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Regulated promoters

  • Chapter
Gene Therapy for Autoimmune and Inflammatory Diseases

Part of the book series: Milestones in Drug Therapy ((MDT))

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Abstract

Over the past decades gene therapy has emerged as a promising approach for treatment of a variety of diseases including monogenic diseases, cancer, neurodegenerative disorders, autoimmune and inflammatory diseases. However, efficacy and safety remain the major challenges for turning gene therapy into a clinical reality. Several advances in vectorology have provided opportunities to address these issues including transductional and transcriptional targeting of viral vectors. The prior involves the modification of the virus tropism in order to increase the efficiency and specificity of target cell transduction. The latter comprises the use of cis-regulatory elements, such as promoters and enhancers (Fig. 1), to restrict transgene expression to specific tissues or patho-physiological conditions. Here we focus on recent developments and applications of endogenously-regulated promoter systems in gene therapy for autoimmune and inflammatory diseases, in particular rheumatoid arthritis (RA).

Schematic overview of a typical TATA-dependent promoter, its cis-regulatory sequences and interactions between regulatory proteins and the transcription initiation complex. The lower part displays the core promoter region which is the essential sequence for transcription initiation. In eukaryotes, the most common type core promoter is the TATA box that is the binding site for the transcription factor TATA binding protein (TBP). After TBP binds the TATA box, a number of TBP-associated factors (TAFII) and RNA polymerase (Pol II) combine around the TATA box to form the preinitiation complex (PIC). The TAFII, TFIIH has helicase activity and is involved in opening the double helical DNA strands. The PIC only drives a low rate of transcription. The transcriptional rate is further enhanced or inhibited by regulatory factors along with any associated co-activators or co-repressors. The cis-regulatory elements that drive tissue- or context-specific expression are predominantly located in the proximal-promoter region, depicted in the left part of the diagram. Regulatory factors consist of protein complexes, often hetero- or homodimers, that bind on their cognate binding sites (TFBS). Transcription factors (TF) can transactivate or repress the activity of the PIC and work cooperatively by stabilizing each other when forming DNA-protein complexes. Co-activators mediate the influence of regulatory factors through protein-protein interaction between a TF and the PIC. Additional fine-tuning of transcription is accomplished via more distal DNA elements as enhancers, displayed on the right part. These sequences exert their activating effects independently from position or orientation and are obtained by accomplishing a specific DNA formation. Extensive methylation of CG-rich regions in promoter sequences (CpG Islands), e.g., viral promoters, compromises the binding of regulatory factors and leads to inactivation of the promoter. The Kozak sequence (GCCRCC) is frequently placed directly upstream of the translation start codon (ATG) for enhanced translation of transgenes in gene therapy approaches.

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References

  1. Chen P, Tian J, Kovesdi I, Bruder JT (2008) Promoters influence the kinetics of transgene expression following adenovector gene delivery. J Gene Med 10: 123–131

    Article  CAS  PubMed  Google Scholar 

  2. Brooks AR, Harkins RN, Wang P, Qian HS, Liu P, Rubanyi GM (2004) Transcriptional silencing is associated with extensive methylation of the CMV promoter following adenoviral gene delivery to muscle. J Gene Med 6: 395–404

    Article  CAS  PubMed  Google Scholar 

  3. Adriaansen J, Kuhlman RR, van HJ, Kaynor C, Vervoordeldonk MJ, Tak PP (2006) Intraarticular interferon-beta gene therapy ameliorates adjuvant arthritis in rats. Hum Gene Ther 17: 985–996

    Article  CAS  PubMed  Google Scholar 

  4. Adriaansen J, Fallaux FJ, de Cortie CJ, Vervoordeldonk MJ, Tak PP (2007) Local delivery of beta interferon using an adeno-associated virus type 5 effectively inhibits adjuvant arthritis in rats. J Gen Virol 88: 1717–1721

    Article  CAS  PubMed  Google Scholar 

  5. Geurts J, Arntz OJ, Bennink MB, Joosten LA, van den Berg WB, van de Loo FA (2007) Application of a disease-regulated promoter is a safer mode of local IL-4 gene therapy for arthritis. Gene Ther 14: 1632–1638

    Article  CAS  PubMed  Google Scholar 

  6. Pan RY, Xiao X, Chen SL, Li J, Lin LC, Wang HJ, Tsao YP (1999) Disease-inducible transgene expression from a recombinant adeno-associated virus vector in a rat arthritis model. J Virol 73: 3410–3417

    CAS  PubMed  Google Scholar 

  7. van de Loo FA, de Hooge AS, Smeets RL, Bakker AC, Bennink MB, Arntz OJ, Joosten LA, van Beuningen HM, van der Kraan PK, Varley AW et al. (2004) An inflammation-inducible adenoviral expression system for local treatment of the arthritic joint. Gene Ther 11: 581–590

    Article  PubMed  Google Scholar 

  8. Weber EL, Cannon PM (2007) Promoter choice for retroviral vectors: transcriptional strength versus trans-activation potential. Hum Gene Ther 18: 849–860

    Article  CAS  PubMed  Google Scholar 

  9. Zychlinski D, Schambach A, Modlich U, Maetzig T, Meyer J, Grassman E, Mishra A, Baum C (2008) Physiological promoters reduce the genotoxic risk of integrating gene vectors. Mol Ther 16: 718–725

    Article  CAS  PubMed  Google Scholar 

  10. Lubberts E, Joosten LA, Chabaud M, van den Bersselaar L, Oppers B, Coenen-de Roo CJ, Richards CD, Miossec P, van den Berg WB (2000) IL-4 gene therapy for collagen arthritis suppresses synovial IL-17 and osteoprotegerin ligand and prevents bone erosion. J Clin Invest 105: 1697–1710

    Article  CAS  PubMed  Google Scholar 

  11. Blaney Davidson EN, Vitters EL, van den Berg WB, van der Kraan PM (2006) TGF beta-induced cartilage repair is maintained but fibrosis is blocked in the presence of Smad7. Arthritis Res Ther 8, R65

    Article  PubMed  Google Scholar 

  12. Bakker AC, van de Loo FA, van Beuningen HM, Sime P, van Lent PL, van der Kraan PM, Richards CD, van den Berg WB (2001) Overexpression of active TGF-beta-1 in the murine knee joint: evidence for synovial-layer-dependent chondro-osteophyte formation. Osteoarthritis Cartilage 9: 128–136

    Article  CAS  PubMed  Google Scholar 

  13. Robson T, Hirst DG (2003) Transcriptional targeting in cancer gene therapy. J Biomed Biotechnol 110–137

    Google Scholar 

  14. Guo ZS, Li Q, Bartlett DL, Yang JY, Fang B (2008) Gene transfer: the challenge of regulated gene expression. Trends Mol Med 14: 410–418

    Article  CAS  PubMed  Google Scholar 

  15. Suffredini AF, Fantuzzi G, Badolato R, Oppenheim JJ, O’Grady NP (1999) New insights into the biology of the acute phase response. J Clin Immunol 19: 203–214

    Article  CAS  PubMed  Google Scholar 

  16. Burke B, Pridmore A, Harraghy N, Collick A, Brown J, Mitchell T (2004) Transgenic mice showing inflammation-inducible overexpression of granulocyte macrophage colony-stimulating factor. Clin Diagn Lab Immunol 11: 588–598

    CAS  PubMed  Google Scholar 

  17. Zhang N, Ahsan MH, Purchio AF, West DB (2005) Serum amyloid A-luciferase transgenic mice: response to sepsis, acute arthritis, and contact hypersensitivity and the effects of proteasome inhibition. J Immunol 174: 8125–8134

    CAS  PubMed  Google Scholar 

  18. van de Loo FA, Joosten LA, van Lent PL, Arntz OJ, van den Berg WB (1995) Role of interleukin-1, tumor necrosis factor alpha, and interleukin-6 in cartilage proteoglycan metabolism and destruction. Effect of in situ blocking in murine antigen-and zymosan-induced arthritis. Arthritis Rheum 38: 164–172

    Article  PubMed  Google Scholar 

  19. Klimiuk PA, Sierakowski S, Latosiewicz R, Cylwik JP, Cylwik B, Skowronski J, Chwiecko J (2003) Interleukin-6, soluble interleukin-2 receptor and soluble interleukin-6 receptor in the sera of patients with different histological patterns of rheumatoid synovitis. Clin Exp Rheumatol 21: 63–69

    CAS  PubMed  Google Scholar 

  20. Okamoto H, Yamamura M, Morita Y, Harada S, Makino H, Ota Z (1997) The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis. Arthritis Rheum 40: 1096–1105

    Article  CAS  PubMed  Google Scholar 

  21. Uson J, Balsa A, Pascual-Salcedo D, Cabezas JA, Gonzalez-Tarrio JM, Martin-Mola E, Fontan G (1997) Soluble interleukin 6 (IL-6) receptor and IL-6 levels in serum and synovial fluid of patients with different arthropathies. J Rheumatol 24: 2069–2075

    CAS  PubMed  Google Scholar 

  22. Madson KL, Moore TL, Lawrence JM III, Osborn TG (1994) Cytokine levels in serum and synovial fluid of patients with juvenile rheumatoid arthritis. J Rheumatol 21: 2359–2363

    CAS  PubMed  Google Scholar 

  23. Aikawa Y, Morimoto K, Yamamoto T, Chaki H, Hashiramoto A, Narita H, Hirono S, Shiozawa S (2008) Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1. Nat Biotechnol 26: 817–823

    Article  CAS  PubMed  Google Scholar 

  24. Firestein GS, Manning AM (1999) Signal transduction and transcription factors in rheumatic disease. Arthritis Rheum 42: 609–621

    Article  CAS  PubMed  Google Scholar 

  25. Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L, Manning AM, Firestein GS (2001) c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 108: 73–81

    CAS  PubMed  Google Scholar 

  26. Li Q, Verma IM (2002) NF-kappaB regulation in the immune system. Nat Rev Immunol 2: 725–734

    Article  CAS  PubMed  Google Scholar 

  27. Tak PP, Gerlag DM, Aupperle KR, van de Geest DA, Overbeek M, Bennett BL, Boyle DL, Manning AM, Firestein GS (2001) Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial inflammation. Arthritis Rheum 44: 1897–1907

    Article  CAS  PubMed  Google Scholar 

  28. Nishioka K, Ohshima S, Umeshita-Sasai M, Yamaguchi N, Mima T, Nomura S, Murata N, Shimizu M, Miyake T, Yoshizaki K et al. (2000) Enhanced expression and DNA binding activity of two CCAAT/enhancer-binding protein isoforms, C/EBPbeta and C/EBPdelta, in rheumatoid synovium. Arthritis Rheum 43: 1591–1596

    Article  CAS  PubMed  Google Scholar 

  29. Pope RM, Lovis R, Mungre S, Perlman H, Koch AE, Haines GK III (1999) C/EBP beta in rheumatoid arthritis: correlation with inflammation, not disease specificity. Clin Immunol 91: 271–282

    Article  CAS  PubMed  Google Scholar 

  30. Khoury M, Adriaansen J, Vervoordeldonk MJ, Gould D, Chernajovsky Y, Bigey P, Bloquel C, Scherman D, Tak PP, Jorgensen C et al. (2007) Inflammation-inducible anti-TNF gene expression mediated by intra-articular injection of serotype 5 adeno-associated virus reduces arthritis. J Gene Med 9: 596–604

    Article  CAS  PubMed  Google Scholar 

  31. Adriaansen J, Khoury M, de Cortie CJ, Fallaux FJ, Bigey P, Scherman D, Gould DJ, Chernajovsky Y, Apparailly F, Jorgensen C et al. (2007) Reduction of arthritis following intra-articular administration of an adeno-associated virus serotype 5 expressing a disease-inducible TNF-blocking agent. Ann Rheum Dis 66: 1143–1150

    Article  CAS  PubMed  Google Scholar 

  32. Clancy RM, Amin AR, Abramson SB (1998) The role of nitric oxide in inflammation and immunity. Arthritis Rheum 41: 1141–1151

    Article  CAS  PubMed  Google Scholar 

  33. Zhang N, Weber A, Li B, Lyons R, Contag PR, Purchio AF, West DB (2003) An inducible nitric oxide synthase-luciferase reporter system for in vivo testing of anti-inflammatory compounds in transgenic mice. J Immunol 170: 6307–6319

    CAS  PubMed  Google Scholar 

  34. Zhang N, Fang Z, Contag PR, Purchio AF, West DB (2004) Tracking angiogenesis induced by skin wounding and contact hypersensitivity using a Vegfr2-luciferase transgenic mouse. Blood 103: 617–626

    Article  CAS  PubMed  Google Scholar 

  35. Jackson JR, Seed MP, Kircher CH, Willoughby DA, Winkler JD (1997) The codependence of angiogenesis and chronic inflammation. FASEB J 11: 457–465

    CAS  PubMed  Google Scholar 

  36. Kanerva A, Bauerschmitz GJ, Yamamoto M, Lam JT, Alvarez RD, Siegal GP, Curiel DT, Hemminki A (2004) A cyclooxygenase-2 promoter-based conditionally replicating adenovirus with enhanced infectivity for treatment of ovarian adenocarcinoma. Gene Ther 11: 552–559

    Article  CAS  PubMed  Google Scholar 

  37. Rachakonda PS, Rai MF, Schmidt MF (2008) Application of inflammation-responsive promoter for an in vitro arthritis model. Arthritis Rheum 58: 2088–2097

    Article  CAS  PubMed  Google Scholar 

  38. Campbell SE, Bennett D, Nasir L, Gault EA, Argyle DJ (2005) Disease-and cell-type-specific transcriptional targeting of vectors for osteoarthritis gene therapy: further development of a clinical canine model. Rheumatology (Oxford) 44: 735–743

    Article  CAS  Google Scholar 

  39. Wang T, Stormo GD (2003) Combining phylogenetic data with co-regulated genes to identify regulatory motifs. Bioinformatics 19: 2369–2380

    Article  CAS  PubMed  Google Scholar 

  40. Wasserman WW, Sandelin A (2004) Applied bioinformatics for the identification of regulatory elements. Nat Rev Genet 5: 276–287

    Article  CAS  PubMed  Google Scholar 

  41. Zhang MQ (2007) Computational analyses of eukaryotic promoters. BMCBioinformatics 8 Suppl 6, S3

    Google Scholar 

  42. Zhao G, Schriefer LA, Stormo GD (2007) Identification of muscle-specific regulatory modules in Caenorhabditis elegans. Genome Res 17: 348–357

    Article  CAS  PubMed  Google Scholar 

  43. Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K, Ponjavic J, Semple CA, Taylor MS, Engstrom PG, Frith MC et al. (2006) Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38: 626–635

    Article  CAS  PubMed  Google Scholar 

  44. Ponjavic J, Lenhard B, Kai C, Kawai J, Carninci P, Hayashizaki Y, Sandelin A (2006) Transcriptional and structural impact of TATA-initiation site spacing in mammalian core promoters. Genome Biol 7, R78

    Article  PubMed  Google Scholar 

  45. Davies SR, Chang LW, Patra D, Xing X, Posey K, Hecht J, Stormo GD, Sandell LJ (2007) Computational identification and functional validation of regulatory motifs in cartilage-expressed genes. Genome Res 17: 1438–1447

    Article  CAS  PubMed  Google Scholar 

  46. D’Souza CA, Chopra V, Varhol R, Xie YY, Bohacec S, Zhao Y, Lee LL, Bilenky M, Portales-Casamar E, He A et al. (2008) Identification of a set of genes showing regionally enriched expression in the mouse brain. BMCNeurosci 9, 66

    Google Scholar 

  47. Portales-Casamar E, Kirov S, Lim J, Lithwick S, Swanson MI, Ticoll A, Snoddy J, Wasserman WW (2007) PAZAR: a framework for collection and dissemination of cis-regulatory sequence annotation. Genome Biol 8, R207

    Article  PubMed  Google Scholar 

  48. Yang GS, Banks KG, Bonaguro RJ, Wilson G, Dreolini L, de Leeuw CN, Liu L, Swanson DJ, Goldowitz D, Holt RA et al. (2009) Next generation tools for high-throughput promoter and expression analysis employing single-copy knock-ins at the Hprt1 locus. Genomics 93: 196–204

    Article  CAS  PubMed  Google Scholar 

  49. Li J, Liu ZJ, Pan YC, Liu Q, Fu X, Cooper NG, Li Y, Qiu M, Shi T (2007) Regulatory module network of basic/helix-loop-helix transcription factors in mouse brain. Genome Biol 8, R244

    Article  PubMed  Google Scholar 

  50. Varley AW, Geiszler SM, Gaynor RB, Munford RS (1997) A two-component expression system that responds to inflammatory stimuli in vivo. Nat Biotechnol 15: 1002–1006

    Article  CAS  PubMed  Google Scholar 

  51. Bakker AC, van de Loo FA, Joosten LA, Arntz OJ, Varley AW, Munford RS, van den Berg WB (2002) C3-Tat/HIV-regulated intraarticular human interleukin-1 receptor antagonist gene therapy results in efficient inhibition of collagen-induced arthritis superior to cytomegalovirus-regulated expression of the same transgene. Arthritis Rheum 46: 1661–1670

    Article  CAS  PubMed  Google Scholar 

  52. Miagkov AV, Varley AW, Munford RS, Makarov SS (2002) Endogenous regulation of a therapeutic transgene restores homeostasis in arthritic joints. J Clin Invest 109: 1223–1229

    CAS  PubMed  Google Scholar 

  53. Chen P, Mayne M, Power C, Nath A (1997) The Tat protein of HIV-1 induces tumor necrosis factoralpha production. Implications for HIV-1-associated neurological diseases. J Biol Chem 272: 22385–22388

    Article  CAS  PubMed  Google Scholar 

  54. Nath A, Conant K, Chen P, Scott C, Major EO (1999) Transient exposure to HIV-1 Tat protein results in cytokine production in macrophages and astrocytes. A hit and run phenomenon. J Biol Chem 274: 17098–17102

    Article  CAS  PubMed  Google Scholar 

  55. Park IW, Wang JF, Groopman JE (2001) HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes. Blood 97: 352–358

    Article  CAS  PubMed  Google Scholar 

  56. Toniatti C, Bujard H, Cortese R, Ciliberto G (2004) Gene therapy progress and prospects: transcription regulatory systems. Gene Ther 11: 649–657

    Article  CAS  PubMed  Google Scholar 

  57. le Guiner C, Stieger K, Snyder RO, Rolling F, Moullier P (2007) Immune responses to gene product of inducible promoters. Curr Gene Ther 7: 334–346

    Article  PubMed  Google Scholar 

  58. Stieger K, Belbellaa B, le Guiner C, Moullier P, Rolling F (2009) In vivo gene regulation using tetracycline-regulatable systems. Adv Drug Deliv Rev 61: 527–541

    Article  CAS  PubMed  Google Scholar 

  59. Courties G, Presumey J, Duroux-Richard I, Jorgensen C, Apparailly F (2009) RNA interferencebased gene therapy for successful treatment of rheumatoid arthritis. Expert Opin Biol Ther 9: 535–538

    Article  CAS  PubMed  Google Scholar 

  60. Khoury M, Escriou V, Courties G, Galy A, Yao R, Largeau C, Scherman D, Jorgensen C, Apparailly F (2008) Efficient suppression of murine arthritis by combined anticytokine small interfering RNA lipoplexes. Arthritis Rheum 58: 2356–2367

    Article  CAS  PubMed  Google Scholar 

  61. Wiznerowicz M, Szulc J, Trono D (2006) Tuning silence: conditional systems for RNA interference. Nat Methods 3: 682–688

    Article  CAS  PubMed  Google Scholar 

  62. Stegmeier F, Hu G, Rickles RJ, Hannon GJ, Elledge SJ (2005) A lentiviral microRNA-based system for single-copy polymerase II-regulated RNA interference in mammalian cells. Proc Natl Acad Sci USA 102: 13212–13217

    Article  CAS  PubMed  Google Scholar 

  63. Yang W, Paschen W (2008) Conditional gene silencing in mammalian cells mediated by a stressinducible promoter. Biochem Biophys Res Commun 365: 521–527

    Article  CAS  PubMed  Google Scholar 

  64. van Eden W, van der Zee R, Prakken B (2005) Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat Rev Immunol 5: 318–330

    Article  PubMed  Google Scholar 

  65. Yoshizaki K, Wakita H, Takeda K, Takahashi K (2008) Conditional expression of microRNA against E-selectin inhibits leukocyte-endothelial adhesive interaction under inflammatory condition. Biochem Biophys Res Commun 371: 747–751

    Article  CAS  PubMed  Google Scholar 

  66. Evans CH, Ghivizzani SC, Robbins PD (2009) Orthopedic gene therapy in 2008. Mol Ther 17: 231–244

    Article  CAS  PubMed  Google Scholar 

  67. Evans CH, Robbins PD, Ghivizzani SC, Wasko MC, Tomaino MM, Kang R, Muzzonigro TA, Vogt M, Elder EM, Whiteside TL et al. (2005) Gene transfer to human joints: progress toward a gene therapy of arthritis. Proc Natl Acad Sci USA 102: 8698–8703

    Article  CAS  PubMed  Google Scholar 

  68. Wehling P, Reinecke J, Baltzer AA, Granrath M, Schulitz KP, Schultz C, Krauspe R, Whiteside T, Elder E, Ghivizzani SC et al. (2009) Clinical responses to gene therapy in joints of two subjects with rheumatoid arthritis. Hum Gene Ther 20: 97–101

    Article  CAS  PubMed  Google Scholar 

  69. Chan JM, Villarreal G, Jin WW, Stepan T, Burstein H, Wahl SM (2002) Intraarticular gene transfer of TNFR:Fc suppresses experimental arthritis with reduced systemic distribution of the gene product. Mol Ther 6: 727–736

    Article  CAS  PubMed  Google Scholar 

  70. Atzeni F, Bendtzen K, Bobbio-Pallavicini F, Conti F, Cutolo M, Montecucco C, Sulli A, Valesini G, Sarzi-Puttini P (2008) Infections and treatment of patients with rheumatic diseases. Clin Exp Rheumatol 26, S67–S73

    CAS  PubMed  Google Scholar 

  71. Favalli EG, Desiati F, Atzeni F, Sarzi-Puttini P, Caporali R, Pallavicini FB, Gorla R, Filippini M, Marchesoni A (2009) Serious infections during anti-TNFalpha treatment in rheumatoid arthritis patients. Autoimmun Rev 8: 266–273

    Article  CAS  PubMed  Google Scholar 

  72. Brown BD, Venneri MA, Zingale A, Sergi SL, Naldini L (2006) Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer. Nat Med 12: 585–591

    Article  CAS  PubMed  Google Scholar 

  73. Brown BD, Gentner B, Cantore A, Colleoni S, Amendola M, Zingale A, Baccarini A, Lazzari G, Galli C, Naldini L (2007) Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state. Nat Biotechnol 25: 1457–1467

    Article  CAS  PubMed  Google Scholar 

  74. Varley AW, Coulthard MG, Meidell RS, Gerard RD, Munford RS (1995) Inflammation-induced recombinant protein expression in vivo using promoters from acute-phase protein genes. Proc Natl Acad Sci USA 92: 5346–5350

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, 6525 GA, The Netherlands

    Jeroen Geurts, Wim B. van den Berg & Fons A. J. van de Loo

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  1. Jeroen Geurts
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  2. Wim B. van den Berg
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  3. Fons A. J. van de Loo
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Editors and Affiliations

  1. Bone and Joint Research Unit Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

    Yuti Chernajovsky

  2. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Paul D. Robbins

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Geurts, J., van den Berg, W.B., van de Loo, F.A.J. (2010). Regulated promoters. In: Chernajovsky, Y., Robbins, P.D. (eds) Gene Therapy for Autoimmune and Inflammatory Diseases. Milestones in Drug Therapy. Springer, Basel. https://doi.org/10.1007/978-3-0346-0165-8_10

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