{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:53:09Z","timestamp":1777571589215,"version":"3.51.4"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[1994,10,1]],"date-time":"1994-10-01T00:00:00Z","timestamp":780969600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Genet"],"published-print":{"date-parts":[[1994,10]]},"DOI":"10.1038\/ng1094-148","type":"journal-article","created":{"date-parts":[[2004,8,18]],"date-time":"2004-08-18T21:10:41Z","timestamp":1092863441000},"page":"148-154","source":"Crossref","is-referenced-by-count":880,"title":["Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain"],"prefix":"10.1038","volume":"8","author":[{"given":"Michael G.","family":"Kaplitt","sequence":"first","affiliation":[]},{"given":"Paola","family":"Leone","sequence":"additional","affiliation":[]},{"given":"Richard J.","family":"Samulski","sequence":"additional","affiliation":[]},{"given":"Xiao","family":"Xiao","sequence":"additional","affiliation":[]},{"given":"Donald W.","family":"Pfaff","sequence":"additional","affiliation":[]},{"given":"Karen L.","family":"O'Malley","sequence":"additional","affiliation":[]},{"given":"Matthew J.","family":"During","sequence":"additional","affiliation":[]}],"member":"297","reference":[{"key":"BFng1094148_CR1","doi-asserted-by":"publisher","first-page":"4329","DOI":"10.1128\/MCB.10.8.4239","volume":"10","author":"DG Miller","year":"1990","unstructured":"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. Molec. cell. biol. 10, 4329\u20134242 (1990).","journal-title":"Molec. cell. biol."},{"key":"BFng1094148_CR2","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/0042-6822(88)90079-7","volume":"167","author":"DY Ho","year":"1988","unstructured":"Ho, D.Y. & Mocarski, E.S. B-galactosidase as a marker in the peripheral and neural tissues of the herpes-simplex virus-infected mouse. Virology 167, 279\u2013283 (1988).","journal-title":"Virology"},{"key":"BFng1094148_CR3","first-page":"203","volume":"3","author":"XO Breakefield","year":"1991","unstructured":"Breakefield, X.O. & Deluka, N.A. Herpes simplex virus for gene delivery to neurons. New Biol. 3, 203\u2013218 (1991).","journal-title":"New Biol."},{"key":"BFng1094148_CR4","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1126\/science.2994215","volume":"229","author":"B Rotzman","year":"1985","unstructured":"Rotzman, B. & Jenklns, F.J. Genetic engineering of novel genomes of large DNA viruses. Science 229, 1208\u20131214 (1985).","journal-title":"Science"},{"key":"BFng1094148_CR5","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1128\/JVI.66.5.2952-2965.1992","volume":"66","author":"PA Johnson","year":"1992","unstructured":"Johnson, P.A. et al. Cytotoxicrty of a replication defective mutant of herpes simplex virus 1. J. Virol. 66, 2952\u20132955 (1992).","journal-title":"J. Virol."},{"key":"BFng1094148_CR6","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1126\/science.8382374","volume":"259","author":"G Le Gal La Salle","year":"1993","unstructured":"Le Gal La Salle, G. et al. An adenovirus vector for gene transfer into neruons and glia in the brain. Science 259, 988\u2013990 (1993).","journal-title":"Science"},{"key":"BFng1094148_CR7","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/ng0393-224","volume":"3","author":"S Akli","year":"1993","unstructured":"Akli, S. et al. Transfer of a foreign into the brain using adenovirus vectors. Nature Genetics 3, 224\u2013228 (1993).","journal-title":"Nature Genetics"},{"key":"BFng1094148_CR8","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/ng0393-219","volume":"3","author":"BL Davidson","year":"1993","unstructured":"Davidson, B.L. et al. A model system for in vivo gene transfer into the central nervous system using an adenoviral vector. Nature Genet. 3, 219\u2013223 (1993).","journal-title":"Nature Genet."},{"key":"BFng1094148_CR9","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/0166-2236(93)90174-K","volume":"16","author":"RL Neve","year":"1993","unstructured":"Neve, R.L. Adenovirus vectors enter the brain. Trends Neurosci. 16, 251\u2013253 (1993).","journal-title":"Trends Neurosci."},{"key":"BFng1094148_CR10","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/0092-8674(82)90035-6","volume":"30","author":"RR Spaete","year":"1982","unstructured":"Spaete, R.R. & Frenkel, N. The herpes simplex virus amplicon: A new eucaryotic defective-virus cloning-amplifying vector. Cell. 30, 295\u2013304 (1982).","journal-title":"Cell."},{"key":"BFng1094148_CR11","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/0042-6822(85)90351-4","volume":"142","author":"AD Kwong","year":"1985","unstructured":"Kwong, A.D. & Frenkel, N. The herpes simplex virus amplicon IV. Effecient expression of a chimeric chicken ovalbumin gene amplified within defective virus genomes. Virology 142, 421\u2013425 (1985).","journal-title":"Virology"},{"key":"BFng1094148_CR12","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/1044-7431(91)90062-S","volume":"2","author":"MG Kaplitt","year":"1991","unstructured":"Kaplitt, M.G. et al. Expression of afunctional foreign gene in adult mammalian brain following in vivo transfer viaaherpes simplex virus type 1 defective viral vector. Molec. cell. Neurosci. 2, 320\u2013330 (1991).","journal-title":"Molec. cell. Neurosci."},{"key":"BFng1094148_CR13","doi-asserted-by":"publisher","first-page":"8979","DOI":"10.1073\/pnas.91.19.8979","volume":"19","author":"MG Kaplitt","year":"1994","unstructured":"Kaplitt, M.G. et al. Preproenkephalin promoter yields region-specific and long-term expression in adult brain following direct in vivo gene transfer via a defective herpes simplex viral vector. Proc. natn. Acad. Sci. U.S.A. 19, 8979\u20138983 (1994).","journal-title":"Proc. natn. Acad. Sci. U.S.A."},{"key":"BFng1094148_CR14","doi-asserted-by":"publisher","first-page":"3655","DOI":"10.1073\/pnas.90.8.3655","volume":"90","author":"DY Ho","year":"1993","unstructured":"Ho, D.Y., Mocarski, E.S. & Sapolsky, R.M. Altering central nervous system physiology with a defective herpes simplex virus vector expressing the glucose transporter gene. Proc. natn. Acad. Sci. USA. 90, 3655\u20133659 (1993).","journal-title":"Proc. natn. Acad. Sci. USA."},{"key":"BFng1094148_CR15","doi-asserted-by":"publisher","first-page":"8950","DOI":"10.1073\/pnas.87.22.8950","volume":"87","author":"AI Geller","year":"1990","unstructured":"Geller, A.I., Keyomarski, K., Bryan, J. & Pardee, A.B. An efficient deletion mutant packaging system for defective HSV-1 vectors; potential applications to neuronal physiology and human gene therapy. Proc. natn. Acad. Sci. U.S.A. 87, 8950\u20138954 (1990).","journal-title":"Proc. natn. Acad. Sci. U.S.A."},{"key":"BFng1094148_CR16","first-page":"407","volume":"26","author":"KI Bems","year":"1979","unstructured":"Bems, K.I. & Hauswirth, W.W. Adeno-associated viruses. Adv. Virus Res. 26, 407\u2013409 (1979).","journal-title":"Adv. Virus Res."},{"key":"BFng1094148_CR17","first-page":"97","volume":"158","author":"N Muzyczka","year":"1992","unstructured":"Muzyczka, N. Use of adeno-associated virus as a general transduction vector for mammalian cells. Curr. Top. Microbiol. Immunol. 158, 97\u2013129 (1992).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"BFng1094148_CR18","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.1128\/JVI.61.10.3096-3101.1987","volume":"61","author":"RJ Samulski","year":"1987","unstructured":"Samulski, R.J., Chang, L.-S. & Shenk, T. A recombinant plasmid from which an infectious adeno-associated virus genome can be excised in vitro and its use to study viral replication. J. Virol. 61, 3096\u20133101 (1987).","journal-title":"J. Virol."},{"key":"BFng1094148_CR19","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1128\/JVI.63.9.3822-3828.1989","volume":"63","author":"RJ Samulski","year":"1989","unstructured":"Samulski, R.J., Chang, L.-S. & Shenk, T. Helper-free stocks of adeno-associated viruses: normal integration does not require viral gene expression. J. Virol. 63, 3022\u20133828 (1989).","journal-title":"J. Virol."},{"key":"BFng1094148_CR20","volume-title":"Parkinson's disease","author":"MD Yahr","year":"1987","unstructured":"Yahr, M.D. & Bergmann, K.J. (eds) Parkinson's disease. (Raven Press, New York, 1987)."},{"key":"BFng1094148_CR21","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1001\/archneur.1969.00480160015001","volume":"21","author":"MD Yatir","year":"1969","unstructured":"Yatir, M.D. et al. Treatment of parkinsonism with levadopa. Arch. Neurol. 21, 343\u2013354 (1969).","journal-title":"Arch. Neurol."},{"key":"BFng1094148_CR22","doi-asserted-by":"publisher","first-page":"9011","DOI":"10.1073\/pnas.86.22.9011","volume":"86","author":"JA Wolff","year":"1989","unstructured":"Wolff, J.A. et al. Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson's Disease. Proc. natn. Acad. Sci. U.S.A. 86, 9011\u20139014 (1989).","journal-title":"Proc. natn. Acad. Sci. U.S.A."},{"key":"BFng1094148_CR23","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1002\/ana.410080508","volume":"8","author":"WJ Freed","year":"1987","unstructured":"Freed, W.J. et al. Resoration of dopaminergic function by grafting of fetal rat substantia nigrato the caudate nucleus: long-term behavioral, biochemical, and histochemical studies. Ann. Neurol. 8, 510\u2013519 (1987).","journal-title":"Ann. Neurol."},{"key":"BFng1094148_CR24","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/0896-6273(90)90078-T","volume":"5","author":"P Horrelou","year":"1990","unstructured":"Horrelou, P. et al. In vivo release of dopa and dopamine from genetically engineered cells grafted to the denervated rat striatum. Neuron 5, 393\u2013402 (1990).","journal-title":"Neuron"},{"key":"BFng1094148_CR25","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/362450a0","volume":"262","author":"S Jiao","year":"1993","unstructured":"Jiao, S., Gurevich, V. & Wolff, J.A. Long term correction of rat model of Parkinson's Disease by gene therapy. Nature 262, 450\u2013453 (1993).","journal-title":"Nature"},{"key":"BFng1094148_CR26","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/0092-8674(78)90148-4","volume":"13","author":"NC Jones","year":"1978","unstructured":"Jones, N.C. & Shenk, T.S. Isolation of deletion and substitution mutants of adenovirus type 5. Cell 13, 181\u2013188 (1978).","journal-title":"Cell"},{"key":"BFng1094148_CR27","first-page":"1239","volume":"139","author":"GJ Nuovo","year":"1991","unstructured":"Nuovo, G.J. et al. An improved technique for the in situ detection of DMA after polymerase chain reaction amplification. Am. J. Pathol. 139, 1239\u20131244, (1991).","journal-title":"Am. J. Pathol."},{"key":"BFng1094148_CR28","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1101\/gr.2.4.305","volume":"2","author":"GJ Nuovo","year":"1993","unstructured":"Nuovo, G.J. et al. Importance of different variables for enhancing in situ detection of PCR-amplified DNA. PCR Meth. Appl. 2, 305\u2013312 (1993).","journal-title":"PCR Meth. Appl."},{"key":"BFng1094148_CR29","doi-asserted-by":"publisher","first-page":"10613","DOI":"10.1073\/pnas.90.22.10613","volume":"90","author":"TR Flotte","year":"1993","unstructured":"Flotte, T.R. et al. Stable in vivo expression of the cystic fibrosistransmembrane conductance regulator with an adeno-associated virus vector. Proc. natn. Acad. Sci. U.S.A. 90, 10613\u201310617 (1993).","journal-title":"Proc. natn. Acad. Sci. U.S.A."},{"key":"BFng1094148_CR30","doi-asserted-by":"publisher","first-page":"6910","DOI":"10.1021\/bi00396a007","volume":"26","author":"KL O'Malley","year":"1987","unstructured":"O'Malley, K.L. et al. Isolation and characterization of the human tyrosine hydroxylase gene: Identification of 5\u2032 alternative splice sites responsible for multiple mRNAs. Biochemistry 26, 6910\u20136914 (1987).","journal-title":"Biochemistry"},{"key":"BFng1094148_CR31","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/0304-3940(87)90298-9","volume":"75","author":"M Dubach","year":"1990","unstructured":"Dubach, M. et al. Primate neostriatal neurons containing tyrosine hydroxylase: immunohistochemical evidence. Neurosci. Lett. 75, 205\u2013210 (1990).","journal-title":"Neurosci. Lett."},{"key":"BFng1094148_CR32","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/0006-8993(80)90871-9","volume":"195","author":"F Hefti","year":"1980","unstructured":"Hefti, F., Melamed, E. & Wurtman, R.J. Partial lesions of the dopaminergic nigrostriatal system in rat brain: Biochemical characterization. Brain Res. 195, 123\u2013127 (1980).","journal-title":"Brain Res."},{"key":"BFng1094148_CR33","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1016\/0024-3205(87)90315-8","volume":"40","author":"R Margraves","year":"1987","unstructured":"Margraves, R. & Freed, W.J. Chronic intrastriatal dopamine infusions in rats with unilateral lesions of the substantia nigra. Life Sci. 40, 959\u2013966 (1987).","journal-title":"Life Sci."},{"key":"BFng1094148_CR34","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1002\/ana.410080508","volume":"8","author":"WJ Freed","year":"1987","unstructured":"Freed, W.J. et al. Resoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: long-term behavioral, biochemical, and histochemical studies. Ann. Neurol. 8, 510\u2013519 (1987).","journal-title":"Ann. Neurol."},{"key":"BFng1094148_CR35","doi-asserted-by":"publisher","first-page":"3988","DOI":"10.1128\/MCB.8.10.3988","volume":"8","author":"JS Lebkowski","year":"1988","unstructured":"Lebkowski, J.S., McNally, M.M., Okarma, T.B. & Lerch, L.B. Adeno-associated virus: a vector system for efficient introduction and integration of DNA into a variety of mammalian cell types. Molec. cell. Biol. 8, 3988\u20133996 (1988).","journal-title":"Molec. cell. Biol."},{"key":"BFng1094148_CR36","doi-asserted-by":"publisher","first-page":"4626","DOI":"10.1073\/pnas.88.11.4626","volume":"88","author":"R Scharfmann","year":"1991","unstructured":"Scharfmann, R., Axelrod, J.H. & Verma, I.M. Long-term in vivo expression of retrovirus-mediated gene transfer in mouse fibroblast implants. Proc. natn. Acad. Sci. U.S.A. 88, 4626\u20134630 (1991).","journal-title":"Proc. natn. Acad. Sci. U.S.A."},{"key":"BFng1094148_CR37","doi-asserted-by":"publisher","first-page":"3941","DOI":"10.1002\/j.1460-2075.1991.tb04964.x","volume":"10","author":"RJ Samulski","year":"1991","unstructured":"Samulski, R.J. et al. Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J. 10, 3941\u20133950 (1991).","journal-title":"EMBO J."},{"key":"BFng1094148_CR38","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1128\/JVI.62.6.1963-1973.1988","volume":"62","author":"SK McLaughlin","year":"1988","unstructured":"McLaughlin, S.K. et al. Adeno-associated virus general transduction vectors: Analysis of proviral structures. J. Virol. 62, 1963\u20131973 (1988).","journal-title":"J. Virol."},{"key":"BFng1094148_CR39","unstructured":"Poole, S. et al. Gene transfer into hematopoietic stem cells using AAV vectors: targeted integration into chromosome 19. Blood. (in the press)."},{"key":"BFng1094148_CR40","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/0042-6822(73)90341-3","volume":"52","author":"FL Graham","year":"1973","unstructured":"Graham, F.L. & van der Eb, A.J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52, 456\u2013467 (1973).","journal-title":"Virology"},{"key":"BFng1094148_CR41","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1099\/0022-1317-36-1-59","volume":"36","author":"FL Graham","year":"1977","unstructured":"Graham, F.L., Smiley, J., Russell, W.C. & Nairn, R. Characterization of a human cell line transformed by DNA from human adenovirus type 5. J. gen. Virol. 36, 59\u201374 (1977).","journal-title":"J. gen. Virol."},{"key":"BFng1094148_CR42","volume-title":"The rat brain in stereotaxic coordinates","author":"G Paxinos","year":"1982","unstructured":"Paxinos, G. & Watson, C. The rat brain in stereotaxic coordinates. (Academic Press, Australia, 1982)."},{"key":"BFng1094148_CR43","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/0006-8993(89)90597-0","volume":"494","author":"DA Perese","year":"1989","unstructured":"Perese, D.A., Ulman, J., Viola, J., Ewing, S.E. & Bankiewicz, K.S. A 6-hydroxydopamine-induced selective parkinsonian rat model. Brain Res. 494, 285\u2013293 (1989).","journal-title":"Brain Res."},{"key":"BFng1094148_CR44","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0014-4886(92)90053-S","volume":"115","author":"MJ During","year":"1992","unstructured":"During, M.J. et al. Biochemical and behavioral recovery in a rodent model of Parkinson's Disease following stereotactic implantation of dopamine-containing liposomes. Exp. Neurol. 115, 193\u2013199 (1992).","journal-title":"Exp. Neurol."}],"container-title":["Nature Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ng1094-148","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ng1094-148.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ng1094-148.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T21:06:32Z","timestamp":1684443992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ng1094-148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,10]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1994,10]]}},"alternative-id":["BFng1094148"],"URL":"https:\/\/doi.org\/10.1038\/ng1094-148","relation":{},"ISSN":["1061-4036","1546-1718"],"issn-type":[{"value":"1061-4036","type":"print"},{"value":"1546-1718","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,10]]}}}