Imperial College London

ProfessorEricAlton

Faculty of MedicineNational Heart & Lung Institute

Chair in Gene Therapy
 
 
 
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Contact

 

+44 (0)20 7594 7929e.alton

 
 
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Assistant

 

Miss Samia Soussi +44 (0)20 7594 7980

 
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Location

 

Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

532 results found

Davies J, Morales S, Alton E, Martin Iet al., 2023, Lytic bacteriophage is a promising adjunct to common antibioticsacross cystic fibrosis clinical strains and culture models ofPseudomonas aeruginosa infection, Antibiotics, ISSN: 2079-6382

Journal article

Juarez-Molina C, Meng C, Morgan C, Padley S, Gill D, Hyde S, Alton EWFW, Griesenbach Uet al., 2022, Non-viral Gene Therapy for Autoimmune Pulmonary Alveolar Proteinosis, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A189-A189, ISSN: 1043-0342

Conference paper

Bell RV, Clarke NK, Alton EWFW, Griesenbach Uet al., 2022, Regulated expression of secreted transgenes by pulmonary transplanted macrophages in mice, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A55-A55, ISSN: 1043-0342

Conference paper

Sinadinos A, Bell R, Meng C, Gill DR, Hyde SC, Griesenbach U, Alton EWFWet al., 2022, A lentiviral vector intranasal dosing strategy to control local and systemic expression of intracellular and secreted transgenic proteins in vivo, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A195-A195, ISSN: 1043-0342

Conference paper

Richardson VR, Clarke NK, Griesenbach U, Alton EWFWet al., 2022, Optimising the genetic modification of macrophages using a lentiviral vector for application in cellular therapies, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A43-A43, ISSN: 1043-0342

Conference paper

Fiore MJ, Bell RV, Hickmott JW, Alton EWFW, Griesenbach Uet al., 2022, Significant transgene repression using the dCas9-KRAB-MeCP2 repressor system, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A151-A152, ISSN: 1043-0342

Conference paper

King JA, Cunanan A, Aziz S, Morant S, Murphy R, Coates N, Alton E, Guest C, Davies JCet al., 2022, PAWS FOR THOUGHT: SNIFFER DOGS FOR INFECTION SURVEILLANCE IN NON-SPUTUM PRODUCING PEOPLE WITH CF, Publisher: BMJ PUBLISHING GROUP, Pages: A21-A21, ISSN: 0040-6376

Conference paper

McLachlan G, Alton EWFW, Boyd AC, Clarke NKK, Davies JCC, Gill DRR, Griesenbach U, Hickmott JWW, Hyde S, Miah KMM, Molina CJet al., 2022, Progress in Respiratory Gene Therapy, HUMAN GENE THERAPY, Vol: 33, Pages: 893-912, ISSN: 1043-0342

Journal article

Alton E, Lund-Palau H, Juarez-Molina C, Meng C, Bhargava A, Pilou A, Aziz K, Clarke N, Atsumi N, Ashek A, Wilson M, Takata M, Padley S, Gill D, Hyde S, Morgan C, Griesenbach Uet al., 2022, Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression, Molecular Therapy - Methods and Clinical Development, Vol: 25, Pages: 382-391, ISSN: 2329-0501

We have developed a novel lentiviral vector, pseudotyped with the F and HN proteins from Sendai virus (rSIV.F/HN), which produces long-lasting, high efficiency transduction of the respiratory epithelium. Here, we addressed whether this platform technology can secrete sufficient levels of a therapeutic protein into the lung to ameliorate a fatal pulmonary disease, as an exemplar of its translational capability. Pulmonary Alveolar Proteinosis (PAP) results from alveolar GM-CSF insufficiency, resulting in abnormal surfactant homeostasis and consequent ventilatory problems. Lungs of GM-CSF knockout mice were transduced with a single dose of rSIV.F/HN expressing murine (m)GM-CSF (1e5-92e7 TU/mouse); mGM-CSF expression was dose-related and persisted for at least 11 months. PAP disease biomarkers were rapidly and persistently corrected, but we noted a narrow toxicity/efficacy window. rSIV.F/HN may be a useful platform technology to deliver therapeutic proteins for lung diseases requiring long-lasting and stable expression of secreted proteins.

Journal article

Bell R, Clarke NK, Isalan M, Alton EWFW, Griesenbach Uet al., 2022, Regulated Expression of LentiviralVectors Following Administration of anInducing Molecule, 2022 ASGCT Annual Meeting, Publisher: Cell Press, Pages: 419-419, ISSN: 1525-0016

Conference paper

Clarke NK, Sergijenko A, Pineault K, Sinadinos A, Meng C, Griesenbach U, Alton EWFWet al., 2022, Ex Vivo Transduced Macrophages Engraft in the Lung Following Transplantation and Produce Therapeutic Levels of Secreted Proteins, American Society of Cell and Gene Therapy, Publisher: CELL PRESS, Pages: 405-405, ISSN: 1525-0016

Conference paper

Hickmott JW, Prasertsuk P, Bell RV, Chan M, Griesenbach U, Alton EWFWet al., 2022, Heterologous Signal Peptides Enhance Protein Secretion for Respiratory Gene Therapy, Publisher: CELL PRESS, Pages: 417-418, ISSN: 1525-0016

Conference paper

Sergijenko A, Pineault KM, Moiseenko A, Gill DR, Hyde SC, Kreuz S, Alton EWFW, Griesenbach Uet al., 2022, Development of Molecular Assays to Determine Lentiviral Vector-Mediated Transduction Efficiency in Airway Epithelial Cells, Publisher: CELL PRESS, Pages: 419-419, ISSN: 1525-0016

Conference paper

Bell RV, Clarke NK, Isalan M, Alton EWFW, Griesenbach Uet al., 2022, Regulated Expression of Lentiviral Vectors Following Administration of an Inducing Molecule, Publisher: CELL PRESS, Pages: 419-419, ISSN: 1525-0016

Conference paper

Balachandar S, Graves TJ, Shimonty A, Kerr K, Kilner J, Xiao S, Slade R, Sroya M, Alikian M, Curetean E, Thomas E, McConnell VPM, McKee S, Boardman-Pretty F, Devereau A, Fowler TA, Caulfield MJ, Alton EW, Ferguson T, Redhead J, McKnight AJ, Thomas GA, Aldred MA, Shovlin CLet al., 2022, Identification and validation of a novel pathogenic variant in GDF2 (BMP9) responsible for hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations, American Journal of Medical Genetics Part A, Vol: 188, Pages: 959-964, ISSN: 0148-7299

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular dysplasia, characterized by arteriovenous malformations (AVMs), mucocutaneous telangiectasia and nosebleeds. HHT is caused by a heterozygous null allele in ACVRL1, ENG, or SMAD4, which encode proteins mediating bone morphogenetic protein (BMP) signaling. Several missense and stop-gain variants identified in GDF2 (encoding BMP9) have been reported to cause a vascular anomaly syndrome similar to HHT, however none of these patients met diagnostic criteria for HHT. HHT families from UK NHS Genomic Medicine Centres were recruited to the Genomics England 100,000 Genomes Project. Whole genome sequencing and tiering protocols identified a novel, heterozygous GDF2 sequence variant in all three affected members of one HHT family who had previously screened negative for ACVRL1, ENG, and SMAD4. All three had nosebleeds and typical HHT telangiectasia, and the proband also had severe pulmonary AVMs from childhood. In vitro studies showed the mutant construct expressed the proprotein but lacked active mature BMP9 dimer, suggesting the mutation disrupts correct cleavage of the protein. Plasma BMP9 levels in the patients were significantly lower than controls. In conclusion, we propose that this heterozygous GDF2 variant is a rare cause of HHT associated with pulmonary AVMs.

Journal article

Edmondson C, Westrupp N, Seddon P, Olden C, Wallis C, Dawson C, Brodlie M, Baxter F, McCormick J, MacFarlane S, Rice D, Macleod A, Brooker R, Connon M, Ghayyda S, Blaikie L, Thursfield R, Brown L, Price A, Fleischer E, Itterman J, Hughes D, Barrett P, Surette M, Donnelly C, Mateos-Corral D, Padley G, Wallenburg J, Brownlee K, Alton EWFW, Bush A, Davies JCet al., 2022, The feasibility of home monitoring of young people with cystic fibrosis: results from CLIMB-CF, Journal of Cystic Fibrosis, Vol: 21, Pages: 70-77, ISSN: 1569-1993

BACKGROUND: CF is traditionally assessed in clinic. It is unclear if home monitoring of young people with CF is feasible or acceptable. The COVID-19 pandemic has made home monitoring more of a necessity. We report the results of CLIMB-CF, exploring home monitoring's feasibility and potential obstacles. METHODS: We designed a mobile app and enrolled participants with CF aged 2-17 years and their parents for six months. They were asked to complete a variety of measures either daily or twice a week. During the study, participants and their parents completed questionnaires exploring depression, anxiety and quality of life. At the end of the study parents and participants completed acceptability questionnaires. RESULTS: 148 participants were recruited, 4 withdrew prior to starting the study. 82 participants were female with median (IQR) age 7.9 (5.2-12 years). Median data completeness was 40.1% (13.6-69.9%) for the whole cohort; when assessed by age participants aged ≥ 12 years contributed significantly less (15.6% [9.8-30%]). Data completeness decreased over time. There was no significant difference between parental depression and anxiety scores at the start and the end of the study nor in CFQ-R respiratory domain scores for participants ≥ 14 years. The majority of participants did not feel the introduction of home monitoring impacted their daily lives. CONCLUSIONS: Most participants felt home monitoring did not negatively impact their lives and it did not increase depression, anxiety or decrease quality of life. However, uptake was variable, and not well sustained. The teenage years pose a particular challenge and further work is required.

Journal article

Clarke N, Sinadinos A, Meng C, Alton E, Griesenbach Uet al., 2021, Ex vivo transduced macrophages produce therapeutic levels of secreted protein when transplanted to the lung, ESGCT Collaborative Virtual Congress, Publisher: Mary Ann Liebert, ISSN: 1043-0342

Conference paper

Bell R, Faulkner N, Griesenbach U, Alton EWFWet al., 2021, Intravenous administration of F/HN pseudotyped lentiviral vector, ESGCT Collaborative Virtual Congress, Publisher: Mary Ann Liebert, ISSN: 1043-0342

Conference paper

Bell RV, Isalan M, Alton EWFW, Griesenbach Uet al., 2021, Regulation of lentivirusā€mediated expression in a human airway model, ESGCT Collaborative Virtual Congress, Publisher: Mary Ann Liebert, ISSN: 1043-0342

Conference paper

, 2021, ESGCTCollaborative Virtual Congress19–22 October 2021Abstracts, Human Gene Therapy, Vol: 32, Pages: A1-A152, ISSN: 1043-0342

Journal article

Moiseenko A, Pineault K, Sergijenko A, Alton EWFW, Boyd AC, Davies JC, Gill DR, Griesenbach U, Hyde SC, McLachlan G, Hobbie S, Schuler M, Maier U, Thomas MU, Mennerich D, Kreuz Set al., 2021, Functional characterisation of an engineered next generation lentivirus vector for the treatment of cystic fibrosis, ESGCT Collaborative Virtual Congress, Publisher: MARY ANN LIEBERT, INC, Pages: A39-A39, ISSN: 1043-0342

Conference paper

Juarez-Molina CI, Lund-Palau H, Meng C, Gill D, Hyde S, Alton E, Griesenbach Uet al., 2021, Lentiviral vector/GM-CSF Gene Therapy for Autoimmune Pulmonary Alveolar Proteinosis, Publisher: MARY ANN LIEBERT, INC, Pages: A38-A38, ISSN: 1043-0342

Conference paper

Hickmott JW, Prasertsuk P, Bell RV, Chan M, Griesenbach U, Alton EWFWet al., 2021, Modifying signal peptides for respiratory gene therapy with secreted proteins, Publisher: MARY ANN LIEBERT, INC, Pages: A39-A40, ISSN: 1043-0342

Conference paper

Hickmott JW, Sinadinos AJ, Sergijenko A, Saleh AD, Nafchi NAM, Gamlen T, Gill DR, Hyde SC, Alton EWFW, Griesenbach Uet al., 2021, Single cell tools for measuring mRNA and protein expression for gene therapy, Publisher: MARY ANN LIEBERT, INC, Pages: A39-A39, ISSN: 1043-0342

Conference paper

Faulkner N, Alton EW, Griesenbach U, Kassiotis Get al., 2021, Reducing anti-vector humoral immunity through modulation of surface glycoprotein density, Publisher: MARY ANN LIEBERT, INC, Pages: A108-A109, ISSN: 1043-0342

Conference paper

Hickmott JW, Alton EWFW, Griesenbach U, Prasertsuk Pet al., 2021, Signal peptides

Patent

Juarez-Molina CI, Lund-Palau H, Meng C, Gill D, Hyde S, Alton E, Griesenbach Uet al., 2021, Gene Therapy for Autoimmune Pulmonary Alveolar Proteinosis, Publisher: CELL PRESS, Pages: 256-257, ISSN: 1525-0016

Conference paper

Clarke NK, Sinadinos A, Meng C, Alton EWFW, Griesenbach Uet al., 2021, Production of Recombinant Protein after Transplantation of Ex Vivo Transduced Macrophages, Publisher: CELL PRESS, Pages: 378-378, ISSN: 1525-0016

Conference paper

Bell RV, Faulkner N, Alton EWFW, Griesenbach Uet 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

Conference paper

Sergijenko A, Moiseenko A, Pineault K, Nafchi NAM, Chan M, Gamlen T, Gill DR, Hyde SC, Kreuz S, Griesenbach U, Alton EWFWet 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

Conference paper

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