H3N2 Subtype ,Hemagglutination Inhibition Tests ,Middle Aged ,lcsh:Biology (General) ,Influenza Vaccines ,Preparedness ,Influenza in Birds ,Parasitology ,lcsh:RC581-607 - Abstract
There are significant antigenic differences within subtypes that change over time as these viruses evolve, and this requires a semi-annual review and frequent update of vaccine strain candidates for human seasonal influenza vaccines. The degree of relatedness between the strains contained in the seasonal vaccine and the drifted strains that are isolated the following year is assessed through cross haemagglutination inhibition (HI) tests. If the results of these tests suggest that cross HI levels are low, the vaccine is updated to include the most recent strains. We reasoned that if a semi-annual review of the antigenic characteristics of human H1 and H3 viruses is necessary
- Published
- 2009
43. In vitro transfection of the U87-MG cell line with pTNF-α induces death of cancer vasculature
- Author
-
Pezzoli, D., Anna Kajaste-Rudnitski, Cabras, M., Pellegrini, C., Vicenzi, E., Zanda, M., and Candiani, G.
- Published
- 2008
44. Incremental Innovation of Ex Vivo Hematopoietic Stem Cell Engineering to Expand Clinical Gene Therapy Applications
- Author
-
Zonari, Erika, Desantis, Giacomo, Petrillo, Carolina, Meo, Oriana, Scaramuzza, Samantha, Lidonnici, Maria Rosa, Kajaste-Rudnitski, Anna, Ciceri, Fabio, Marktel, Sarah, Aiuti, Alessandro, Ferrari, Giuliana, Naldini, Luigi, and Gentner, Bernhard
- Published
- 2016
- Full Text
- View/download PDF
45. HIV-1 transcriptional silencing caused by TRIM22 inhibition of Sp1 binding to the viral promoter.
- Author
-
Turrini, Filippo, Marelli, Sara, Kajaste-Rudnitski, Anna, Lusic, Marina, Van Lint, Carine, Das, Atze T., Harwig, Alex, Berkhout, Ben, and Vicenzi, Elisa
- Subjects
INTRACELLULAR membranes ,HIV antibodies ,HIV infection risk factors ,GENE regulatory networks ,TRIM proteins - Abstract
Background: Intracellular defense proteins, also referred to as restriction factors, are capable of interfering with different steps of the viral life cycle. Among these, we have shown that Tripartite motif 22 (TRIM22) suppresses basal as well as phorbol ester-induced HIV-1 long terminal repeat (LTR)-mediated transcription, independently of its E3 ubiquitin ligase activity, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) binding to the U3 region and Tat interaction with the TAR region of the HIV-1 LTR. As basal HIV-1 transcription is driven by the transcription factor specificity protein 1 (Sp1), we have investigated whether TRIM22 could interfere with Sp1-driven transcriptional activation of the HIV-1 LTR. Findings: 293T cells, devoid of endogenous TRIM22 expression, were transfected with a TRIM22-expressing plasmid together with reporter plasmids driven by the HIV-1 LTR promoter either containing or lacking Sp1 binding sites or with reporter plasmids driven by non-viral promoter sequences either containing or lacking the three Sp1 binding sites from the HIV-1 LTR. These reporter assays showed that TRIM22 efficiently inhibited Sp1-driven transcription. Knocking down TRIM22 expression in the CD4
+ SupT1 T cell line increased the replication of Sp1-dependent HIV-1 variants. TRIM22 did not interact with Sp1, but prevented binding of Sp1 to the HIV-1 promoter, as demonstrated in protein-DNA pull down and chromatin immunoprecipitation assays. Conclusion: TRIM22 acts as a suppressor of basal HIV-1 LTR-driven transcription by preventing Sp1 binding to the HIV-1 promoter. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
46. Statistics of ice-structure interaction
- Author
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Kajaste-Rudnitski, Juri
- Published
- 1995
47. On dynamics of ice-structure interaction:Dissertation
- Author
-
Kajaste-Rudnitski, Juri
- Subjects
ice ,cold weather construction ,offshore structures ,crushing ,Greens function ,dynamics ,interactions ,Physics::Geophysics ,flexibility ,stochastic processes ,Astrophysics::Earth and Planetary Astrophysics ,elastic properties ,mathematical models ,Physics::Atmospheric and Oceanic Physics - Abstract
Ice-structure interaction is a complicated dynamic process of the failure of moving ice against an offshore structure often resulting in violent vibrations, thus endangering the normal exploitation operation. Beside the nonlinear ice crushing in the contact zone, the entire ice field behaviour as a part of the ice-structure system should be studied. In the process of ice-structure interaction, elastic waves propagate outwards from the contact area into the depth of a large moving ice sheet. These waves carry away a certain amount of energy. If the ice sheet is not infinite, the waves, reflected from the boundary, return and interfere on their way back towards the source with still outgoing waves. The ice sheet boundary conditions (finite or not) should be taken into account in any ice-structure interaction model. Actually the ice sheet presented as an elastic half-plane is subjected to the unit impulse force acting on its boundary edge. The method of potentials is used to find a Green function for a half-plane in the time domain. The convolution theorem enables one to extend this solution to the arbitrary force. The dynamic properties of the ice sheet are also studied in the frequency domain. The effect of the large (infinite) ice sheet may be described by its complex dynamic stiffness matrix and the notion of radiation damping is introduced. The stochastic approach to the problem is proposed next as an alternative to the direct material and interaction modelling. The structural response to spatially random excitation of ice crushing is studied. The notion of characteristic spatial dimensions of excitation is formulated and its effect on the structural response is examined as well. The quantitative relation between dominating ice crushing frequency, the ice sheet velocity and thickness, and the structural stiffness is found. This relation enables spectra of ice load to be established for various structures and ice environment on the basis of the available experimental or computed data. Having such a spectrum as an input excitation, the structural response can be easily found using the linear spectral analysis and the mode superposition methods, thus avoiding ice nonlinearities. Assuming an exponential correlation in space of the ice crushing forces, the spectral analysis can be applied to large structures.
- Published
- 1995
48. Numerical model of thermoelastic-plastic concrete material
- Author
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Kajaste-Rudnitski, Juri
- Subjects
construction materials ,hardening (materials) ,FEM ,numerical analysis ,concretes ,composite materials ,temperature ,finite element analysis ,fire resistance ,tension ,high strength concretes ,compressive strength ,computer programs ,models ,thermoelasticity ,tensile strength ,calculations ,fire tests ,structural analysis ,ABAQUS ,thermoplastics - Abstract
The objective of the employment of a sophisticated finite element method (FEM) program for structure fire resistance evaluation is to compliment, if not to substitute for altogether, the expensive fire tests of the natural size structural elements. Unfortunately the temperature dependent material options, provided by FEM programs, can be directly applied only to the steel and other materials with the similar hardening behaviour under compression and tension, For such materials as concrete with a hardening under compression and softening (cracking) under tension only cold numerical models exist and they cannot be used for the structure fire resistance evaluation. Instead the temperature dependent concrete model can be created in a separate subroutine and then inserted into the main program. Actually the thermoelastic-plastic concrete material was developed in two versions: first, the experimentally defined temperature functions of compressive and tensile strength. Young's modulus and thermoplastic (transient) strains were used as input data and then the standard thermoelastic stress analysis (ABAQUS) was performed. Second, the temperature dependent strength and Young's modulus were input as previously and the thermoplastic flow was computed in a subroutine following the ABAQUS algorithm for the compressive and tensile stress state taking into account the temperature dependence of the parameters involved. The computed results (displacements) were compared to the measured ones with resonable difference between.
- Published
- 1993
49. Analysis of structures under fire conditions
- Author
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Kajaste-Rudnitski, Juri
- Published
- 1992
50. Cellular Innate Immunity and Restriction of Viral Infection: Implications for Lentiviral Gene Therapy in Human Hematopoietic Cells.
- Author
-
Kajaste-Rudnitski, Anna and Naldini, Luigi
- Subjects
- *
GENE therapy , *HEMATOPOIETIC stem cells , *PROGENITOR cells , *VIRUS diseases , *ANTIVIRAL agents , *NATURAL immunity , *GENETICS - Abstract
Hematopoietic gene therapy has tremendous potential to treat human disease. Nevertheless, for gene therapy to be efficacious, effective gene transfer into target cells must be reached without inducing detrimental effects on their biological properties. This remains a great challenge for the field as high vector doses and prolonged ex vivo culture conditions are still required to reach significant transduction levels of clinically relevant human hematopoietic stem and progenitor cells (HSPCs), while other potential target cells such as primary macrophages can hardly be transduced. The reasons behind poor permissiveness of primary human hematopoietic cells to gene transfer partly reside in the retroviral origin of lentiviral vectors (LVs). In particular, host antiviral factors referred to as restriction factors targeting the retroviral life cycle can hamper LV transduction efficiency. Furthermore, LVs may activate innate immune sensors not only in differentiated hematopoietic cells but also in HSPCs, with potential consequences on transduction efficiency as well as their biological properties. Therefore, better understanding of the vector-host interactions in the context of hematopoietic gene transfer is important for the development of safer and more efficient gene therapy strategies. In this review, we briefly summarize the current knowledge regarding innate immune recognition of lentiviruses in primary human hematopoietic cells as well as discuss its relevance for LV-based ex vivo gene therapy approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
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