• 1
    Moolten FL, Cupples LA. A model for predicting the risk of cancer consequent to retroviral gene therapy. Hum. Gene Ther. 1992; 3: 479–88.
  • 2
    Chen SY, Shiau AL, Li YT et al. Suppression of collagen-induced arthritis by intra-articular lentiviral vector-mediated delivery of Toll-like receptor 7 short hairpin RNA gene. Gene Ther. 2012; 19: 752–60.
  • 3
    Roybal JL, Endo M, Radu A et al. Early gestational gene transfer of IL-10 by systemic administration of lentiviral vector can prevent arthritis in a murine model. Gene Ther. 2011; 18: 719–26.
  • 4
    Iyer S, Bergquist K, Young K et al. Mitochondrial Gene Therapy Improves Respiration, Biogenesis, and Transcription in G11778A Leber's Hereditary Optic Neuropathy and T8993G Leigh's Syndrome Cells. Hum. Gene Ther. 2012; 23: 647–57.
  • 5
    Iyer S, Xiao E, Alsayegh K et al. Mitochondrial gene replacement in human pluripotent stem cell-derived neural progenitors. Gene Ther. 2012; 19: 469–75.
  • 6
    Matsuda R, Kezuka T, Nishiyama C et al. Suppression of Murine Experimental Autoimmune Optic Neuritis by Mature Dendritic Cells Transfected with Calcitonin Gene-Related Peptide Gene. Invest. Ophthalmol. Vis. Sci. 2012; 53: 54755485.
  • 7
    Broadstock M, Yanez-Munoz RJ. Challenges for gene therapy of CNS disorders and implications for Parkinson's disease therapies. Hum. Gene Ther. 2012; 23: 340–3.
  • 8
    Mittermeyer G, Christine CW, Rosenbluth KH et al. Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson's disease. Hum. Gene Ther. 2012; 23: 377–81.
  • 9
    Goins WF, Goss JR, Chancellor MB et al. Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain. Gene Ther. 2009; 16: 558–69.
  • 10
    Steers WD, Kolbeck S, Creedon D et al. Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J. Clin. Invest. 1991; 88: 1709–15.
  • 11
    Levi-Montalcini R. The nerve growth factor 35 years later. Science 1987; 237: 1154–62.
  • 12
    Hellweg R, Raivich G, Hartung HD et al. Axonal transport of endogenous nerve growth factor (NGF) and NGF receptor in experimental diabetic neuropathy. Exp. Neurol. 1994; 130: 24–30.
  • 13
    Apfel SC, Arezzo JC, Brownlee M et al. Nerve growth factor administration protects against experimental diabetic sensory neuropathy. Brain Res. 1994; 634: 7–12.
  • 14
    Unger JW, Klitzsch T, Pera S et al. Nerve growth factor (NGF) and diabetic neuropathy in the rat: morphological investigations of the sural nerve, dorsal root ganglion, and spinal cord. Exp. Neurol. 1998; 153: 23–34.
  • 15
    Sasaki K, Chancellor MB, Goins WF et al. Gene therapy using replication-defective herpes simplex virus vectors expressing nerve growth factor in a rat model of diabetic cystopathy. Diabetes 2004; 53: 2723–30.
  • 16
    Liu HT, Kuo HC. Urinary nerve growth factor levels are increased in patients with bladder outlet obstruction with overactive bladder symptoms and reduced after successful medical treatment. Urology 2008; 72: 104–8.
  • 17
    Zvara P, Kliment J Jr, DeRoss AL et al. Differential expression of bladder neurotrophic factor mRNA in male and female rats after bladder outflow obstruction. J. Urol. 2002; 168: 2682–8.
  • 18
    Kim JC, Kim DB, Seo SI et al. Nerve growth factor and vanilloid receptor expression, and detrusor instability, after relieving bladder outlet obstruction in rats. BJU Int. 2004; 94: 915–8.
  • 19
    Lowe EM, Anand P, Terenghi G et al. Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis. Br. J. Urol. 1997; 79: 572–7.
  • 20
    Pinto R, Lopes T, Frias B et al. Trigonal injection of botulinum toxin A in patients with refractory bladder pain syndrome/interstitial cystitis. Eur. Urol. 2010; 58: 360–5.
  • 21
    Chuang YC, Fraser MO, Yu Y et al. The role of bladder afferent pathways in bladder hyperactivity induced by the intravesical administration of nerve growth factor. J. Urol. 2001; 165: 975–9.
  • 22
    Yoshimura N, Bennett NE, Hayashi Y et al. Bladder overactivity and hyperexcitability of bladder afferent neurons after intrathecal delivery of nerve growth factor in rats. J. Neurosci. 2006; 26: 10847–55.
  • 23
    Lamb K, Gebhart GF, Bielefeldt K. Increased nerve growth factor expression triggers bladder overactivity. J. Pain 2004; 5: 150–6.
  • 24
    Tyagi P, Banerjee R, Basu S et al. Intravesical antisense therapy for cystitis using TAT-peptide nucleic acid conjugates. Mol. Pharm. 2006; 3: 398–406.
  • 25
    Boros P, Miller CM. Hepatocyte growth factor: a multifunctional cytokine. Lancet 1995; 345: 293–5.
  • 26
    Taniyama Y, Morishita R, Aoki M et al. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease. Gene Ther. 2001; 8: 181–9.
  • 27
    Taniyama Y, Morishita R, Nakagami H et al. Potential contribution of a novel antifibrotic factor, hepatocyte growth factor, to prevention of myocardial fibrosis by angiotensin II blockade in cardiomyopathic hamsters. Circulation 2000; 102: 246–52.
  • 28
    Katsuno T, Ozaki T, Saka Y et al. Low serum cultured adipose tissue-derived stromal cells ameliorate acute kidney injury in rats. Cell Transplant. 2012 Sep 7. [Epub ahead of print] PubMed PMID: 22963874.
  • 29
    Ku JH, Kim Y, Moon KC et al. In vivo hepatocyte growth factor gene transfer to bladder smooth muscle after bladder outlet obstruction in the rat: a morphometric analysis. J. Urol. 2006; 176: 1230–5.
  • 30
    Shapiro S. Neurotransmission by neurons that use serotonin, noradrenaline, glutamate, glycine, and gamma-aminobutyric acid in the normal and injured spinal cord. Neurosurgery 1997; 40: 168–76.
  • 31
    Liu J, Wolfe D, Hao S et al. Peripherally delivered glutamic acid decarboxylase gene therapy for spinal cord injury pain. Mol. Ther. 2004; 10: 57–66.
  • 32
    Hao S, Mata M, Wolfe D et al. Gene transfer of glutamic acid decarboxylase reduces neuropathic pain. Ann. Neurol. 2005; 57: 914–8.
  • 33
    Igawa Y, Mattiasson A, Andersson KE. Effects of GABA-receptor stimulation and blockade on micturition in normal rats and rats with bladder outflow obstruction. J. Urol. 1993; 150: 537–42.
  • 34
    Miyazato M, Sasatomi K, Hiragata S et al. GABA receptor activation in the lumbosacral spinal cord decreases detrusor overactivity in spinal cord injured rats. J. Urol. 2008; 179: 1178–83.
  • 35
    Miyazato M, Sugaya K, Goins WF et al. Herpes simplex virus vector-mediated gene delivery of glutamic acid decarboxylase reduces detrusor overactivity in spinal cord-injured rats. Gene Ther. 2009; 16: 660–8.
  • 36
    Miyazato M, Sugaya K, Saito S et al. Suppression of detrusor-sphincter dyssynergia by herpes simplex virus vector mediated gene delivery of glutamic acid decarboxylase in spinal cord injured rats. J. Urol. 2010; 184: 1204–10.
  • 37
    Ratner V. Interstitial cystitis: a chronic inflammatory bladder condition. World J. Urol. 2001; 19: 157–9.
  • 38
    Glazer EJ, Basbaum AI. Leucine enkephalin: localization in and axoplasmic transport by sacral parasympathetic preganglionic neurons. Science 1980; 208: 1479–81.
  • 39
    Dray A, Nunan L, Wire W. Central delta-opioid receptor interactions and the inhibition of reflex urinary bladder contractions in the rat. Br. J. Pharmacol. 1985; 85: 717–26.
  • 40
    Yokoyama H, Sasaki K, Franks ME et al. Gene therapy for bladder overactivity and nociception with herpes simplex virus vectors expressing preproenkephalin. Hum. Gene Ther. 2009; 20: 63–71.
  • 41
    Yoshimura N, Franks ME, Sasaki K et al. Gene therapy of bladder pain with herpes simplex virus (HSV) vectors expressing preproenkephalin (PPE). Urology 2001; 57: 116.
  • 42
    Chuang YC, Chou AK, Wu PC et al. Gene therapy for bladder pain with gene gun particle encoding pro-opiomelanocortin cDNA. J. Urol. 2003; 170: 2044–8.
  • 43
    Lu CY, Chou AK, Wu CL et al. Gene-gun particle with pro-opiomelanocortin cDNA produces analgesia against formalin-induced pain in rats. Gene Ther. 2002; 9: 1008–14.
  • 44
    Mousa SA, Zhang Q, Sitte N et al. β-Endorphin-containing memory-cells and mu-opioid receptors undergo transport to peripheral inflamed tissue. J. Neuroimmunol. 2001; 115: 7178.
  • 45
    Keay S. Cell signaling in interstitial cystitis/painful bladder syndrome. Cell. Signal. 2008; 20: 2174–9.
  • 46
    Erickson DR, Xie SX, Bhavanandan VP et al. A comparison of multiple urine markers for interstitial cystitis. J. Urol. 2002; 167: 2461–9.
  • 47
    Ogawa T, Homma T, Igawa Y et al. CXCR3 binding chemokine and TNFSF14 over expression in bladder urothelium of patients with ulcerative interstitial cystitis. J. Urol. 2010; 183: 1206–12.
  • 48
    Peters KM, Diokno AC, Steinert BW. Preliminary study on urinary cytokine levels in interstitial cystitis: does intravesical bacille Calmette-Guerin treat interstitial cystitis by altering the immune profile in the bladder? Urology 1999; 54: 450–3.
  • 49
    Keystone EC, Ware CF. Tumor necrosis factor and anti-tumor necrosis factor therapies. J. Rheumatol. Suppl. 2010; 85: 27–39.
  • 50
    Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat. Rev. Neurosci. 2005; 6: 521–32.
  • 51
    Schafers M, Svensson CI, Sommer C et al. Tumor necrosis factor-alpha induces mechanical allodynia after spinal nerve ligation by activation of p38 MAPK in primary sensory neurons. J. Neurosci. 2003; 23: 2517–21.
  • 52
    Sommer C, Lindenlaub T, Teuteberg P et al. Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy. Brain Res. 2001; 913: 86–9.
  • 53
    Sommer C, Schmidt C, George A. Hyperalgesia in experimental neuropathy is dependent on the TNF receptor 1. Exp. Neurol. 1998; 151: 138–42.
  • 54
    Svensson CI, Schafers M, Jones TL et al. Spinal blockade of TNF blocks spinal nerve ligation-induced increases in spinal P-p38. Neurosci. Lett. 2005; 379: 209–13.
  • 55
    Funahashi Y, Oguchi T, Goins WF et al. Herpes simplex virus vector-mediated gene therapy of tumor necrosis factor-α blockade for bladder overactivity and nociception in rats. J. Urol. 2012, (in press).
  • 56
    te Velde AA, Huijbens RJ, Heije K et al. Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood 1990; 76: 1392–7.
  • 57
    Gautam S, Tebo JM, Hamilton TA. IL-4 suppresses cytokine gene expression induced by IFN-gamma and/or IL-2 in murine peritoneal macrophages. J. Immunol. 1992; 148: 1725–30.
  • 58
    Ueda T, Tamaki M, Ogawa O et al. Improvement of interstitial cystitis symptoms and problems that developed during treatment with oral IPD-1151T. J. Urol. 2000; 164: 1917–20.
  • 59
    Hao S, Mata M, Glorioso JC et al. HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain. Mol. Pain 2006; 2: 6. doi:10.1186/1744-8069-2-6
  • 60
    Oguchi T, Funahashi Y, Yokoyama H et al. Effect of herpes simplex virus vector-mediated interleukin-4 gene therapy on bladder overactivity and nociception. Gene Ther. 2012 Mar 8. doi:10.1038/gt.2012.24. [Epub ahead of print] PubMed PMID: 22402319.
  • 61
    Epperly MW, Bray JA, Esocobar P et al. Overexpression of the human manganese superoxide dismutase (MnSOD) transgene in subclones of murine hematopoietic progenitor cell line 32D cl 3 decreases irradiation-induced apoptosis but does not alter G2/M or G1/S phase cell cycle arrest. Radiat. Oncol. Investig. 1999; 7: 331–42.
  • 62
    Epperly MW, Gretton JA, DeFilippi SJ et al. Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmid/liposome (SOD2-PL) gene therapy. Radiat. Res. 2001; 155: 2–14.
  • 63
    Epperly MW, Defilippi S, Sikora C et al. Radioprotection of lung and esophagus by overexpression of the human manganese superoxide dismutase transgene. Mil. Med. 2002; 167: 71–3.
  • 64
    Fridovich I. Superoxide radical and superoxide dismutases. Annu. Rev. Biochem. 1995; 64: 97–112.
  • 65
    Kanai AJ, Zeidel ML, Lavelle JP et al. Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis. Am. J. Physiol. Renal Physiol. 2002; 283: F1304–12.
  • 66
    Andersson KE. Advances in the pharmacological control of the bladder. Exp. Physiol. 1999; 84: 195–213.
  • 67
    Chai TC, Gemalmaz H, Andersson KE et al. Persistently increased voiding frequency despite relief of bladder outlet obstruction. J. Urol. 1999; 161: 1689–93.
  • 68
    Fry CH, Wu C, Mundy AR. Bladder instability and detrusor smooth muscle function. Exp. Physiol. 1999; 84: 161–9.
  • 69
    Wojdan A, Freeden C, Woods M et al. Comparison of the potassium channel openers, WAY-133537, ZD6169, and celikalim on isolated bladder tissue and In vivo bladder instability in rat. J. Pharmacol. Exp. Ther. 1999; 289: 1410–8.
  • 70
    Andersson KE. The overactive bladder: pharmacologic basis of drug treatment. Urology 1997; 50: 74–84.
  • 71
    Imaizumi Y, Torii Y, Ohi Y et al. Ca2+ images and K+ current during depolarization in smooth muscle cells of the guinea-pig vas deferens and urinary bladder. J. Physiol. 1998; 510 (Pt 3): 705–19.
  • 72
    Christ GJ, Day NS, Day M et al. Bladder injection of “naked” hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2001; 281: R1699–709.
  • 73
    Ishida Y, Paul RJ. Ca2+ clearance in smooth muscle: lessons from gene-altered mice. J. Smooth Muscle Res. 2005; 41: 235–45.
  • 74
    Kim DK, Yoshimura N, Tyagi P, Chancellor MB. Role of Sarco/Endoplasmic Reticulum Calcium ATPase in Lower Urinary Tract Smooth Muscles. LUTS 2009; 1: s50–2.
  • 75
    Fraser MO, Lavelle JP, Sacks MS et al. The future of bladder control-intravesical drug delivery, a pinch of pepper, and gene therapy. Rev. Urol. 2002; 4: 1–11.
  • 76
    Engler H, Anderson SC, Machemer TR et al. Ethanol improves adenovirus-mediated gene transfer and expression to the bladder epithelium of rodents. Urology 1999; 53: 1049–53.
  • 77
    Gye MC, Oh YS, Lee JE, Shim S, Choi KJ, Ahn HS. Expression of coxsackievirus and adenovirus receptor isoforms in developing mouse bladder uroepithelium. Urology 2011; 77: 1009.e9–18.
  • 78
    Gur S, Kadowitz PJ, Hellstrom WJ. A review of current progress in gene and stem cell therapy for erectile dysfunction. Expert Opin. Biol. Ther. 2008; 8: 1521–38.
  • 79
    Samaniego LA, Webb AL, DeLuca NA. Functional interactions between herpes simplex virus immediate-early proteins during infection: gene expression as a consequence of ICP27 and different domains of ICP4. J. Virol. 1995; 69: 5705–15.
  • 80
    Samaniego LA, Wu N, DeLuca NA. The herpes simplex virus immediate-early protein ICP0 affects transcription from the viral genome and infected-cell survival in the absence of ICP4 and ICP27. J. Virol. 1997; 71: 4614–25.
  • 81
    Marconi P, Krisky D, Oligino T et al. Replication-defective herpes simplex virus vectors for gene transfer in vivo. Proc. Natl. Acad. Sci. U.S.A. 1996; 93: 11319–20.
  • 82
    Krisky DM, Marconi PC, Oligino T et al. Rapid method for construction of recombinant HSV gene transfer vectors. Gene Ther. 1997; 4: 1120–5.
  • 83
    Jiang C, Wechuck JB, Goins WF et al. Immobilized cobalt affinity chromatography provides a novel, efficient method for herpes simplex virus type 1 gene vector purification. J. Virol. 2004; 78: 8994–9006.
  • 84
    Ozuer A, Wechuck JB, Goins WF et al. Effect of genetic background and culture conditions on the production of herpesvirus-based gene therapy vectors. Biotechnol. Bioeng. 2002; 77: 685–92.
  • 85
    Ozuer A, Wechuck JB, Russell B et al. Evaluation of infection parameters in the production of replication-defective HSV-1 viral vectors. Biotechnol. Prog. 2002; 18: 476–82.
  • 86
    Srinivas RV, Balachandran N, Alonso-Caplen FV et al. Expression of herpes simplex virus glycoproteins in polarized epithelial cells. J. Virol. 1986; 58: 689–93.
  • 87
    Yokoyama T, Huard J, Chancellor MB. Myoblast therapy for stress urinary incontinence and bladder dysfunction. World J. Urol. 2000; 18: 56–61.
  • 88
    Chancellor MB, Yokoyama T, Tirney S et al. Preliminary results of myoblast injection into the urethra and bladder wall: a possible method for the treatment of stress urinary incontinence and impaired detrusor contractility. Neurourol. Urodyn. 2000; 19: 279–87.
  • 89
    Huard J, Yokoyama T, Pruchnic R et al. Muscle-derived cell-mediated ex vivo gene therapy for urological dysfunction. Gene Ther. 2002; 9: 1617–26.
  • 90
    Lu SH, Cannon TW, Chermanski C et al. Muscle-derived stem cells seeded into acellular scaffolds develop calcium-dependent contractile activity that is modulated by nicotinic receptors. Urology 2003; 61: 1285–91.
  • 91
    Wolfe D, Mata M, Fink DJ. A human trial of HSV-mediated gene transfer for the treatment of chronic pain. Gene Ther. 2009; 16: 455–60.
  • 92
    Wolfe D, Wechuck J, Krisky D et al. A clinical trial of gene therapy for chronic pain. Pain Med. 2009; 10: 1325–30.
  • 93
    Fink DJ, Wechuck J, Mata M et al. Gene therapy for pain: results of a phase I clinical trial. Ann. Neurol. 2011; 70: 207–12.