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. 2004 Oct;80(948):560–570. doi: 10.1136/pgmj.2003.017764

Gene therapy in clinical medicine

S Selkirk 1
PMCID: PMC1743106  PMID: 15466989

Abstract

Although the field of gene therapy has experienced significant setbacks and limited success, it is one of the most promising and active research fields in medicine. Interest in this therapeutic modality is based on the potential for treatment and cure of some of the most malignant and devastating diseases affecting humans. Over the next decade, the relevance of gene therapy to medical practices will increase and it will become important for physicians to understand the basic principles and strategies that underlie the therapeutic intervention. This report reviews the history, basic strategies, tools, and several current clinical paradigms for application.

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Selected References

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  1. Aartsma-Rus Annemieke, Janson Anneke A. M., Kaman Wendy E., Bremmer-Bout Mattie, den Dunnen Johan T., Baas Frank, van Ommen Gert-Jan B., van Deutekom Judith C. T. Therapeutic antisense-induced exon skipping in cultured muscle cells from six different DMD patients. Hum Mol Genet. 2003 Apr 15;12(8):907–914. doi: 10.1093/hmg/ddg100. [DOI] [PubMed] [Google Scholar]
  2. Abbas-Terki Toufik, Blanco-Bose William, Déglon Nicole, Pralong William, Aebischer Patrick. Lentiviral-mediated RNA interference. Hum Gene Ther. 2002 Dec 10;13(18):2197–2201. doi: 10.1089/104303402320987888. [DOI] [PubMed] [Google Scholar]
  3. Aitken M. L., Moss R. B., Waltz D. A., Dovey M. E., Tonelli M. R., McNamara S. C., Gibson R. L., Ramsey B. W., Carter B. J., Reynolds T. C. A phase I study of aerosolized administration of tgAAVCF to cystic fibrosis subjects with mild lung disease. Hum Gene Ther. 2001 Oct 10;12(15):1907–1916. doi: 10.1089/104303401753153956. [DOI] [PubMed] [Google Scholar]
  4. Amado R. G., Chen I. S. Lentiviral vectors--the promise of gene therapy within reach? Science. 1999 Jul 30;285(5428):674–676. doi: 10.1126/science.285.5428.674. [DOI] [PubMed] [Google Scholar]
  5. Anderson W. F., Fletcher J. C. Sounding boards. Gene therapy in human beings: when is it ethical to begin? N Engl J Med. 1980 Nov 27;303(22):1293–1297. doi: 10.1056/NEJM198011273032210. [DOI] [PubMed] [Google Scholar]
  6. Anderson W. F. Gene therapy. The best of times, the worst of times. Science. 2000 Apr 28;288(5466):627–629. doi: 10.1126/science.288.5466.627. [DOI] [PubMed] [Google Scholar]
  7. Anderson W. F. Human gene therapy. Science. 1992 May 8;256(5058):808–813. doi: 10.1126/science.1589762. [DOI] [PubMed] [Google Scholar]
  8. Anderson W. F. Prospects for human gene therapy. Science. 1984 Oct 26;226(4673):401–409. doi: 10.1126/science.6093246. [DOI] [PubMed] [Google Scholar]
  9. Andreoletti M., Loux N., Vons C., Nguyen T. H., Lorand I., Mahieu D., Simon L., Di Rico V., Vingert B., Chapman J. Engraftment of autologous retrovirally transduced hepatocytes after intraportal transplantation into nonhuman primates: implication for ex vivo gene therapy. Hum Gene Ther. 2001 Jan 20;12(2):169–179. doi: 10.1089/104303401750061230. [DOI] [PubMed] [Google Scholar]
  10. Banai S., Jaklitsch M. T., Shou M., Lazarous D. F., Scheinowitz M., Biro S., Epstein S. E., Unger E. F. Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation. 1994 May;89(5):2183–2189. doi: 10.1161/01.cir.89.5.2183. [DOI] [PubMed] [Google Scholar]
  11. Bass B. L. RNA interference. The short answer. Nature. 2001 May 24;411(6836):428–429. doi: 10.1038/35078175. [DOI] [PubMed] [Google Scholar]
  12. Björklund A., Stenevi U. Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res. 1979 Nov 30;177(3):555–560. doi: 10.1016/0006-8993(79)90472-4. [DOI] [PubMed] [Google Scholar]
  13. Blesch A., Conner J. M., Tuszynski M. H. Modulation of neuronal survival and axonal growth in vivo by tetracycline-regulated neurotrophin expression. Gene Ther. 2001 Jun;8(12):954–960. doi: 10.1038/sj.gt.3301480. [DOI] [PubMed] [Google Scholar]
  14. Brody S. L., Crystal R. G. Adenovirus-mediated in vivo gene transfer. Ann N Y Acad Sci. 1994 May 31;716:90–103. doi: 10.1111/j.1749-6632.1994.tb21705.x. [DOI] [PubMed] [Google Scholar]
  15. Bukrinsky M. I., Haggerty S., Dempsey M. P., Sharova N., Adzhubel A., Spitz L., Lewis P., Goldfarb D., Emerman M., Stevenson M. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature. 1993 Oct 14;365(6447):666–669. doi: 10.1038/365666a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Buller Richard E., Runnebaum Ingo B., Karlan Beth Y., Horowitz Jo Ann, Shahin Mark, Buekers Thomas, Petrauskas Stan, Kreienberg Rolf, Slamon Dennis, Pegram Mark. A phase I/II trial of rAd/p53 (SCH 58500) gene replacement in recurrent ovarian cancer. Cancer Gene Ther. 2002 Jul;9(7):553–566. doi: 10.1038/sj.cgt.7700472. [DOI] [PubMed] [Google Scholar]
  17. Burton E. A., Wechuck J. B., Wendell S. K., Goins W. F., Fink D. J., Glorioso J. C. Multiple applications for replication-defective herpes simplex virus vectors. Stem Cells. 2001;19(5):358–377. doi: 10.1634/stemcells.19-5-358. [DOI] [PubMed] [Google Scholar]
  18. Byrnes A. P., Rusby J. E., Wood M. J., Charlton H. M. Adenovirus gene transfer causes inflammation in the brain. Neuroscience. 1995 Jun;66(4):1015–1024. doi: 10.1016/0306-4522(95)00068-t. [DOI] [PubMed] [Google Scholar]
  19. Case S. S., Price M. A., Jordan C. T., Yu X. J., Wang L., Bauer G., Haas D. L., Xu D., Stripecke R., Naldini L. Stable transduction of quiescent CD34(+)CD38(-) human hematopoietic cells by HIV-1-based lentiviral vectors. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2988–2993. doi: 10.1073/pnas.96.6.2988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Chadwick S. L., Kingston H. D., Stern M., Cook R. M., O'Connor B. J., Lukasson M., Balfour R. P., Rosenberg M., Cheng S. H., Smith A. E. Safety of a single aerosol administration of escalating doses of the cationic lipid GL-67/DOPE/DMPE-PEG5000 formulation to the lungs of normal volunteers. Gene Ther. 1997 Sep;4(9):937–942. doi: 10.1038/sj.gt.3300481. [DOI] [PubMed] [Google Scholar]
  21. Chattopadhyay Munmun, Wolfe Darren, Huang Shaohua, Goss James, Glorioso Joseph C., Mata Marina, Fink David J. In vivo gene therapy for pyridoxine-induced neuropathy by herpes simplex virus-mediated gene transfer of neurotrophin-3. Ann Neurol. 2002 Jan;51(1):19–27. doi: 10.1002/ana.10061. [DOI] [PubMed] [Google Scholar]
  22. Chen K. S., Gage F. H. Somatic gene transfer of NGF to the aged brain: behavioral and morphological amelioration. J Neurosci. 1995 Apr;15(4):2819–2825. doi: 10.1523/JNEUROSCI.15-04-02819.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Chiocca E. A., Choi B. B., Cai W. Z., DeLuca N. A., Schaffer P. A., DiFiglia M., Breakefield X. O., Martuza R. L. Transfer and expression of the lacZ gene in rat brain neurons mediated by herpes simplex virus mutants. New Biol. 1990 Aug;2(8):739–746. [PubMed] [Google Scholar]
  24. Collins F. S. Cystic fibrosis: molecular biology and therapeutic implications. Science. 1992 May 8;256(5058):774–779. doi: 10.1126/science.1375392. [DOI] [PubMed] [Google Scholar]
  25. Crystal R. G., McElvaney N. G., Rosenfeld M. A., Chu C. S., Mastrangeli A., Hay J. G., Brody S. L., Jaffe H. A., Eissa N. T., Danel C. Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nat Genet. 1994 Sep;8(1):42–51. doi: 10.1038/ng0994-42. [DOI] [PubMed] [Google Scholar]
  26. Douglas J., Kelly P., Evans J. T., Garcia J. V. Efficient transduction of human lymphocytes and CD34+ cells via human immunodeficiency virus-based gene transfer vectors. Hum Gene Ther. 1999 Apr 10;10(6):935–945. doi: 10.1089/10430349950018337. [DOI] [PubMed] [Google Scholar]
  27. Dowell Joshua D., Rubart Michael, Pasumarthi Kishore B. S., Soonpaa Mark H., Field Loren J. Myocyte and myogenic stem cell transplantation in the heart. Cardiovasc Res. 2003 May 1;58(2):336–350. doi: 10.1016/s0008-6363(03)00254-2. [DOI] [PubMed] [Google Scholar]
  28. Dunckley M. G., Manoharan M., Villiet P., Eperon I. C., Dickson G. Modification of splicing in the dystrophin gene in cultured Mdx muscle cells by antisense oligoribonucleotides. Hum Mol Genet. 1998 Jul;7(7):1083–1090. doi: 10.1093/hmg/7.7.1083. [DOI] [PubMed] [Google Scholar]
  29. Eagle K. A., Guyton R. A., Davidoff R., Ewy G. A., Fonger J., Gardner T. J., Gott J. P., Herrmann H. C., Marlow R. A., Nugent W. C. ACC/AHA Guidelines for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery). American College of Cardiology/American Heart Association. J Am Coll Cardiol. 1999 Oct;34(4):1262–1347. doi: 10.1016/s0735-1097(99)00389-7. [DOI] [PubMed] [Google Scholar]
  30. Eglitis M. A., Dawson D., Park K. W., Mouradian M. M. Targeting of marrow-derived astrocytes to the ischemic brain. Neuroreport. 1999 Apr 26;10(6):1289–1292. doi: 10.1097/00001756-199904260-00025. [DOI] [PubMed] [Google Scholar]
  31. Elbashir S. M., Harborth J., Lendeckel W., Yalcin A., Weber K., Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001 May 24;411(6836):494–498. doi: 10.1038/35078107. [DOI] [PubMed] [Google Scholar]
  32. Eriksdotter Jönhagen M., Nordberg A., Amberla K., Bäckman L., Ebendal T., Meyerson B., Olson L., Seiger, Shigeta M., Theodorsson E. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 1998 Sep-Oct;9(5):246–257. doi: 10.1159/000017069. [DOI] [PubMed] [Google Scholar]
  33. Farlow Martin. A clinical overview of cholinesterase inhibitors in Alzheimer's disease. Int Psychogeriatr. 2002;14 (Suppl 1):93–126. doi: 10.1017/s1041610203008688. [DOI] [PubMed] [Google Scholar]
  34. Faulds D., Heel R. C. Ganciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in cytomegalovirus infections. Drugs. 1990 Apr;39(4):597–638. doi: 10.2165/00003495-199039040-00008. [DOI] [PubMed] [Google Scholar]
  35. Ferrara N., Houck K., Jakeman L., Leung D. W. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev. 1992 Feb;13(1):18–32. doi: 10.1210/edrv-13-1-18. [DOI] [PubMed] [Google Scholar]
  36. Flotte T., Carter B., Conrad C., Guggino W., Reynolds T., Rosenstein B., Taylor G., Walden S., Wetzel R. A phase I study of an adeno-associated virus-CFTR gene vector in adult CF patients with mild lung disease. Hum Gene Ther. 1996 Jun 10;7(9):1145–1159. doi: 10.1089/hum.1996.7.9-1145. [DOI] [PubMed] [Google Scholar]
  37. Flotte Terence R., Zeitlin Pamela L., Reynolds Thomas C., Heald Alison E., Pedersen Patty, Beck Suzanne, Conrad Carol K., Brass-Ernst Lois, Humphries Margaret, Sullivan Kevin. Phase I trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (rAAV2)-CFTR vector in adult cystic fibrosis patients: a two-part clinical study. Hum Gene Ther. 2003 Jul 20;14(11):1079–1088. doi: 10.1089/104303403322124792. [DOI] [PubMed] [Google Scholar]
  38. Freeman T. B., Sanberg P. R., Isacson O. Development of the human striatum: implications for fetal striatal transplantation in the treatment of Huntington's disease. Cell Transplant. 1995 Nov-Dec;4(6):539–545. doi: 10.1177/096368979500400604. [DOI] [PubMed] [Google Scholar]
  39. Friedmann T., Roblin R. Gene therapy for human genetic disease? Science. 1972 Mar 3;175(4025):949–955. doi: 10.1126/science.175.4025.949. [DOI] [PubMed] [Google Scholar]
  40. Goss James R., Goins William F., Lacomis David, Mata Marina, Glorioso Joseph C., Fink David J. Herpes simplex-mediated gene transfer of nerve growth factor protects against peripheral neuropathy in streptozotocin-induced diabetes in the mouse. Diabetes. 2002 Jul;51(7):2227–2232. doi: 10.2337/diabetes.51.7.2227. [DOI] [PubMed] [Google Scholar]
  41. Gossen M., Bonin A. L., Freundlieb S., Bujard H. Inducible gene expression systems for higher eukaryotic cells. Curr Opin Biotechnol. 1994 Oct;5(5):516–520. doi: 10.1016/0958-1669(94)90067-1. [DOI] [PubMed] [Google Scholar]
  42. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  43. Hacein-Bey-Abina S., Von Kalle C., Schmidt M., McCormack M. P., Wulffraat N., Leboulch P., Lim A., Osborne C. S., Pawliuk R., Morillon E. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003 Oct 17;302(5644):415–419. doi: 10.1126/science.1088547. [DOI] [PubMed] [Google Scholar]
  44. Hacein-Bey-Abina Salima, Fischer Alain, Cavazzana-Calvo Marina. Gene therapy of X-linked severe combined immunodeficiency. Int J Hematol. 2002 Nov;76(4):295–298. doi: 10.1007/BF02982686. [DOI] [PubMed] [Google Scholar]
  45. Hacein-Bey-Abina Salima, von Kalle Christof, Schmidt Manfred, Le Deist Françoise, Wulffraat Nicolas, McIntyre Elisabeth, Radford Isabelle, Villeval Jean-Luc, Fraser Christopher C., Cavazzana-Calvo Marina. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2003 Jan 16;348(3):255–256. doi: 10.1056/NEJM200301163480314. [DOI] [PubMed] [Google Scholar]
  46. Hammond S. M., Bernstein E., Beach D., Hannon G. J. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature. 2000 Mar 16;404(6775):293–296. doi: 10.1038/35005107. [DOI] [PubMed] [Google Scholar]
  47. Hannon Gregory J. RNA interference. Nature. 2002 Jul 11;418(6894):244–251. doi: 10.1038/418244a. [DOI] [PubMed] [Google Scholar]
  48. Hefti F. Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections. J Neurosci. 1986 Aug;6(8):2155–2162. doi: 10.1523/JNEUROSCI.06-08-02155.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Herman J. R., Adler H. L., Aguilar-Cordova E., Rojas-Martinez A., Woo S., Timme T. L., Wheeler T. M., Thompson T. C., Scardino P. T. In situ gene therapy for adenocarcinoma of the prostate: a phase I clinical trial. Hum Gene Ther. 1999 May 1;10(7):1239–1249. doi: 10.1089/10430349950018229. [DOI] [PubMed] [Google Scholar]
  50. Hommel Jonathan D., Sears Robert M., Georgescu Dan, Simmons Diana L., DiLeone Ralph J. Local gene knockdown in the brain using viral-mediated RNA interference. Nat Med. 2003 Nov 23;9(12):1539–1544. doi: 10.1038/nm964. [DOI] [PubMed] [Google Scholar]
  51. Horellou P., Brundin P., Kalén P., Mallet J., Björklund A. In vivo release of dopa and dopamine from genetically engineered cells grafted to the denervated rat striatum. Neuron. 1990 Oct;5(4):393–402. doi: 10.1016/0896-6273(90)90078-t. [DOI] [PubMed] [Google Scholar]
  52. Ikeda Y., Goto Y., Yonemitsu Y., Miyazaki M., Sakamoto T., Ishibashi T., Tabata T., Ueda Y., Hasegawa M., Tobimatsu S. Simian immunodeficiency virus-based lentivirus vector for retinal gene transfer: a preclinical safety study in adult rats. Gene Ther. 2003 Jul;10(14):1161–1169. doi: 10.1038/sj.gt.3301973. [DOI] [PubMed] [Google Scholar]
  53. Ilsley D. D., Lee S. H., Miller W. H., Kuchta R. D. Acyclic guanosine analogs inhibit DNA polymerases alpha, delta, and epsilon with very different potencies and have unique mechanisms of action. Biochemistry. 1995 Feb 28;34(8):2504–2510. doi: 10.1021/bi00008a014. [DOI] [PubMed] [Google Scholar]
  54. Isaacson L. G., Saffran B. N., Crutcher K. A. Intracerebral NGF infusion induces hyperinnervation of cerebral blood vessels. Neurobiol Aging. 1990 Jan-Feb;11(1):51–55. doi: 10.1016/0197-4580(90)90062-5. [DOI] [PubMed] [Google Scholar]
  55. Isacson O., Deacon T. W., Pakzaban P., Galpern W. R., Dinsmore J., Burns L. H. Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres. Nat Med. 1995 Nov;1(11):1189–1194. doi: 10.1038/nm1195-1189. [DOI] [PubMed] [Google Scholar]
  56. Ishikawa Fumihiko, Drake Christopher J., Yang Su, Fleming Paula, Minamiguchi Hitoshi, Visconti Richard P., Crosby Christopher V., Argraves W. Scott, Harada Mine, Key L. Lyndon., Jr Transplanted human cord blood cells give rise to hepatocytes in engrafted mice. Ann N Y Acad Sci. 2003 May;996:174–185. doi: 10.1111/j.1749-6632.2003.tb03245.x. [DOI] [PubMed] [Google Scholar]
  57. Johansson C. B., Momma S., Clarke D. L., Risling M., Lendahl U., Frisén J. Identification of a neural stem cell in the adult mammalian central nervous system. Cell. 1999 Jan 8;96(1):25–34. doi: 10.1016/s0092-8674(00)80956-3. [DOI] [PubMed] [Google Scholar]
  58. Johnson P. A., Miyanohara A., Levine F., Cahill T., Friedmann T. Cytotoxicity of a replication-defective mutant of herpes simplex virus type 1. J Virol. 1992 May;66(5):2952–2965. doi: 10.1128/jvi.66.5.2952-2965.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Kaplitt M. G., Leone P., Samulski R. J., Xiao X., Pfaff D. W., O'Malley K. L., During M. J. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat Genet. 1994 Oct;8(2):148–154. doi: 10.1038/ng1094-148. [DOI] [PubMed] [Google Scholar]
  60. Kawaja M. D., Gage F. H. Morphological and neurochemical features of cultured primary skin fibroblasts of Fischer 344 rats following striatal implantation. J Comp Neurol. 1992 Mar 1;317(1):102–116. doi: 10.1002/cne.903170108. [DOI] [PubMed] [Google Scholar]
  61. Klein G. The approaching era of the tumor suppressor genes. Science. 1987 Dec 11;238(4833):1539–1545. doi: 10.1126/science.3317834. [DOI] [PubMed] [Google Scholar]
  62. Knowles M. R., Noone P. G., Hohneker K., Johnson L. G., Boucher R. C., Efthimiou J., Crawford C., Brown R., Schwartzbach C., Pearlman R. A double-blind, placebo controlled, dose ranging study to evaluate the safety and biological efficacy of the lipid-DNA complex GR213487B in the nasal epithelium of adult patients with cystic fibrosis. Hum Gene Ther. 1998 Jan 20;9(2):249–269. doi: 10.1089/hum.1998.9.2-249. [DOI] [PubMed] [Google Scholar]
  63. Kochanek S., Schiedner G., Volpers C. High-capacity 'gutless' adenoviral vectors. Curr Opin Mol Ther. 2001 Oct;3(5):454–463. [PubMed] [Google Scholar]
  64. Kromer L. F. Nerve growth factor treatment after brain injury prevents neuronal death. Science. 1987 Jan 9;235(4785):214–216. doi: 10.1126/science.3798108. [DOI] [PubMed] [Google Scholar]
  65. LEVI-MONTALCINI R., HAMBURGER V. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J Exp Zool. 1951 Mar;116(2):321–361. doi: 10.1002/jez.1401160206. [DOI] [PubMed] [Google Scholar]
  66. Lang Frederick F., Bruner Janet M., Fuller Gregory N., Aldape Kenneth, Prados Michael D., Chang Susan, Berger Mitchel S., McDermott Michael W., Kunwar Sandeep M., Junck Larry R. Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: biological and clinical results. J Clin Oncol. 2003 Jul 1;21(13):2508–2518. doi: 10.1200/JCO.2003.21.13.2508. [DOI] [PubMed] [Google Scholar]
  67. Leifer Bennett P. Early diagnosis of Alzheimer's disease: clinical and economic benefits. J Am Geriatr Soc. 2003 May;51(5 Suppl DEMENTIA):S281–S288. doi: 10.1046/j.1532-5415.5153.x. [DOI] [PubMed] [Google Scholar]
  68. Lin Q., Cunningham L. A., Epstein L. G., Pechan P. A., Short M. P., Fleet C., Bohn M. C. Human fetal astrocytes as an ex vivo gene therapy vehicle for delivering biologically active nerve growth factor. Hum Gene Ther. 1997 Feb 10;8(3):331–339. doi: 10.1089/hum.1997.8.3-331. [DOI] [PubMed] [Google Scholar]
  69. Lindvall O., Brundin P., Widner H., Rehncrona S., Gustavii B., Frackowiak R., Leenders K. L., Sawle G., Rothwell J. C., Marsden C. D. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease. Science. 1990 Feb 2;247(4942):574–577. doi: 10.1126/science.2105529. [DOI] [PubMed] [Google Scholar]
  70. Lipardi C., Wei Q., Paterson B. M. RNAi as random degradative PCR: siRNA primers convert mRNA into dsRNAs that are degraded to generate new siRNAs. Cell. 2001 Nov 2;107(3):297–307. doi: 10.1016/s0092-8674(01)00537-2. [DOI] [PubMed] [Google Scholar]
  71. Liu Ge, Li DeShan, Pasumarthy Murali K., Kowalczyk Tomasz H., Gedeon Christopher R., Hyatt Susannah L., Payne Jennifer M., Miller Timothy J., Brunovskis Peter, Fink Tamara L. Nanoparticles of compacted DNA transfect postmitotic cells. J Biol Chem. 2003 Jun 14;278(35):32578–32586. doi: 10.1074/jbc.M305776200. [DOI] [PubMed] [Google Scholar]
  72. Lois C., Alvarez-Buylla A. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2074–2077. doi: 10.1073/pnas.90.5.2074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Mack C. A., Patel S. R., Schwarz E. A., Zanzonico P., Hahn R. T., Ilercil A., Devereux R. B., Goldsmith S. J., Christian T. F., Sanborn T. A. Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart. J Thorac Cardiovasc Surg. 1998 Jan;115(1):168–177. doi: 10.1016/s0022-5223(98)70455-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Mann C. J., Honeyman K., Cheng A. J., Ly T., Lloyd F., Fletcher S., Morgan J. E., Partridge T. A., Wilton S. D. Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse. Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):42–47. doi: 10.1073/pnas.011408598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Marshall E. Gene therapy death prompts review of adenovirus vector. Science. 1999 Dec 17;286(5448):2244–2245. doi: 10.1126/science.286.5448.2244. [DOI] [PubMed] [Google Scholar]
  76. Mendez Ivar, Dagher Alain, Hong Murray, Gaudet Paula, Weerasinghe Swarna, McAlister Vivian, King David, Desrosiers Jacques, Darvesh Sultan, Acorn Tanya. Simultaneous intrastriatal and intranigral fetal dopaminergic grafts in patients with Parkinson disease: a pilot study. Report of three cases. J Neurosurg. 2002 Mar;96(3):589–596. doi: 10.3171/jns.2002.96.3.0589. [DOI] [PubMed] [Google Scholar]
  77. Mercola K. E., Stang H. D., Browne J., Salser W., Cline M. J. Insertion of a new gene of viral origin into bone marrow cells of mice. Science. 1980 May 30;208(4447):1033–1035. doi: 10.1126/science.6246577. [DOI] [PubMed] [Google Scholar]
  78. Miller D. G., Adam M. A., Miller A. D. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol. 1990 Aug;10(8):4239–4242. doi: 10.1128/mcb.10.8.4239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Mitani K., Kubo S. Adenovirus as an integrating vector. Curr Gene Ther. 2002 May;2(2):135–144. doi: 10.2174/1566523024605591. [DOI] [PubMed] [Google Scholar]
  80. Molnar-Kimber K. L., Sterman D. H., Chang M., Kang E. H., ElBash M., Lanuti M., Elshami A., Gelfand K., Wilson J. M., Kaiser L. R. Impact of preexisting and induced humoral and cellular immune responses in an adenovirus-based gene therapy phase I clinical trial for localized mesothelioma. Hum Gene Ther. 1998 Sep 20;9(14):2121–2133. doi: 10.1089/hum.1998.9.14-2121. [DOI] [PubMed] [Google Scholar]
  81. Monahan Paul E., Jooss Karin, Sands Mark S. Safety of adeno-associated virus gene therapy vectors: a current evaluation. Expert Opin Drug Saf. 2002 May;1(1):79–91. doi: 10.1517/14740338.1.1.79. [DOI] [PubMed] [Google Scholar]
  82. Moolten F. L. An alternative to the magic bullet paradigm for specific cancer therapy. Med Hypotheses. 1987 Sep;24(1):43–51. doi: 10.1016/0306-9877(87)90045-4. [DOI] [PubMed] [Google Scholar]
  83. Moolten F. L. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res. 1986 Oct;46(10):5276–5281. [PubMed] [Google Scholar]
  84. Mulligan R. C., Berg P. Factors governing the expression of a bacterial gene in mammalian cells. Mol Cell Biol. 1981 May;1(5):449–459. doi: 10.1128/mcb.1.5.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Mulligan R. C., Berg P. Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2072–2076. doi: 10.1073/pnas.78.4.2072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Nigro J. M., Baker S. J., Preisinger A. C., Jessup J. M., Hostetter R., Cleary K., Bigner S. H., Davidson N., Baylin S., Devilee P. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. doi: 10.1038/342705a0. [DOI] [PubMed] [Google Scholar]
  87. Nobile C., Marchi J., Nigro V., Roberts R. G., Danieli G. A. Exon-intron organization of the human dystrophin gene. Genomics. 1997 Oct 15;45(2):421–424. doi: 10.1006/geno.1997.4911. [DOI] [PubMed] [Google Scholar]
  88. Nykänen A., Haley B., Zamore P. D. ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell. 2001 Nov 2;107(3):309–321. doi: 10.1016/s0092-8674(01)00547-5. [DOI] [PubMed] [Google Scholar]
  89. Ohlendieck K., Matsumura K., Ionasescu V. V., Towbin J. A., Bosch E. P., Weinstein S. L., Sernett S. W., Campbell K. P. Duchenne muscular dystrophy: deficiency of dystrophin-associated proteins in the sarcolemma. Neurology. 1993 Apr;43(4):795–800. doi: 10.1212/wnl.43.4.795. [DOI] [PubMed] [Google Scholar]
  90. Orlic Donald, Kajstura Jan, Chimenti Stefano, Bodine David M., Leri Annarosa, Anversa Piero. Bone marrow stem cells regenerate infarcted myocardium. Pediatr Transplant. 2003;7 (Suppl 3):86–88. doi: 10.1034/j.1399-3046.7.s3.13.x. [DOI] [PubMed] [Google Scholar]
  91. Owens Roland A. Second generation adeno-associated virus type 2-based gene therapy systems with the potential for preferential integration into AAVS1. Curr Gene Ther. 2002 May;2(2):145–159. doi: 10.2174/1566523024605627. [DOI] [PubMed] [Google Scholar]
  92. Pakzaban P., Deacon T. W., Burns L. H., Isacson O. Increased proportion of acetylcholinesterase-rich zones and improved morphological integration in host striatum of fetal grafts derived from the lateral but not the medial ganglionic eminence. Exp Brain Res. 1993;97(1):13–22. doi: 10.1007/BF00228813. [DOI] [PubMed] [Google Scholar]
  93. Palmer T. D., Rosman G. J., Osborne W. R., Miller A. D. Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1330–1334. doi: 10.1073/pnas.88.4.1330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Piccini P., Brooks D. J., Björklund A., Gunn R. N., Grasby P. M., Rimoldi O., Brundin P., Hagell P., Rehncrona S., Widner H. Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient. Nat Neurosci. 1999 Dec;2(12):1137–1140. doi: 10.1038/16060. [DOI] [PubMed] [Google Scholar]
  95. Piccini P., Lindvall O., Björklund A., Brundin P., Hagell P., Ceravolo R., Oertel W., Quinn N., Samuel M., Rehncrona S. Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts. Ann Neurol. 2000 Nov;48(5):689–695. [PubMed] [Google Scholar]
  96. Porteous D. J., Dorin J. R., McLachlan G., Davidson-Smith H., Davidson H., Stevenson B. J., Carothers A. D., Wallace W. A., Moralee S., Hoenes C. Evidence for safety and efficacy of DOTAP cationic liposome mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther. 1997 Mar;4(3):210–218. doi: 10.1038/sj.gt.3300390. [DOI] [PubMed] [Google Scholar]
  97. Pulkkanen K. J., Parkkinen J. J., Laukkanen J. M., Kettunen M. I., Tyynela K., Kauppinen R. A., Ala-Opas M. Y., Yla-Herttuala S. HSV-tk gene therapy for human renal cell carcinoma in nude mice. Cancer Gene Ther. 2001 Jul;8(7):529–536. doi: 10.1038/sj.cgt.7700342. [DOI] [PubMed] [Google Scholar]
  98. Rajagopalan Sanjay, Mohler Emile, 3rd, Lederman Robert J., Saucedo Jorge, Mendelsohn Farrell O., Olin Jeffrey, Blebea John, Goldman Corey, Trachtenberg Jeffrey D., Pressler Milton. Regional Angiogenesis with Vascular Endothelial Growth Factor (VEGF) in peripheral arterial disease: Design of the RAVE trial. Am Heart J. 2003 Jun;145(6):1114–1118. doi: 10.1016/S0002-8703(03)00102-9. [DOI] [PubMed] [Google Scholar]
  99. Rajagopalan Sanjay, Trachtenberg Jeffrey, Mohler Emile, Olin Jeffrey, McBride Scott, Pak Raphael, Rasmussen Henrik, Crystal Ronald. Phase I study of direct administration of a replication deficient adenovirus vector containing the vascular endothelial growth factor cDNA (CI-1023) to patients with claudication. Am J Cardiol. 2002 Sep 1;90(5):512–516. doi: 10.1016/s0002-9149(02)02524-9. [DOI] [PubMed] [Google Scholar]
  100. Ram Z., Culver K. W., Oshiro E. M., Viola J. J., DeVroom H. L., Otto E., Long Z., Chiang Y., McGarrity G. J., Muul L. M. Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells. Nat Med. 1997 Dec;3(12):1354–1361. doi: 10.1038/nm1297-1354. [DOI] [PubMed] [Google Scholar]
  101. Riordan J. R., Rommens J. M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J. L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. doi: 10.1126/science.2475911. [DOI] [PubMed] [Google Scholar]
  102. Rocca Paola, Cocuzza Elena, Marchiaro Livio, Bogetto Filippo. Donepezil in the treatment of Alzheimer's disease: long-term efficacy and safety. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Feb;26(2):369–373. doi: 10.1016/s0278-5846(01)00283-4. [DOI] [PubMed] [Google Scholar]
  103. Rogers S., Pfuderer P. Use of viruses as carriers of added genetic information. Nature. 1968 Aug 17;219(5155):749–751. doi: 10.1038/219749a0. [DOI] [PubMed] [Google Scholar]
  104. Romero Norma Beatriz, Benveniste Olivier, Payan Christine, Braun Serge, Squiban Patrick, Herson Serge, Fardeau Michel. Current protocol of a research phase I clinical trial of full-length dystrophin plasmid DNA in Duchenne/Becker muscular dystrophies. Part II: clinical protocol. Neuromuscul Disord. 2002 Oct;12 (Suppl 1):S45–S48. doi: 10.1016/s0960-8966(02)00081-0. [DOI] [PubMed] [Google Scholar]
  105. Rosengart T. K., Lee L. Y., Patel S. R., Sanborn T. A., Parikh M., Bergman G. W., Hachamovitch R., Szulc M., Kligfield P. D., Okin P. M. Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation. 1999 Aug 3;100(5):468–474. doi: 10.1161/01.cir.100.5.468. [DOI] [PubMed] [Google Scholar]
  106. Rubinson Douglas A., Dillon Christopher P., Kwiatkowski Adam V., Sievers Claudia, Yang Lili, Kopinja Johnny, Rooney Dina L., Zhang Mingdi, Ihrig Melanie M., McManus Michael T. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet. 2003 Feb 18;33(3):401–406. doi: 10.1038/ng1117. [DOI] [PubMed] [Google Scholar]
  107. Ryan Edmond A., Lakey Jonathan R. T., Paty Breay W., Imes Sharleen, Korbutt Gregory S., Kneteman Norman M., Bigam David, Rajotte Ray V., Shapiro A. M. James. Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes. 2002 Jul;51(7):2148–2157. doi: 10.2337/diabetes.51.7.2148. [DOI] [PubMed] [Google Scholar]
  108. Safi J., Jr, DiPaula A. F., Jr, Riccioni T., Kajstura J., Ambrosio G., Becker L. C., Anversa P., Capogrossi M. C. Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart. Microvasc Res. 1999 Nov;58(3):238–249. doi: 10.1006/mvre.1999.2165. [DOI] [PubMed] [Google Scholar]
  109. Sager R. Tumor suppressor genes: the puzzle and the promise. Science. 1989 Dec 15;246(4936):1406–1412. doi: 10.1126/science.2574499. [DOI] [PubMed] [Google Scholar]
  110. Selkirk S. M., Greenberg S. J., Plunkett R. J., Barone T. A., Lis A., Spence P. O. Syngeneic central nervous system transplantation of genetically transduced mature, adult astrocytes. Gene Ther. 2002 Apr;9(7):432–443. doi: 10.1038/sj.gt.3301643. [DOI] [PubMed] [Google Scholar]
  111. Shand N., Weber F., Mariani L., Bernstein M., Gianella-Borradori A., Long Z., Sorensen A. G., Barbier N. A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. GLI328 European-Canadian Study Group. Hum Gene Ther. 1999 Sep 20;10(14):2325–2335. doi: 10.1089/10430349950016979. [DOI] [PubMed] [Google Scholar]
  112. Shimotohno K., Temin H. M. Formation of infectious progeny virus after insertion of herpes simplex thymidine kinase gene into DNA of an avian retrovirus. Cell. 1981 Oct;26(1 Pt 1):67–77. doi: 10.1016/0092-8674(81)90034-9. [DOI] [PubMed] [Google Scholar]
  113. Sijen T., Fleenor J., Simmer F., Thijssen K. L., Parrish S., Timmons L., Plasterk R. H., Fire A. On the role of RNA amplification in dsRNA-triggered gene silencing. Cell. 2001 Nov 16;107(4):465–476. doi: 10.1016/s0092-8674(01)00576-1. [DOI] [PubMed] [Google Scholar]
  114. Silverberg E., Boring C. C., Squires T. S. Cancer statistics, 1990. CA Cancer J Clin. 1990 Jan-Feb;40(1):9–26. [PubMed] [Google Scholar]
  115. Smith D. E., Roberts J., Gage F. H., Tuszynski M. H. Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy. Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10893–10898. doi: 10.1073/pnas.96.19.10893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Solly Sounkary K., Trajcevski Stephane, Frisén Charlotte, Holzer Georg W., Nelson Elisabeth, Clerc Béatrice, Abordo-Adesida Evelyn, Castro Maria, Lowenstein Pedro, Klatzmann David. Replicative retroviral vectors for cancer gene therapy. Cancer Gene Ther. 2003 Jan;10(1):30–39. doi: 10.1038/sj.cgt.7700521. [DOI] [PubMed] [Google Scholar]
  117. Swisher Stephen G., Roth Jack A., Komaki Ritsuko, Gu Jian, Lee J. Jack, Hicks Marshall, Ro Jae Y., Hong Waun K., Merritt James A., Ahrar Kamaran. Induction of p53-regulated genes and tumor regression in lung cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy. Clin Cancer Res. 2003 Jan;9(1):93–101. [PubMed] [Google Scholar]
  118. Tabin C. J., Hoffmann J. W., Goff S. P., Weinberg R. A. Adaptation of a retrovirus as a eucaryotic vector transmitting the herpes simplex virus thymidine kinase gene. Mol Cell Biol. 1982 Apr;2(4):426–436. doi: 10.1128/mcb.2.4.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  119. Takeshita S., Zheng L. P., Brogi E., Kearney M., Pu L. Q., Bunting S., Ferrara N., Symes J. F., Isner J. M. Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest. 1994 Feb;93(2):662–670. doi: 10.1172/JCI117018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  120. Tariot P. N. Maintaining cognitive function in Alzheimer disease: how effective are current treatments? Alzheimer Dis Assoc Disord. 2001 Aug;15 (Suppl 1):S26–S33. doi: 10.1097/00002093-200108001-00005. [DOI] [PubMed] [Google Scholar]
  121. Temin H. M. Malignant transformation of cells by viruses. Perspect Biol Med. 1970 Autumn;14(1):11–26. doi: 10.1353/pbm.1970.0006. [DOI] [PubMed] [Google Scholar]
  122. Temin H. M. Mechanism of cell transformation by RNA tumor viruses. Annu Rev Microbiol. 1971;25:609–648. doi: 10.1146/annurev.mi.25.100171.003141. [DOI] [PubMed] [Google Scholar]
  123. Temin H. M. The DNA provirus hypothesis. Science. 1976 Jun 11;192(4244):1075–1080. doi: 10.1126/science.58444. [DOI] [PubMed] [Google Scholar]
  124. Thioudellet Christine, Blot Stéphane, Squiban Patrick, Fardeau Michel, Braun Serge. Current protocol of a research phase I clinical trial of full-length dystrophin plasmid DNA in Duchenne/Becker muscular dystrophies. Part I: rationale. Neuromuscul Disord. 2002 Oct;12 (Suppl 1):S49–S51. doi: 10.1016/s0960-8966(02)00082-2. [DOI] [PubMed] [Google Scholar]
  125. Thomas Clare E., Ehrhardt Anja, Kay Mark A. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet. 2003 May;4(5):346–358. doi: 10.1038/nrg1066. [DOI] [PubMed] [Google Scholar]
  126. Trask T. W., Trask R. P., Aguilar-Cordova E., Shine H. D., Wyde P. R., Goodman J. C., Hamilton W. J., Rojas-Martinez A., Chen S. H., Woo S. L. Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. Mol Ther. 2000 Feb;1(2):195–203. doi: 10.1006/mthe.2000.0030. [DOI] [PubMed] [Google Scholar]
  127. Tuszynski M. H., Roberts J., Senut M. C., U H. S., Gage F. H. Gene therapy in the adult primate brain: intraparenchymal grafts of cells genetically modified to produce nerve growth factor prevent cholinergic neuronal degeneration. Gene Ther. 1996 Apr;3(4):305–314. [PubMed] [Google Scholar]
  128. Tuszynski Mark H. Growth-factor gene therapy for neurodegenerative disorders. Lancet Neurol. 2002 May;1(1):51–57. doi: 10.1016/s1474-4422(02)00006-6. [DOI] [PubMed] [Google Scholar]
  129. Uchida Eriko, Mizuguchi Hiroyuki, Ishii-Watabe Akiko, Hayakawa Takao. Comparison of the efficiency and safety of non-viral vector-mediated gene transfer into a wide range of human cells. Biol Pharm Bull. 2002 Jul;25(7):891–897. doi: 10.1248/bpb.25.891. [DOI] [PubMed] [Google Scholar]
  130. Van den Haute Chris, Eggermont Kristel, Nuttin Bart, Debyser Zeger, Baekelandt Veerle. Lentiviral vector-mediated delivery of short hairpin RNA results in persistent knockdown of gene expression in mouse brain. Hum Gene Ther. 2003 Dec 10;14(18):1799–1807. doi: 10.1089/104303403322611809. [DOI] [PubMed] [Google Scholar]
  131. Vogel G. Gene therapy. FDA moves against Penn scientist. Science. 2000 Dec 15;290(5499):2049–2051. doi: 10.1126/science.290.5499.2049b. [DOI] [PubMed] [Google Scholar]
  132. Wade N. UCLA gene therapy racked by friendly fire. Science. 1980 Oct 31;210(4469):509–511. doi: 10.1126/science.6932738. [DOI] [PubMed] [Google Scholar]
  133. Wagner J. A., Reynolds T., Moran M. L., Moss R. B., Wine J. J., Flotte T. R., Gardner P. Efficient and persistent gene transfer of AAV-CFTR in maxillary sinus. Lancet. 1998 Jun 6;351(9117):1702–1703. doi: 10.1016/S0140-6736(05)77740-0. [DOI] [PubMed] [Google Scholar]
  134. Wagner John A., Nepomuceno Ilynn B., Messner Anna H., Moran Mary Lynn, Batson Eric P., Dimiceli Sue, Brown Byron W., Desch Julie K., Norbash Alexander M., Conrad Carol K. A phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies. Hum Gene Ther. 2002 Jul 20;13(11):1349–1359. doi: 10.1089/104303402760128577. [DOI] [PubMed] [Google Scholar]
  135. Wei C. M., Gibson M., Spear P. G., Scolnick E. M. Construction and isolation of a transmissible retrovirus containing the src gene of Harvey murine sarcoma virus and the thymidine kinase gene of herpes simplex virus type 1. J Virol. 1981 Sep;39(3):935–944. doi: 10.1128/jvi.39.3.935-944.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  136. Weinberg R. A. Oncogenes and tumor suppressor genes. CA Cancer J Clin. 1994 May-Jun;44(3):160–170. doi: 10.3322/canjclin.44.3.160. [DOI] [PubMed] [Google Scholar]
  137. Weir G. C., Bonner-Weir S., Leahy J. L. Islet mass and function in diabetes and transplantation. Diabetes. 1990 Apr;39(4):401–405. doi: 10.2337/diab.39.4.401. [DOI] [PubMed] [Google Scholar]
  138. Widner H., Tetrud J., Rehncrona S., Snow B., Brundin P., Gustavii B., Björklund A., Lindvall O., Langston J. W. Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) N Engl J Med. 1992 Nov 26;327(22):1556–1563. doi: 10.1056/NEJM199211263272203. [DOI] [PubMed] [Google Scholar]
  139. Wigler M., Pellicer A., Silverstein S., Axel R. Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell. 1978 Jul;14(3):725–731. doi: 10.1016/0092-8674(78)90254-4. [DOI] [PubMed] [Google Scholar]
  140. Williams L. R. Hypophagia is induced by intracerebroventricular administration of nerve growth factor. Exp Neurol. 1991 Jul;113(1):31–37. doi: 10.1016/0014-4886(91)90143-z. [DOI] [PubMed] [Google Scholar]
  141. Williams L. R., Varon S., Peterson G. M., Wictorin K., Fischer W., Bjorklund A., Gage F. H. Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9231–9235. doi: 10.1073/pnas.83.23.9231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  142. Yang Fang, Liu Yun-He, Yang Xiao-Ping, Xu Jiang, Kapke Alissa, Carretero Oscar A. Myocardial infarction and cardiac remodelling in mice. Exp Physiol. 2002 Sep;87(5):547–555. doi: 10.1113/eph8702385. [DOI] [PubMed] [Google Scholar]
  143. Yee J. K., Zaia J. A. Prospects for gene therapy using HIV-based vectors. Somat Cell Mol Genet. 2001 Nov;26(1-6):159–174. doi: 10.1023/a:1021034931852. [DOI] [PubMed] [Google Scholar]
  144. Zabner J., Cheng S. H., Meeker D., Launspach J., Balfour R., Perricone M. A., Morris J. E., Marshall J., Fasbender A., Smith A. E. Comparison of DNA-lipid complexes and DNA alone for gene transfer to cystic fibrosis airway epithelia in vivo. J Clin Invest. 1997 Sep 15;100(6):1529–1537. doi: 10.1172/JCI119676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  145. Zalzman Michal, Gupta Sanjeev, Giri Ranjit K., Berkovich Irina, Sappal Baljit S., Karnieli Ohad, Zern Mark A., Fleischer Norman, Efrat Shimon. Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. Proc Natl Acad Sci U S A. 2003 May 19;100(12):7253–7258. doi: 10.1073/pnas.1136854100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  146. Zamore P. D., Tuschl T., Sharp P. A., Bartel D. P. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell. 2000 Mar 31;101(1):25–33. doi: 10.1016/S0092-8674(00)80620-0. [DOI] [PubMed] [Google Scholar]
  147. Zeimet Alain G., Marth Christian. Why did p53 gene therapy fail in ovarian cancer? Lancet Oncol. 2003 Jul;4(7):415–422. doi: 10.1016/s1470-2045(03)01139-2. [DOI] [PubMed] [Google Scholar]
  148. Ziady Assem-Galal, Gedeon Christopher R., Muhammad Osman, Stillwell Virginia, Oette Sharon M., Fink Tamara L., Quan Will, Kowalczyk Tomasz H., Hyatt Susannah L., Payne Jennifer. Minimal toxicity of stabilized compacted DNA nanoparticles in the murine lung. Mol Ther. 2003 Dec;8(6):948–956. doi: 10.1016/j.ymthe.2003.09.002. [DOI] [PubMed] [Google Scholar]
  149. van Deutekom J. C., Bremmer-Bout M., Janson A. A., Ginjaar I. B., Baas F., den Dunnen J. T., van Ommen G. J. Antisense-induced exon skipping restores dystrophin expression in DMD patient derived muscle cells. Hum Mol Genet. 2001 Jul 15;10(15):1547–1554. doi: 10.1093/hmg/10.15.1547. [DOI] [PubMed] [Google Scholar]

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