D J Wells

Summary

Affiliation: Imperial College
Country: UK

Publications

  1. doi request reprint Gene doping: possibilities and practicalities
    Dominic 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
  2. pmc In silico characterisation and chromosomal localisation of human RRH (peropsin)--implications for opsin evolution
    James 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
  3. ncbi request reprint Opening the floodgates: clinically applicable hydrodynamic delivery of plasmid DNA to skeletal muscle
    Dominic J Wells
    Department of Cellular and Molecular Neuroscience, Imperial College London, UK
    Mol Ther 10:207-8. 2004
  4. pmc Gene doping: the hype and the reality
    D J Wells
    Department of Cellular and Molecular Neuroscience, Imperial College London, London, UK
    Br J Pharmacol 154:623-31. 2008
  5. doi request reprint Electroporation and ultrasound enhanced non-viral gene delivery in vitro and in vivo
    Dominic J Wells
    Department of Cellular and Molecular Neuroscience, Imperial College London, UK
    Cell Biol Toxicol 26:21-8. 2010
  6. doi request reprint Peptide-conjugated antisense therapy takes a skip ahead
    Dominic J Wells
    Department of Cellular and Molecular Neuroscience, Imperial College London, London, UK
    Mol Ther 16:1523-4. 2008
  7. ncbi request reprint Viral and non-viral methods for gene transfer into skeletal muscle
    Dominic 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
  8. ncbi request reprint Therapeutic restoration of dystrophin expression in Duchenne muscular dystrophy
    Dominic 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
  9. ncbi request reprint 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
  10. ncbi request reprint High-efficiency plasmid gene transfer into dystrophic muscle
    H 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

Collaborators

Detail Information

Publications42

  1. doi request reprint Gene doping: possibilities and practicalities
    Dominic 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...
  2. pmc In silico characterisation and chromosomal localisation of human RRH (peropsin)--implications for opsin evolution
    James 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...
  3. ncbi request reprint Opening the floodgates: clinically applicable hydrodynamic delivery of plasmid DNA to skeletal muscle
    Dominic J Wells
    Department of Cellular and Molecular Neuroscience, Imperial College London, UK
    Mol Ther 10:207-8. 2004
  4. pmc Gene doping: the hype and the reality
    D J Wells
    Department of Cellular and Molecular Neuroscience, Imperial College London, London, UK
    Br J Pharmacol 154:623-31. 2008
    ....
  5. doi request reprint Electroporation and ultrasound enhanced non-viral gene delivery in vitro and in vivo
    Dominic 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...
  6. doi request reprint Peptide-conjugated antisense therapy takes a skip ahead
    Dominic J Wells
    Department of Cellular and Molecular Neuroscience, Imperial College London, London, UK
    Mol Ther 16:1523-4. 2008
  7. ncbi request reprint Viral and non-viral methods for gene transfer into skeletal muscle
    Dominic 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
    ....
  8. ncbi request reprint Therapeutic restoration of dystrophin expression in Duchenne muscular dystrophy
    Dominic 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...
  9. ncbi request reprint 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...
  10. ncbi request reprint High-efficiency plasmid gene transfer into dystrophic muscle
    H 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...
  11. ncbi request reprint Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy
    D 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...
  12. ncbi request reprint Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase -- increased expression with reduced muscle damage
    J 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...
  13. ncbi request reprint Long-term expression of full-length human dystrophin in transgenic mdx mice expressing internally deleted human dystrophins
    A 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...
  14. ncbi request reprint Independent localization of dystrophin N- and C-terminal regions to the sarcolemma of mdx mouse myofibres in vivo
    M G Dunckley
    Department of Experimental Pathology, UMDS, Guy s Hospital, London, UK
    J Cell Sci 107:1469-75. 1994
    ....
  15. ncbi request reprint Enhanced in vivo delivery of antisense oligonucleotides to restore dystrophin expression in adult mdx mouse muscle
    K 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...
  16. ncbi request reprint Evaluation of plasmid DNA for in vivo gene therapy: factors affecting the number of transfected fibers
    D 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...
  17. doi request reprint Microbubble stability is a major determinant of the efficiency of ultrasound and microbubble mediated in vivo gene transfer
    Julia 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...
  18. doi request reprint Gene delivery to dystrophic muscle
    Kim 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...
  19. ncbi request reprint Relocalization of neuronal nitric oxide synthase (nNOS) as a marker for complete restoration of the dystrophin associated protein complex in skeletal muscle
    Kim 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
    ....
  20. ncbi request reprint Human dystrophin expression corrects the myopathic phenotype in transgenic mdx mice
    D 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...
  21. ncbi request reprint Characterisation of expression of mDMAHP, a homeodomain-encoding gene at the murine DM locus
    S 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...
  22. ncbi request reprint Gene therapy progress and prospects: electroporation and other physical methods
    D 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...
  23. ncbi request reprint Role of a 5'-enhancer in the transcriptional regulation of the human endothelial cell protein C receptor gene
    Luigina R Mollica
    Department of Haematology, Imperial College London, UK
    Blood 108:1251-9. 2006
    ....
  24. ncbi request reprint 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
    ....
  25. ncbi request reprint Electroporation for gene transfer to skeletal muscles: current status
    Jillian 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...
  26. pmc 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 study
    Maria Kinali
    The Dubowitz Neuromuscular Centre, University College London Institute of Child Health London, London, UK
    Lancet Neurol 8:918-28. 2009
    ....
  27. ncbi request reprint Zebrafish melanopsin: isolation, tissue localisation and phylogenetic position
    James 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...
  28. ncbi request reprint Immunological hurdles in the path to gene therapy for Duchenne muscular dystrophy
    Dominic 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...
  29. ncbi request reprint Expression of opsin genes early in ocular development of humans and mice
    Emma 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...
  30. ncbi request reprint Characterization of the role of gamma2 R531G mutation in AMP-activated protein kinase in cardiac hypertrophy and Wolff-Parkinson-White syndrome
    Joanna 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...
  31. doi request reprint Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression
    Paul 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...
  32. pmc Overexpression of heat shock protein 27 reduces cortical damage after cerebral ischemia
    Louise 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...
  33. ncbi request reprint 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...
  34. ncbi request reprint Stable micro-dystrophin gene transfer using an integrating adeno-retroviral hybrid vector ameliorates the dystrophic pathology in mdx mouse muscle
    Michael 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...
  35. ncbi request reprint Hsp27 overexpression in the R6/2 mouse model of Huntington's disease: chronic neurodegeneration does not induce Hsp27 activation
    Alexandra 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...
  36. ncbi request reprint 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...
  37. ncbi request reprint Cooperativity between far upstream enhancer and proximal promoter elements of the human {alpha}2(I) collagen (COL1A2) gene instructs tissue specificity in transgenic mice
    Shizuko 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...
  38. ncbi request reprint 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 mice
    Stewart 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...
  39. ncbi request reprint Identification of the key regions within the mouse pro-alpha 2(I) collagen gene far-upstream enhancer
    Sarah 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...
  40. ncbi request reprint Heat shock protein 27 protects the heart against myocardial infarction
    Christopher 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...
  41. ncbi request reprint The neuroprotective effects of heat shock protein 27 overexpression in transgenic animals against kainate-induced seizures and hippocampal cell death
    Mohammed 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
    ....
  42. ncbi request reprint The human ClC-4 protein, a member of the CLC chloride channel/transporter family, is localized to the endoplasmic reticulum by its N-terminus
    Hanneke 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...