Simon N Waddington

Summary

Affiliation: Imperial College
Country: UK

Publications

  1. pmc LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives
    Faisal A Al-Allaf
    Department of Medical Genetics, Faculty of Medicine, Umm Al Qura University, Al Abedia Campus, P, O, Box 715, Makkah 21955, Saudi Arabia
    Int Arch Med 3:36. 2010
  2. pmc Gene delivery of a mutant TGFβ3 reduces markers of scar tissue formation after cutaneous wounding
    Simon N Waddington
    Institute for Women s Health, University College London, London, UK
    Mol Ther 18:2104-11. 2010
  3. ncbi request reprint Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy
    Simon N Waddington
    Imperial College London, Gene Therapy Research Group, Section of Cell and Molecular Biology, Sir Alexander Fleming Bldg, Imperial College Road, London, SW7 2AZ, United Kingdom
    Blood 104:2714-21. 2004
  4. pmc Perinatal gene transfer to the liver
    Tristan R McKay
    William Harvey Research Institute, Queen Mary University of London, London, UK
    Curr Pharm Des 17:2528-41. 2011
  5. pmc AAV-mediated gene transfer in the perinatal period results in expression of FVII at levels that protect against fatal spontaneous hemorrhage
    Christopher Binny
    University College London Cancer Institute, London, UK
    Blood 119:957-66. 2012
  6. ncbi request reprint Codon optimization of human factor VIII cDNAs leads to high-level expression
    Natalie J Ward
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Blood 117:798-807. 2011
  7. doi request reprint Intravenous administration of AAV2/9 to the fetal and neonatal mouse leads to differential targeting of CNS cell types and extensive transduction of the nervous system
    Ahad A Rahim
    Gene Transfer Technology Group, Institute for Women s Health, University College London, 86 96 Chenies Mews, London, WC1E 6HX, UK
    FASEB J 25:3505-18. 2011
  8. ncbi request reprint Perinatal gene delivery to the CNS
    Ahad A Rahim
    Institute for Women s Health, University College London, 86 96 Chenies Mews, London, WCIE 6HX, UK
    Ther Deliv 2:483-91. 2011
  9. doi request reprint Choice of surrogate and physiological markers for prenatal gene therapy
    Juliette M K M Delhove
    Gene Transfer Technology Group, Institute for Women s Health, University College London, London, UK
    Methods Mol Biol 891:273-90. 2012
  10. pmc Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins
    Amit C Nathwani
    Department of Hematology, University College London Cancer Institute, London, UK
    Mol Ther 19:876-85. 2011

Detail Information

Publications39

  1. pmc LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives
    Faisal A Al-Allaf
    Department of Medical Genetics, Faculty of Medicine, Umm Al Qura University, Al Abedia Campus, P, O, Box 715, Makkah 21955, Saudi Arabia
    Int Arch Med 3:36. 2010
    ....
  2. pmc Gene delivery of a mutant TGFβ3 reduces markers of scar tissue formation after cutaneous wounding
    Simon N Waddington
    Institute for Women s Health, University College London, London, UK
    Mol Ther 18:2104-11. 2010
    ....
  3. ncbi request reprint Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy
    Simon N Waddington
    Imperial College London, Gene Therapy Research Group, Section of Cell and Molecular Biology, Sir Alexander Fleming Bldg, Imperial College Road, London, SW7 2AZ, United Kingdom
    Blood 104:2714-21. 2004
    ..No humoral or cellular immunity against the protein, elevation of serum liver enzymes, or vector spread to the germline or maternal circulation were detected...
  4. pmc Perinatal gene transfer to the liver
    Tristan R McKay
    William Harvey Research Institute, Queen Mary University of London, London, UK
    Curr Pharm Des 17:2528-41. 2011
    ..We conclude by assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer...
  5. pmc AAV-mediated gene transfer in the perinatal period results in expression of FVII at levels that protect against fatal spontaneous hemorrhage
    Christopher Binny
    University College London Cancer Institute, London, UK
    Blood 119:957-66. 2012
    ..2% of normal, which remained at therapeutic levels for a further 28 weeks without toxicity. Thus, perinatal AAV-mediated gene transfer shows promise for disorders with onset of pathology early after birth...
  6. ncbi request reprint Codon optimization of human factor VIII cDNAs leads to high-level expression
    Natalie J Ward
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Blood 117:798-807. 2011
    ..These significant findings demonstrate that shorter FVIII constructs that can be more easily accommodated in viral vectors can result in increased therapeutic efficacy and may deliver effective gene therapy for hemophilia A...
  7. doi request reprint Intravenous administration of AAV2/9 to the fetal and neonatal mouse leads to differential targeting of CNS cell types and extensive transduction of the nervous system
    Ahad A Rahim
    Gene Transfer Technology Group, Institute for Women s Health, University College London, 86 96 Chenies Mews, London, WC1E 6HX, UK
    FASEB J 25:3505-18. 2011
    ..Furthermore, it may provide a therapeutic strategy for treatment of early lethal genetic diseases, such as Gaucher disease, and for disabling neuropathies, such as preterm brain injury...
  8. ncbi request reprint Perinatal gene delivery to the CNS
    Ahad A Rahim
    Institute for Women s Health, University College London, 86 96 Chenies Mews, London, WCIE 6HX, UK
    Ther Deliv 2:483-91. 2011
    ..This article will focus on the use of perinatal gene delivery as a research tool and the potential it has to develop into a realistic therapy that can be translated to the clinic...
  9. doi request reprint Choice of surrogate and physiological markers for prenatal gene therapy
    Juliette M K M Delhove
    Gene Transfer Technology Group, Institute for Women s Health, University College London, London, UK
    Methods Mol Biol 891:273-90. 2012
    ..In addition a few short examples are provided for continual and endpoint analysis in different disease models including hemophilia, cystic fibrosis, ornithine transcarbamylase deficiency and Gaucher disease...
  10. pmc Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins
    Amit C Nathwani
    Department of Hematology, University College London Cancer Institute, London, UK
    Mol Ther 19:876-85. 2011
    ..Long-term biochemical, ultrasound imaging, and histologic follow-up of this large cohort of NHP revealed no toxicity. These data support further evaluation of this vector in hemophilia B patients...
  11. doi request reprint Monitoring for potential adverse effects of prenatal gene therapy: mouse models for developmental aberrations and inadvertent germ line transmission
    Charles Coutelle
    National Heart and Lung Institute, Molecular and Cellular Medicine Section, Imperial College London, London, UK
    Methods Mol Biol 891:329-40. 2012
    ..We also describe here the analysis procedures for detection of germ line mutations based on quantitative PCR (qPCR) by sperm-DNA analysis and breeding studies...
  12. doi request reprint Monitoring for potential adverse effects of prenatal gene therapy: use of large animal models with relevance to human application
    Vedanta Mehta
    Prenatal Cell and Gene Therapy Group, EGA Institute for Women s Health, University College London, London, UK
    Methods Mol Biol 891:291-328. 2012
    ..Finally, we describe methods to monitor events around birth and long-term neonatal follow-up that are important when considering human translation of this therapy...
  13. ncbi request reprint Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice
    Mike Themis
    Gene Therapy Research Group, Section of Cell and Molecular Biology, Imperial College London, UK
    Mol Ther 12:763-71. 2005
    ..This system may provide a highly sensitive model to investigate integrating vector safety prior to clinical application...
  14. ncbi request reprint Fetal gene transfer
    Simon N Waddington
    University College London, Department of Haematology, Haemophilia Centre and Haemostasis Unit, Royal Free and University College London Medical School, Rowland Hill Street, London, NW3 2PF, UK
    Curr Opin Mol Ther 9:432-8. 2007
    ..This review gives a comprehensive summary of the development of fetal gene transfer over the past few years...
  15. doi request reprint In utero gene transfer to the mouse nervous system
    Ahad A Rahim
    Institute for Women s Health, University College London, 86 96 Chenies Mews, London WC1E 6HX, UK
    Biochem Soc Trans 38:1489-93. 2010
    ..In the present article, we review perinatal gene transfer from both a therapeutic and technological perspective...
  16. ncbi request reprint Activator protein 1 is a key terminal mediator of inflammation-induced preterm labor in mice
    David A MacIntyre
    2Imperial College Parturition Research Group, Institute of Reproduction and Developmental Biology, Imperial College London, Hammersmith Campus, London, W12 0NN, UK
    FASEB J 28:2358-68. 2014
    ..MacIntyre, D. A., Lee, Y. S., Migale, R., Herbert, B. R., Waddington, S. N., Peebles, D., Hagberg, H., Johnson, M. R., Bennett, P. R. Activator protein 1 is a key terminal mediator of inflammation-induced preterm labor in mice. ..
  17. pmc Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver
    Amit C Nathwani
    Department of Haematology, University College London, 98 Chenies Mews, London, United Kingdom, WC1E 6HX
    Blood 107:2653-61. 2006
    ..Furthermore, AAV5-pseudotyped scAAV vectors mediated successful transduction in macaques with pre-existing immunity to AAV8. Hence, this novel vector represents an important advance for hemophilia B gene therapy...
  18. ncbi request reprint Stable gene transfer to muscle using non-integrating lentiviral vectors
    Luis Apolonia
    Molecular Immunology Unit, Institute of Child Health, London, UK
    Mol Ther 15:1947-54. 2007
    ..Finally, we show that NILV can be used for achieving highly effective gene transfer and expression in muscle in vivo...
  19. ncbi request reprint Targeting the respiratory muscles of fetal sheep for prenatal gene therapy for Duchenne muscular dystrophy
    Boaz Weisz
    Department of Obstetrics and Gynaecology, University College London, United Kingdom
    Am J Obstet Gynecol 193:1105-9. 2005
    ..Fetal gene therapy may correct the primary genetic defect. Our aim was to achieve expression of a reporter gene in the respiratory muscles of early gestation fetal sheep...
  20. doi request reprint Vector systems for prenatal gene therapy: choosing vectors for different applications
    Charles Coutelle
    National Heart and Lung Institute, Molecular and Cellular Medicine Section, Imperial College London, London, UK
    Methods Mol Biol 891:41-53. 2012
    ..It reviews the key characteristics of the four main gene therapy vector systems and gives examples for their successful application in prenatal gene therapy experiments...
  21. doi request reprint Development of S/MAR minicircles for enhanced and persistent transgene expression in the mouse liver
    Orestis Argyros
    Gene Therapy Research Group, Section of Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UK
    J Mol Med (Berl) 89:515-29. 2011
    ..These promising results demonstrate the utility of minimally sized S/MAR vectors for persistent, atoxic gene expression...
  22. ncbi request reprint Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse
    Jerry Chan
    Experimental Fetal Medicine Group, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London, United Kingdom
    Stem Cells 25:875-84. 2007
    ..Although the low-level of chimerism achieved is not curative for DMD, this approach may be useful in other severe mesenchymal or enzyme deficiency syndromes, where low-level protein expression may ameliorate disease pathology...
  23. doi request reprint The concept of prenatal gene therapy
    Charles Coutelle
    National Heart and Lung Institute, Molecular and Cellular Medicine Section, Imperial College London, London, UK
    Methods Mol Biol 891:1-7. 2012
    ..It also provides guidance to the range of conditions to which prenatal gene therapy may be applied and to the technical approaches, vectors, and societal/ethical considerations for this newly emerging field of Fetal Medicine...
  24. ncbi request reprint In utero gene therapy: current challenges and perspectives
    Simon N Waddington
    Gene Therapy Research Group, Sir Alexander Fleming Building, Imperial College, South Kensington, London SW7 2AZ, UK
    Mol Ther 11:661-76. 2005
    ..We will pay special attention to the strategies and vectors that are most likely to be used for this application and will speculate on their expected developments for the near future...
  25. pmc Desmin-regulated lentiviral vectors for skeletal muscle gene transfer
    Gillian E Talbot
    King s College London School of Medicine, Nuclear Biology Group, Department of Medical and Molecular Genetics, Guy s Hospital, London, UK
    Mol Ther 18:601-8. 2010
    ..DES also confers a more reproducible and tissue-specific transgene expression profile compared to CKM and is therefore a highly attractive regulatory element for use in muscle gene therapy vectors...
  26. ncbi request reprint Increased glucocerebrosidase (GBA) 2 activity in GBA1 deficient mice brains and in Gaucher leucocytes
    Derek G Burke
    Clinical and Molecular Genetics Unit, UCL Institute of Child Health and Chemical Pathology, Great Ormond Street Hospital, London, UK
    J Inherit Metab Dis 36:869-72. 2013
    ..Work is now required to ascertain whether GBA2 activity is a disease modifying factor in Gaucher disease and to identify the mechanism(s) responsible for triggering increased GBA2 activity in GBA1 deficiency states. ..
  27. doi request reprint Candidate diseases for prenatal gene therapy
    Anna L David
    Prenatal Cell and Gene Therapy Group, EGA Institute for Women s Health, University College London, London, UK
    Methods Mol Biol 891:9-39. 2012
    ..In this chapter, we describe some examples of the candidate diseases and discuss how a prenatal gene therapy approach might work...
  28. doi request reprint Activation and deactivation of periventricular white matter phagocytes during postnatal mouse development
    Mariya Hristova
    Department of Obstetrics and Gynecology, EGA Institute of Women s Health, University College London, London, United Kingdom
    Glia 58:11-28. 2010
    ..This presence of highly active and IGF1- and MCSF-expressing phagocytes in the neighborhood of vulnerable white matter could play an important role in the genesis of or protection against axonal damage in the fetus and premature neonate...
  29. ncbi request reprint In utero gene transfer of human factor IX to fetal mice can induce postnatal tolerance of the exogenous clotting factor
    Simon N Waddington
    Gene Therapy, Section of Cell and Molecular Biology, Imperial College School of Science, Technology and Medicine, London, United Kingdom
    Blood 101:1359-66. 2003
    ..In contrast, all adult mice that had not been treated prenatally showed a rapid loss of the injected hFIX and the development of high hFIX antibody levels, both clear manifestations of a strong immune reaction...
  30. ncbi request reprint Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype
    Nigel L Kennea
    Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London, UK
    Cell Cycle 8:1069-79. 2009
    ..Importantly, the process of in vivo differentiation occurred without cell fusion. These findings suggest that hfMSC may provide a potential source of oligodendrocytes for study and potential therapy...
  31. doi request reprint The cyclopentenone 15-deoxy-delta 12,14-prostaglandin J(2) delays lipopolysaccharide-induced preterm delivery and reduces mortality in the newborn mouse
    Grisha Pirianov
    Imperial College Parturition Research Group, Department of Reproductive Biology, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, UK
    Endocrinology 150:699-706. 2009
    ....
  32. doi request reprint The differentiation and engraftment potential of mouse hematopoietic stem cells is maintained after bio-electrospray
    Kerol Bartolovic
    Wolfson Centre for Gene Therapy, Molecular Immunology Unit, UCL Institute of Child Health, University College London, 30 Guilford Street, London, UK
    Analyst 135:157-64. 2010
    ..Our studies demonstrate that these bio-protocols have no obvious negative effects, thus indicating significant promise for utility in biological sciences and for a plethora of healthcare applications...
  33. pmc Exon skipping of hepatic APOB pre-mRNA with splice-switching oligonucleotides reduces LDL cholesterol in vivo
    Petra Disterer
    Institute for Liver and Digestive Health, UCL, London, UK
    Mol Ther 21:602-9. 2013
    ..Weekly treatments generated a sustained reduction in LDL cholesterol levels of 34-51% in these mice, superior to pravastatin in a head-to-head comparison. These results validate APO-skip SSOs as a candidate therapy for FH...
  34. pmc Mitochondria and quality control defects in a mouse model of Gaucher disease--links to Parkinson's disease
    Laura D Osellame
    Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK
    Cell Metab 17:941-53. 2013
    ..These data provide conclusive evidence for mitochondrial dysfunction in GD and provide insight into the pathogenesis of PD and PD-GBA...
  35. ncbi request reprint Delivery and long-term expression of a 135 kb LDLR genomic DNA locus in vivo by hydrodynamic tail vein injection
    Olivia C Hibbitt
    Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK
    J Gene Med 9:488-97. 2007
    ..Here, we apply hydrodynamic tail vein injection to deliver and express large genomic DNA inserts > 100 kb in vivo...
  36. ncbi request reprint Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes
    Alan L Parker
    British Heart Foundation Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, 126 University Place, University of Glasgow, G12 8TA, United Kingdom
    Blood 108:2554-61. 2006
    ..Our results indicate a common and pivotal role for distinct vitamin K-dependent coagulation factors in mediating hepatocyte transduction by adenoviruses in vitro and in vivo...
  37. doi request reprint Adenovirus serotype 5 hexon mediates liver gene transfer
    Simon N Waddington
    Department of Haematology, Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, London NW3 2PF, UK
    Cell 132:397-409. 2008
    ..Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo...
  38. pmc Targeting of adenovirus serotype 5 (Ad5) and 5/47 pseudotyped vectors in vivo: fundamental involvement of coagulation factors and redundancy of CAR binding by Ad5
    Simon N Waddington
    Department of Haematology, Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, London NW3 2PF, United Kingdom
    J Virol 81:9568-71. 2007
    ..Hence, coagulation factors play a pivotal role in selectively mediating liver hepatocyte transduction of Ad5 and Ad5/47 vectors...
  39. ncbi request reprint The influence of blood on in vivo adenovirus bio-distribution and transduction
    Andrew H Baker
    British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
    Mol Ther 15:1410-6. 2007
    ..Unraveling and characterizing these mechanisms will be of fundamental importance both for understanding basic Ad biology in vivo and for refinement and optimization of Ad vectors for human gene therapy...