Gene Therapy-System and applications

[aftabac]

Gene therapy - Systems and Applications

Tuesday, June 24, 2008 9:30 am - 5:00 pm

BioPark Hertfordshire
Broadwater Road
Welwyn Garden City, Hertfordshire AL7 3AX
United Kingdom


9:30 – 10:00 Registration
10:00 – 10:15 Introduction by the Chair: Professor Dominic Wells, Imperial College, London, UK
10:15 – 10:45 The use of morpholino antisense oligomers to modify gene expression
Professor Dominic Wells, Imperial College, London, UK
Morpholino antisense oligomers can be used to modify gene expression by blocking mRNA translation or altering splicing of the transcript. Examples of preclinical studies will be presented with particular emphasis on antisense directed exon skipping to restore the reading frame in the mRNA of the mdx mouse model of Duchenne muscular dystrophy (DMD). Antisense effects can be long-lasting (many months). The Phase I clinical trial undertaken in DMD patients by the UK MDEX Consortium using intramuscular delivery will be discussed. Methods of increasing the efficiency of systemic delivery will be considered including the use of diagnostic ultrasound.
10:45 – 11:15 “Dressing-up” naked plasmids: development of non-viral gene therapy vectors
Dr Dariusz C. Górecki, University of Portsmouth, UK
The clinical usefulness of non-viral methods is still hindered by their relatively low gene delivery/transgene expression efficiencies. Vectors must navigate a series of obstacles before the therapeutic gene can be expressed. In an attempt to increase plasmid DNA targeting we have developed and tested several novel gene delivery systems. Using these systems we have achieved a very significant increase in expression of a reporter gene in cells in vitro. More importantly, a 10-fold increase in the therapeutic gene expression in skeletal muscle of a mouse model of a human disease in vivo has been demonstrated.
11:15- 11:30 Speakers photo
11:30 – 12:00 Mid-morning break
12:00 – 12:30 Molecular imaging of gene transfer using the Na/I sylporter as a reporter gene: applications in gene therapy
Dr Georges Vassaux, Biotherapie Hepatique, France
12:30 – 13:00 Fetal and neonatal gene therapy
Dr Simon Waddington, University College London, UK
Fetal or neonatal gene therapy for monogenetic disorders could overcome major obstacles of intervention in the mature individual. Early gene transfer may prevent the onset of irreversible pathological changes, allow immunological tolerance to the introduced protein, take advantage of the high vector to cell ratio, and provide unique access to stem cell/progenitor compartments. The past few years have seen five studies showing long-term correction of monogenetic disorders by fetal gene transfer. Many others studies have examined the use of new vectors systems with therapeutic transgenes, tested their potential for treating diseases in a wide range of organs including the brain, lung and skin, and examined the hazards of fetal application.
13:00 – 13:10 Description of the Biopark facilities
13:10 – 14:30 Lunch
14:30 – 15:00 Gene therapy delivery of biologics for the treatment of arthritis
Dr David Gould, University of London, UK
15:00 – 15:30 Gene therapy in the cardiovascular system – applications and limitations
Professor Andrew Baker, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK
The ability to achieve therapeutic gain in models of cardiovascular disease is dictated by the choice of vector, the efficiency of gene delivery achieved and the chosen route of delivery of the therapeutic agent. There are many examples of pre-clinical successes including those relating to myocardial gene delivery, prevention of bypass graft failure and promotion of angiogenesis, although clinical translation of these technologies has thus far met with limited success. Deficiencies in gene delivery to cells of the cardiovascular system have been recognised as a major limitation for progress in gene therapy. For example, analysis of many adeno-associated virus (AAV) serotypes has revealed the poor transduction of both vascular smooth muscle cells and endothelial cells by many AAV serotypes, including AAV-2 through –8. For adenovirus (Ad) serotype 5 the expression and/or availability of the primary receptor CAR limits transduction. The tropism of viral vectors can be modified by a variety of techniques including capsid protein mutations, incorporation of targeting peptides into virions, use of targeting antibodies and vector pseudotyping. We have sought to engineer Ad and AAV vectors that are more efficient and selective for gene delivery to cardiovascular cells, with particular emphasis on endothelial and smooth muscle cells. These studies highlight the potential improvements that can be made to existing viral vectors to improve both the efficiency and selectivity of gene delivery to vascular cells in vitro and in vivo
15:30 – 16:00 Afternoon Tea/Coffee
16:00 – 16:30 Discussion
16:30- 17:00 Chairman’s summing up
18:00 Soiree at *The Best Western Homestead Court Hotel for all the participants
This meeting was organised by Euroscicon (www.euroscicon.com), a team of dedicated professionals working for the continuous improvement of technical knowledge transfer to all scientists. Euroscicon believe that they can make a positive difference to the quality of science by providing cutting edge information on new technological advancements to the scientific community. This is provided via our exceptional services to individual scientists, research institutions and industry. The event was hosted by 'BioPark’ (www.biopark.co.uk), a research and development centre in Welwyn Garden City providing specialist facilities and support for bioscience and health technology businesses to grow, and to develop new products and technologies
About the Chair
Professor Dominic Wells - Dr. Dominic (Nic) Wells qualified from Cambridge University as a veterinary surgeon in 1984. After several years in mixed general practice in Nottinghamshire he moved to the University of Wyoming to study comparative exercise physiology, writing his PhD on hummingbird flight energetics. He returned to the UK in 1990 as a temporary then full lecturer at the Royal Veterinary College . In 1995 he moved to the Charing Cross & Westminster Medical School , now part of the Medical Faculty of Imperial College London. Since 1990 he has worked on transgenic mice and the development of treatments for Duchenne muscular dystrophy.

About the Speakers
Dr Dariusz (Darek) C. Górecki, Gorecki qualified from the Medical School Warsaw as a medical doctor in 1986 and obtained his PhD in 1989. He has worked as Wellcome Trust Fellow at the Molecular Neurobiology Unit, Cambridge University and at the Royal Free and University College London where he studied the role of the dystrophin complex in the brain. In 2000 he moved to the School of Pharmacy and Biomedical Sciences, University of Portsmouth as a Senior Lecturer, then Reader and now he is Professor of Molecular
Medicine. He works on the pathogenesis of Duchenne muscular dystrophy and on the development of non-viral vectors for gene therapy
Georges Vassaux completed his BSc in Biochemistry in 1987 and his PhD in Molecular and Cellular Pharmacology in 1992 (University of Nice/Sophia-Antipolis, France).He has worked as a Post-Doctoral Research Fellow at Imperial College London from 1994 until 2000 where he essentially studied the control of gene expression in relation to gene therapy. In spring 2000 he was appointed Head of the Molecular Therapy laboratory in the Cancer Research UK (ex-ICRF) Molecular Oncology Unit at Hammersmith Hospital and in April 2007 he moved to a position at Inserm, Nantes, France. His current research interest is the use of Positron Emission Tomography to image gene expression in vivo to improve the efficacy of cancer gene therapy approaches.
Dr. Waddington was appointed as Senior Research Fellow by the Katherine Dormandy Trust in the Haemophilia Centre and Haemostasis Unit at the Royal Free & University College Medical School in August 2007. He leads a research team focused on preclinical application of gene and stem cell transfer technology, particularly for in utero and neonatal application for treatment of coagulopathies. He is also investigating the interaction between coagulation factors and adenoviruses in collaboration with Professor Andrew Baker (Glasgow) and Dr. John McVey (London).

Dr David Gould graduated with a degree in Pharmacolocy and obtained a PhD in Immunopharmacology from Southampton University. His main research interest is in the development of gene therapy for the treatment of rheumatoid arthritis. This work has entailed the development of regulated expression vectors that are controlled pharmacologically or that respond to environmental cues within the inflamed joint. To facilitate application of these regulated systems it has been necessary to prevent immune responses to the foreign proteins that are essential for their correct function
Professor Andrew Baker graduated from the University of London in 1990 with a First Class BSc (Joint Honours) in pharmacology and toxicology and then studied for his PhD with the Leukaemia Research Fund at the University of Wales College of Medicine, graduating in 1994. He then joined the group led by Professor Andrew Newby for his post-doctoral work in Cardiff and developed adenoviral vectors for gene delivery studies in the cardiovascular system. This was at the very early stages of gene therapy. Dr. Baker then transferred to a lectureship at the University of Bristol (Bristol Heart Institute) to continue studies on adenovirus-mediated gene transfer to assess vascular function in different model systems. At the same time he initiated his independent research programmes focusing on how to engineer delivery systems for optimal use in vivo in gene therapy applications. In 1999, Dr. Baker joined Professor Anna Dominiczak’s group at the University of Glasgow as a Senior Lecturer in Molecular Medicine, then as Reader and now as Professor of Molecular Medicine. He is based at the British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), which is a translational centre of excellence with a focus on primary and secondary prevention at cardiovascular disease


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