Research Topics
Genomes and Genes | D J WellsSummaryAffiliation: Imperial College Country: UK Publications
| Collaborators
|
Detail Information
Publications
Gene doping: possibilities and practicalitiesDominic J Wells
Gene Targeting Group, Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, London, UK
Med Sport Sci 54:166-75. 2009..Genetic manipulation in the context of athletic performance is commonly referred to as gene doping...
In silico characterisation and chromosomal localisation of human RRH (peropsin)--implications for opsin evolutionJames Bellingham
Gene Targeting Unit, Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College London, Charing Cross Hospital, St Dunstan s Road, London, W6 8RP, UK
BMC Genomics 4:3. 2003..Exceptions to this are RGR-opsin and melanopsin, whose genes have very different intron insertion positions. The gene structure of another opsin, peropsin (retinal pigment epithelium-derived rhodopsin homologue, RRH) is unknown...
Opening the floodgates: clinically applicable hydrodynamic delivery of plasmid DNA to skeletal muscleDominic J Wells
Department of Cellular and Molecular Neuroscience, Imperial College London, UK
Mol Ther 10:207-8. 2004
Gene doping: the hype and the realityD J Wells
Department of Cellular and Molecular Neuroscience, Imperial College London, London, UK
Br J Pharmacol 154:623-31. 2008....
Electroporation and ultrasound enhanced non-viral gene delivery in vitro and in vivoDominic J Wells
Department of Cellular and Molecular Neuroscience, Imperial College London, UK
Cell Biol Toxicol 26:21-8. 2010..This review provides an introduction to the methodology and summarises the range of cells and tissues that have been genetically modified using these techniques...
Peptide-conjugated antisense therapy takes a skip aheadDominic J Wells
Department of Cellular and Molecular Neuroscience, Imperial College London, London, UK
Mol Ther 16:1523-4. 2008
Viral and non-viral methods for gene transfer into skeletal muscleDominic J Wells
Imperial College London, Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Charing Cross Hospital, UK
Curr Opin Drug Discov Devel 9:163-8. 2006....
Therapeutic restoration of dystrophin expression in Duchenne muscular dystrophyDominic J Wells
Gene Targeting Group, Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Charing Cross Hospital, London, W6 8RP, UK
J Muscle Res Cell Motil 27:387-98. 2006..The pre-clinical results of the last 4 years have encouraged the development of clinical trials for all of the above...
What do animal models have to tell us regarding Duchenne muscular dystrophy?D J Wells
Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Charing Cross Hospital, UK
Acta Myol 24:172-80. 2005..However, there has been much debate about the merits of the different animal models, which will only be finally clear as we learn from the initial human clinical trials...
High-efficiency plasmid gene transfer into dystrophic muscleH Gollins
Gene Targeting Unit, Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Imperial College Faculty of Medicine, Charing Cross Hospital, London, UK
Gene Ther 10:504-12. 2003..The combined treatment of hyaluronidase and electrotransfer results in highly efficient gene transfer in dystrophic muscle with limited muscle damage...
Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophyD J Wells
Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK
Hum Mol Genet 4:1245-50. 1995..To the extent that data obtained in mouse studies are applicable to DMD, the virtual elimination of morphological and biochemical abnormalities in the mdx mouse supports the use of this cDNA in somatic gene therapy protocols for DMD...
Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase -- increased expression with reduced muscle damageJ M McMahon
Gene Targeting Unit, Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, UK
Gene Ther 8:1264-70. 2001..This combination treatment results in greatly enhanced levels of transfected muscle fibres without the increases in muscle damage associated with the electrotransfer process...
Long-term expression of full-length human dystrophin in transgenic mdx mice expressing internally deleted human dystrophinsA Ferrer
Gene Targeting Unit, Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Imperial College London, Charing Cross Hospital, London, UK
Gene Ther 11:884-93. 2004..These results suggest that the presence of revertant fibres may prevent the development of serious immune responses in patients undergoing dystrophin gene therapy...
Independent localization of dystrophin N- and C-terminal regions to the sarcolemma of mdx mouse myofibres in vivoM G Dunckley
Department of Experimental Pathology, UMDS, Guy s Hospital, London, UK
J Cell Sci 107:1469-75. 1994....
Enhanced in vivo delivery of antisense oligonucleotides to restore dystrophin expression in adult mdx mouse muscleK E Wells
Department of Neuromuscular Diseases, Imperial College London, Charing Cross Hospital, W6 8RP London, UK
FEBS Lett 552:145-9. 2003..Although expression was transient, many of the corrected fibres initially showed levels of dystrophin expression well above the 20% of endogenous previously shown to be necessary for phenotypic correction of the dystrophic phenotype...
Evaluation of plasmid DNA for in vivo gene therapy: factors affecting the number of transfected fibersD J Wells
Gene Targeting Unit, Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London W6 8RP, UK
J Pharm Sci 87:763-8. 1998..Importantly, the plasmid size (7-16 kb) did not affect the number of fibers expressing the transgene, in both normal and regenerating muscle...
Microbubble stability is a major determinant of the efficiency of ultrasound and microbubble mediated in vivo gene transferJulia Alter
Imaging Sciences Department, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, UK
Ultrasound Med Biol 35:976-84. 2009..These findings emphasize the importance of detailed investigations into the properties of microbubbles to allow the production of a microbubble specifically designed for optimum performance with MBGT...
Gene delivery to dystrophic muscleKim E Wells
Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College, London, United Kingdom
Methods Mol Biol 423:421-31. 2008..Although it is unlikely that the electrotransfer approach will be useful clinically, it is an important experimental tool, particularly in testing potential immune responses to gene transfer in the absence of vector proteins...
Relocalization of neuronal nitric oxide synthase (nNOS) as a marker for complete restoration of the dystrophin associated protein complex in skeletal muscleKim E Wells
Department of Neuromuscular Diseases, Imperial College Faculty of Medicine, Charing Cross Hospital, St Dunstan's Road, W6 8RP, London, UK
Neuromuscul Disord 13:21-31. 2003....
Human dystrophin expression corrects the myopathic phenotype in transgenic mdx miceD J Wells
Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK
Hum Mol Genet 1:35-40. 1992..The cDNA construct which is based on a very mild BMD phenotype thus encodes a highly functional dystrophin molecule whose reduced size renders it an attractive candidate for development as a therapeutic gene transfer reagent...
Characterisation of expression of mDMAHP, a homeodomain-encoding gene at the murine DM locusS K Heath
Department of Pharmacology, Charing Cross and Westminster Medical School, London, UK
Hum Mol Genet 6:651-7. 1997..8 kb compared with 3.5 kb) must be carefully considered...
Gene therapy progress and prospects: electroporation and other physical methodsD J Wells
Gene Targeting Unit, Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Psychological Medicine, Imperial College London, Charing Cross Hospital, St Dunstan's Road, London, UK
Gene Ther 11:1363-9. 2004..As plasmid DNA appears to be a safe gene vector system, it seems likely that plasmid with physically enhanced delivery will be used increasingly in clinical trials...
Role of a 5'-enhancer in the transcriptional regulation of the human endothelial cell protein C receptor geneLuigina R Mollica
Department of Haematology, Imperial College London, UK
Blood 108:1251-9. 2006....
Structure and evolution of the teleost extraretinal rod-like opsin (errlo) and ocular rod opsin (rho) genes: is teleost rho a retrogene?James Bellingham
Gene Targeting Unit, Department of Neuromuscular Diseases, Division of Neuroscience, Imperial College London, Charing Cross Hospital, St Dunstan s Road, London, W6 8RP, United Kingdom
J Exp Zool B Mol Dev Evol 297:1-10. 2003....
Electroporation for gene transfer to skeletal muscles: current statusJillian M McMahon
Gene Targeting Unit, Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College London, Charing Cross Hospital, London, UK
BioDrugs 18:155-65. 2004..As this electroporation-enhanced non-viral gene delivery system works well in larger species and avoids the vector-specific immune responses associated with recombinant viruses, the prospects for clinical application are promising...
Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept studyMaria Kinali
The Dubowitz Neuromuscular Centre, University College London Institute of Child Health London, London, UK
Lancet Neurol 8:918-28. 2009....
Zebrafish melanopsin: isolation, tissue localisation and phylogenetic positionJames Bellingham
Department of Integrative and Molecular Neuroscience, Imperial College Faculty of Medicine, Charing Cross Hospital, London, UK
Brain Res Mol Brain Res 107:128-36. 2002..They might represent a separate branch of photopigment evolution in the vertebrates or they may have a non-direct photosensory function, perhaps as a photoisomerase, in non-rod, non-cone light detection...
Immunological hurdles in the path to gene therapy for Duchenne muscular dystrophyDominic J Wells
Department of Neuromuscular Diseases, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Charing Cross Hospital, St Dunstan s Road, London, W6 8RP, UK
Expert Rev Mol Med 4:1-23. 2002..Although much work remains to be done, there are promising indications that these immune responses might not prove as much of a concern as originally envisaged...
Expression of opsin genes early in ocular development of humans and miceEmma E Tarttelin
Department of Integrative and Molecular Neuroscience, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College London, Charing Cross Hospital, St Dunstan s Road, London W6 8RP, UK
Exp Eye Res 76:393-6. 2003..Human non-rod, non-cone opsins are also all expressed early, by 8.6 weeks post-conception. The implications of these observations are discussed with regard to the possible functions of these opsins at early stages of ocular development...
Characterization of the role of gamma2 R531G mutation in AMP-activated protein kinase in cardiac hypertrophy and Wolff-Parkinson-White syndromeJoanna K Davies
Cellular Stress Group, Medical Research Council Clinical Sciences Centre, Hammersmith Campus, Imperial College London, London W12 ONN, UK
Am J Physiol Heart Circ Physiol 290:H1942-51. 2006..The subsequent decrease in AMPK activity provides a mechanism that may explain the development of cardiac hypertrophy in this model...
Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progressionPaul S Sharp
Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UK
Neurobiol Dis 30:42-55. 2008..This study provides further support for the therapeutic potential of HSPs in ALS and other motor neuron disorders...
Overexpression of heat shock protein 27 reduces cortical damage after cerebral ischemiaLouise van der Weerd
RCS Unit of Biophysics, Institute of Child Health, University College London, London, UK
J Cereb Blood Flow Metab 30:849-56. 2010..Our results provide support for the powerful neuroprotective effects of HSP27 in cerebral ischemia...
Gene transfer studies in animals: what do they really tell us about the prospects for gene therapy in DMD?Dominic J Wells
Gene Targeting Unit, Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College, Charing Cross Campus, St Dunstan s Road, London W6 8RP, UK
Neuromuscul Disord 12:S11-22. 2002..The other major concern relates to uncertainty over the efficiency of the different vectors in man, particularly as many patients are likely to have encountered the infectious forms of the viruses that are proposed as vectors...
Stable micro-dystrophin gene transfer using an integrating adeno-retroviral hybrid vector ameliorates the dystrophic pathology in mdx mouse muscleMichael L Roberts
Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway - University of London, Egham, Surrey TW20 0EX, UK
Hum Mol Genet 11:1719-30. 2002..Finally, using a novel PCR approach, we detected reverse-transcribed, integrated proviral sequences in TA muscle genomic DNA by 4 weeks post injection, the levels of which were found to increase after 3 months...
Hsp27 overexpression in the R6/2 mouse model of Huntington's disease: chronic neurodegeneration does not induce Hsp27 activationAlexandra Zourlidou
Department of Medical and Molecular Genetics, King s College London, School of Medicine, London SE1 9RT, UK
Hum Mol Genet 16:1078-90. 2007..Our study is the first to suggest a differential modulation of Hsp27 activation in vivo and, importantly, it illustrates the diverse effect of Hsp27 on acute versus chronic models of disease...
Identification of a repressor in the first intron of the human alpha2(I) collagen gene (COL1A2)Taras T Antoniv
Laboratory of Genetics and Organogenesis, Research Division of the Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York 10021, USA
J Biol Chem 280:35417-23. 2005..More generally, the study reiterated the existence of species-specific difference in the regulatory networks of the mammalian alpha2(I) collagen coding genes...
Cooperativity between far upstream enhancer and proximal promoter elements of the human {alpha}2(I) collagen (COL1A2) gene instructs tissue specificity in transgenic miceShizuko Tanaka
Laboratory of Genetics and Organogenesis, Research Division of the Hospital for Special Surgery, Weill Medical College of Cornell University, 535 East 70th Street, New York, NY 10021, USA
J Biol Chem 279:56024-31. 2004..This study thus reiterates the complex and highly combinatorial nature of the regulatory network governing COL1A2 transcription in vivo...
Adeno-associated virus vector gene transfer and sarcolemmal expression of a 144 kDa micro-dystrophin effectively restores the dystrophin-associated protein complex and inhibits myofibre degeneration in nude/mdx miceStewart A Fabb
Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway, University of London, Surrey TW20 0EX, UK
Hum Mol Genet 11:733-41. 2002..We have therefore shown that the current micro-dystrophin gene delivered in vivo using an AAV vector is not only capable of restoring sarcolemmal DAP complexes, but can also ameliorate dystrophic pathology at the cellular level...
Identification of the key regions within the mouse pro-alpha 2(I) collagen gene far-upstream enhancerSarah De Val
Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Campus, London W12 ONN, United Kingdom
J Biol Chem 277:9286-92. 2002..A 400-bp sequence located between -17.0 and -16.6 is also essential for the enhancer because its deletion results in increased susceptibility to the chromatin environment...
Heat shock protein 27 protects the heart against myocardial infarctionChristopher A Efthymiou
The Hatter Institute and Centre for Cardiology, Universitiy College London Hospitals and Medical School London, Grafton Way, London WC1E 6DB, UK
Basic Res Cardiol 99:392-4. 2004..Our results show for the first time that mice over expressing hsp27 (verified by Western blotting analysis) were found to be protected from lethal ischaemia/reperfusion injury compared to their negative littermates...
The neuroprotective effects of heat shock protein 27 overexpression in transgenic animals against kainate-induced seizures and hippocampal cell deathMohammed T Akbar
Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College, London, United Kingdom
J Biol Chem 278:19956-65. 2003....
The human ClC-4 protein, a member of the CLC chloride channel/transporter family, is localized to the endoplasmic reticulum by its N-terminusHanneke Okkenhaug
MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Rd, London W12 0NN, UK
FASEB J 20:2390-2. 2006..A stretch of amino acids, residues 14-63, at the N-terminus constitutes a novel motif both necessary and sufficient for targeting hClC-4 and other membrane proteins to the ER...
