Publications
297 results found
Juarez-Molina CI, Lund-Palau H, Meng C, et al., 2021, Lentiviral vector/GM-CSF Gene Therapy for Autoimmune Pulmonary Alveolar Proteinosis, ESGCT Collaborative Virtual Congress, Publisher: MARY ANN LIEBERT, INC, Pages: A38-A38, ISSN: 1043-0342
Bell RV, Faulkner N, Alton EWFW, et al., 2021, Assessment of F/HN Pseudotyped Lentiviral Vector Following Intravenous Delivery to Mice, 24th Annual Meeting of the American Society of Gene & Cell Therapy, Publisher: CELL PRESS, Pages: 138-139, ISSN: 1525-0016
Clarke NK, Sinadinos A, Meng C, et al., 2021, Production of Recombinant Protein after Transplantation of Ex Vivo Transduced Macrophages, Publisher: CELL PRESS, Pages: 378-378, ISSN: 1525-0016
Pineault KM, Meng C, Alton EWFW, et al., 2021, Biosafety Risk Assessment: Biodistribution and Environmental Shedding of Topically Administered Lentiviral Vector to the Murine Airway, Publisher: CELL PRESS, Pages: 259-260, ISSN: 1525-0016
Sinadinos A, Pineault K, Saleh A, et al., 2021, Computational Tools for Airway-Image and Multidimensional-Data Analysis, Publisher: CELL PRESS, Pages: 257-257, ISSN: 1525-0016
Sinadinos A, Sergijenko A, Meng C, et al., 2021, Development of Lentiviral Vector Respiratory Tract Dosing Methods in Anticipation of Rodent GLP Toxicology Assessment, Publisher: CELL PRESS, Pages: 220-221, ISSN: 1525-0016
Hickmott JW, Prasertsuk P, Bell RV, et al., 2021, Towards Enhancing Signal Peptides for Respiratory Gene Therapy with Secreted Proteins, American Society of Gene and Cell Therapy, Publisher: CELL PRESS, Pages: 139-139, ISSN: 1525-0016
Sergijenko A, Moiseenko A, Pineault K, et al., 2021, Assessment of the Air-Liquid Interface Culture Model as a Tool to Validate Efficacy of a rSIV.F/HN-CFTR Vector, Publisher: CELL PRESS, Pages: 260-260, ISSN: 1525-0016
Juarez-Molina CI, Lund-Palau H, Meng C, et al., 2021, Gene Therapy for Autoimmune Pulmonary Alveolar Proteinosis, Publisher: CELL PRESS, Pages: 256-257, ISSN: 1525-0016
Sergijenko A, Moiseenko A, Pineault K, et al., 2021, LOW LEVELS OF LENTIVIRUS-MEDIATED CFTR GENE TRANSFER ARE SUFFICIENT TO GENERATE ION TRANSPORT CORRECTION IN AIR-LIQUID INTERFACE CULTURES FROM CYSTIC FIBROSIS PATIENTS, Publisher: BMJ PUBLISHING GROUP, Pages: A42-A42, ISSN: 0040-6376
Alton EWFW, Boyd AC, Davies JC, et al., 2021, TOWARDS A FIRST-IN-HUMAN TRIAL WITH A PSEUDOTYPED LENTIVIRUS, Publisher: BMJ PUBLISHING GROUP, Pages: A42-A42, ISSN: 0040-6376
Sinadinos A, Sergijenko A, Meng C, et al., 2021, DEVELOPMENT OF PROTOCOLS FOR MOUSE GLP-TOXICOLOGY STUDIES, Publisher: BMJ PUBLISHING GROUP, Pages: A32-A32, ISSN: 0040-6376
Sinadinos AJ, Sergijenko A, Saleh AD, et al., 2021, QUANTIFICATION OF MRNA AND PROTEIN FROM SINGLE CELLS FOR CYSTIC FIBROSIS GENE THERAPY, Publisher: BMJ PUBLISHING GROUP, Pages: A50-A50, ISSN: 0040-6376
Buning H, Baker AH, Griesenbach U, et al., 2021, In Vivo Gene Therapy for Canine SCID-X1 Using Cocal-Pseudotyped Lentiviral Vector, HUMAN GENE THERAPY, Vol: 32, Pages: 1-3, ISSN: 1043-0342
Sinadinos A, Sergijenko A, Saleh A, et al., 2020, SINGLE-CELL ASSAYS FOR QUANTIFYING MRNA AND PROTEIN DURING CYSTIC FIBROSIS GENE THERAPY TRIALS, North American Cystic Fibrosis Conference, Publisher: WILEY, Pages: S203-S203, ISSN: 8755-6863
Pineault KM, Meng C, Griesenbach U, et al., 2020, BIODISTRIBUTION AND ENVIRONMENTAL SHEDDING OF LENTIVIRAL VECTORS FOLLOWING TOPICAL ADMINISTRATION TO MURINE LUNGS, Publisher: WILEY, Pages: S240-S240, ISSN: 8755-6863
Alton EW, Boyd A, Davies JC, et al., 2020, TOWARDS A FIRST-IN-HUMAN TRIAL WITH A PSEUDOTYPED LENTIVIRUS, Publisher: WILEY, Pages: S224-S224, ISSN: 8755-6863
Sinadinos A, Sergijenko A, Meng C, et al., 2020, DEVELOPMENT OF PROTOCOLS FOR MOUSE GLP-TOXICOLOGY STUDIES, Publisher: WILEY, Pages: S196-S196, ISSN: 8755-6863
Sergijenko A, Moiseenko A, Pineault KM, et al., 2020, LOW LEVELS OF CFTR GENE TRANSFER WITH F/HN PSEUDOTYPED LENTIVIRUS ARE SUFFICIENT TO GENERATE ION TRANSPORT CORRECTION IN AIRWAY CELL CULTURES FROM CYSTIC FIBROSIS PATIENTS, Publisher: WILEY, Pages: S73-S73, ISSN: 8755-6863
Alton EWFW, Boyd AC, Davies JC, et al., 2020, Gene Therapy for Respiratory Diseases: Progress and a Changing Context, HUMAN GENE THERAPY, Vol: 31, Pages: 911-916, ISSN: 1043-0342
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Saleh AD, Durham SR, Shamji MH, et al., 2019, PEAK NASAL INSPIRATORY FLOW AND NASAL CYTOKINES ARE USEFUL BIOMARKERS OF NASAL INFLAMMATION IN CYSTIC FIBROSIS GENE THERAPY, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A13-A13, ISSN: 0040-6376
Saleh A, Griesenbach U, Alton E, et al., 2019, ASSAY DEVELOPMENT FOR A FIRST-IN-MAN LENTIVIRUS GENE THERAPY TRIAL FOR CYSTIC FIBROSIS, Publisher: WILEY, Pages: S358-S358, ISSN: 8755-6863
Bell RV, McKinnon TAJ, Alton EWFW, et al., 2019, Gene therapy for thrombotic thrombocytopaenic purpura, Annual Conference of the British Society for Gene and Cell Therapy, Publisher: Mary Ann Liebert, Pages: A14-A14, ISSN: 1043-0342
Thrombotic Thrombocytopaenic Purpura (TTP) is a rare (∼1/200,000 people) but life‐threatening disease caused by inherited or acquired deficiencies in ADAMTS13; a metalloprotease responsible for cleavage of large von Willebrand factor (VWF) multimers in the plasma. Reduced cleavage of thrombogenic VWF multimers through deficient ADAMTS13 can lead to spontaneous, wide‐spread accumulation of platelet‐rich thrombi. Without treatment, thrombi accumulation within the microvasculature causes organ failure and death in 90% of acute events. Individuals with TTP receive regular plasma infusions to restore ADAMTS13 levels. Despite current treatments reducing mortality rates, high treatment burden and morbidity associated with donor‐derived plasma warrants the development of a novel therapy for TTP. Gene therapy offers an alternative treatment which could prevent the onset of life‐threatening acute TTP episodes. The UK Cystic Fibrosis Gene Therapy Consortium, has developed a lentivirus pseudotyped with the Sendai virus envelope proteins F and HN for efficient lung gene transfer. Here, we assess whether lungs can be used as ‘factories’ for efficient and persistent ADAMTS13 production. We first cloned ADAMTS13 cDNA into a lentivirus producer plasmid and demonstrated proteolytic activity against VWF following co‐expression in HEK293T cells and subsequent detection of cleaved VWF by SDS‐PAGE. Vector is currently being manufactured using GMP‐compliant production methods. Next, ADAMTS13 knockout mice were characterised to determine suitable biomarkers (e.g. ADAMTS13 plasma levels and VWF cleavage activity) for assessing efficacy of pulmonary gene transfer. Future work will assess the restoration of plasma ADAMTS13 function in knockout mice and protection against TTP‐like symptoms.
Griesenbach U, 2019, Gene therapy for pulmonary disorders, Annual Conference of the British-Society-for-Gene-and-Cell-Therapy, Publisher: MARY ANN LIEBERT, INC, Pages: A4-A4, ISSN: 1043-0342
Palau H, Meng C, Bhargava A, et al., 2019, Lentivirus Gene Therapy for Autoimmune Pulmonary Alveolar Proteinosis, 22nd Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), Publisher: CELL PRESS, Pages: 43-44, ISSN: 1525-0016
Davies G, Griesenbach U, Alton E, et al., 2019, 53 - Molecular Therapies for Cystic Fibrosis, Kendig's Disorders of the Respiratory Tract in Children, Pages: 800-811.e3, ISBN: 9780323448871
This chapter describes the therapeutic strategies for cystic fibrosis which are based on targeting cystic fibrosis transmembrane conductance regulator (CFTR), either at the gene or protein level. We provide updates on small molecule CFTR modulators and gene therapy, focusing on clinical development and evaluation. The field has seen significant progress over recent years, particularly with the CFTR potentiator, ivacaftor, in patients with class III mutations. Increased understanding of the abnormalities in the structure and function of CFTR protein will help optimize the approaches required for normalizing function and, in doing so, aid the rational design of clinical trials-both in terms of the development of more efficacious drugs and the selection of appropriate patient populations. While progress with gene therapy remains some way behind, potential benefits (including being mutation agnostic and a nonsystemic route of delivery) remain significant. It may be that future optimal approaches will harness the benefits of more than one of these approaches and lead to considerable synergy. The ultimate goal for molecular and advanced therapies in cystic fibrosis is to find drugs or combinations of drugs capable of restoring CFTR function, applicable to patients with any genetic mutation.
Davies G, Griesenbach U, Alton E, et al., 2019, Molecular Therapies for Cystic Fibrosis, Kendig's Disorders of the Respiratory Tract in Children, Publisher: Elsevier, Pages: 800-811.e3
Lund-Palau H, Meng C, Pilou A, et al., 2018, LENTIVIRUS GM-CSF GENE THERAPY AMELIORATES AUTOIMMUNE PULMONARY ALVEOLAR PROTEINOSIS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A1-A2, ISSN: 0040-6376
Paul-Smith M, Pytel K, Gelinas J-F, et al., 2018, The murine lung as a factory to produce secreted intrapulmonary and circulatory proteins, Gene Therapy, Vol: 25, Pages: 345-358, ISSN: 0969-7128
We have shown that a lentiviral vector (rSIV.F/HN) pseudotyped with the F and HN proteins from Sendai virus generates high levels of intracellular proteins after lung transduction. Here, we evaluate the use of rSIV.F/HN for production of secreted proteins. We assessed whether rSIV.F/HN transduction of the lung generates therapeutically relevant levels of secreted proteins in the lung and systemic circulation using 1-anti-trypsin (hAAT) and factor VIII (hFVIII) as exemplars. Sedated mice were transduced with rSIV.F/HN carrying either the secreted reporter gene Gaussia luciferase (GLux) or the hAAT or hFVIII cDNAs by nasal sniffing.rSIV.F/HN-hAAT transduction lead to therapeutically relevant hAAT levels (70 g/ml) in ELF, with stable expression persisting for at least 19 months from a single application. Secreted proteins produced in the lung were released into the circulation and stable expression was detectable in blood. The levels of hFVIII in murine blood approached therapeutically relevant targets. rSIV.F/HN was also able to produce secreted hAAT and hFVIII in transduced human primary airway cells.rSIV.F/HN transduction of the murine lungs leads to long-lasting and therapeutically relevant levels of secreted proteins in the lung and systemic circulation. These data broaden the use of this vector platform for a large range of disease indications.
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