Professor of Molecular Therapy
Gene Therapy for Lung diseases
As Co-Director of the Gene Medicine Research Group my research is focused on the application of gene therapy technologies to provide therapeutic interventions for human disease. During my post-doctoral research at Oxford I was the first to demonstrate that gene transfer could correct the Cystic Fibrosis defect in transgenic mice. This led to an extensive pre-clinical and clinical programme of gene therapy. Products developed in the Gene Medicine Research Group have been evaluated in four gene therapy clinical trials. The most recent was a phase IIb clinical study involving 136 participants that showed a clinically relevant improvement in lung function in those receiving gene therapy over those receiving a placebo treatment. I am one of the founding principal investigators of the UK Cystic Fibrosis Gene Therapy Consortium, a rolling research programme to realise a gene therapy for cystic fibrosis. The consortium is comprised of three UK research groups who have conducted CF gene therapy clinical studies: the Gene Medicine Research Group, University of Oxford; the Centre for Molecular Medicine and Roslin Institute, University of Edinburgh; and, the Department of Gene Therapy, National Heart & Lung Institute, Imperial College London. Collectively we have been at the forefront of respiratory gene therapy for over 20 years.
Current research is focused on the development of CpG-free non-viral gene transfer formulations; adeno-associated virus and lentiviral gene transfer vectors pseudotyped for efficient lung gene transfer and precise genome engineering to enhance vector production and performance. My particular expertise is in the design and assessment of viral and non-viral gene therapy vectors, transgene expression cassette design, CRISPR/Cas9 genome engineering, characterisation of aerosol properties for efficient lung delivery, and GMP compliant viral and non-viral vector production. I work with other organisations to improve the quality of gene therapy research. I have acted as specialist advisor on the clinical safety of gene therapy vectors to both the Department of Health's Gene Therapy Advisory Committee and the Committee on the Safety of Medicines, and have also advised the Department of Health on the procurement of gene transfer vectors. I am an editor of both the Journal of Gene Medicine and Nature Scientific Reports
Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.
Alton EWFW. et al, (2015), Lancet Respir Med, 3, 684 - 691
CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression.
Hyde SC. et al, (2008), Nat Biotechnol, 26, 549 - 551
Lentivirus Gene Therapy for Autoimmune Pulmonary Alveolar Proteinosis
Palau H. et al, (2019), MOLECULAR THERAPY, 27, 43 - 44
Lessons learned from lung and liver in-vivo gene therapy: implications for the future.
van Haasteren J. et al, (2018), Expert Opin Biol Ther, 18, 959 - 972
The murine lung as a factory to produce secreted intrapulmonary and circulatory proteins.
Paul-Smith MC. et al, (2018), Gene Ther, 25, 345 - 358
Author Correction: Assessment of selected media supplements to improve F/HN lentiviral vector production yields.
Gélinas J-F. et al, (2018), Sci Rep, 8
Multiple Inhibitory Factors Act in the Late Phase of HIV-1 Replication: a Systematic Review of the Literature.
Gélinas J-F. et al, (2018), Microbiol Mol Biol Rev, 82