{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:37:13Z","timestamp":1790861833765,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,4,30]]},"abstract":"<jats:p>Gene transfer vectors based on lentiviruses can transduce terminally differentiated cells in the brain; however, their ability to reverse established behavioral deficits in animal models of neurodegeneration has not previously been tested. When recombinant feline immunodeficiency virus (FIV)-based vectors expressing \u03b2-glucuronidase were unilaterally injected into the striatum of adult \u03b2-glucuronidase deficient [mucopolysaccharidosis type VII (MPS VII)] mice, an animal model of lysosomal storage disease, there was bihemispheric correction of the characteristic cellular pathology. Moreover, after the injection of FIV-based vectors expressing \u03b2-glucuronidase into brains of \u03b2-glucuronidase-deficient mice with established impairments in spatial learning and memory, there was dramatic recovery of behavioral function. Cognitive improvement resulting from expression of \u03b2-glucuronidase was associated with alteration in expression of genes associated with neuronal plasticity. These data suggest that enzyme replacement to the MPS VII central nervous system goes beyond restoration of \u03b2-glucuronidase activity in the lysosome, and imparts improvements in plasticity and spatial learning.<\/jats:p>","DOI":"10.1073\/pnas.082011999","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T18:26:28Z","timestamp":1027880788000},"page":"6216-6221","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":135,"title":["Functional correction of established central nervous system deficits in an animal model of lysosomal storage disease with feline immunodeficiency virus-based vectors"],"prefix":"10.1073","volume":"99","author":[{"given":"Andrew I.","family":"Brooks","sequence":"first","affiliation":[{"name":"Departments of Internal Medicine, Neurology, Physiology and Biophysics, Neurosurgery, and Pediatrics, University of Iowa Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 52242; Department of Environmental Medicine, Centers for Functional Genomics, and Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642; and Chiron Technologies, Center for Gene Therapy, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen S.","family":"Stein","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Neurology, Physiology and Biophysics, Neurosurgery, and Pediatrics, University of Iowa Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 52242; Department of Environmental Medicine, Centers for Functional Genomics, and Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642; and Chiron Technologies, Center for Gene Therapy, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Neurology, Physiology and Biophysics, Neurosurgery, and Pediatrics, University of Iowa Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 52242; Department of Environmental Medicine, Centers for Functional Genomics, and Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642; and Chiron Technologies, Center for Gene Therapy, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Heth","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Neurology, Physiology and Biophysics, Neurosurgery, and Pediatrics, University of Iowa Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 52242; Department of Environmental Medicine, Centers for Functional Genomics, and Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642; and Chiron Technologies, Center for Gene Therapy, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Paul M.","family":"McCray","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Neurology, Physiology and Biophysics, Neurosurgery, and Pediatrics, University of Iowa Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 52242; Department of Environmental Medicine, Centers for Functional Genomics, and Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642; and Chiron Technologies, Center for Gene Therapy, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sybille L.","family":"Sauter","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Neurology, Physiology and Biophysics, Neurosurgery, and Pediatrics, University of Iowa Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 52242; Department of Environmental Medicine, Centers for Functional Genomics, and Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642; and Chiron Technologies, Center for Gene Therapy, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie C.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Neurology, Physiology and Biophysics, Neurosurgery, and Pediatrics, University of Iowa Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 52242; Department of Environmental Medicine, Centers for Functional Genomics, and Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642; and Chiron Technologies, Center for Gene Therapy, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Cory-Slechta","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Neurology, Physiology and Biophysics, Neurosurgery, and Pediatrics, University of Iowa Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 52242; Department of Environmental Medicine, Centers for Functional Genomics, and Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642; and Chiron Technologies, Center for Gene Therapy, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard J.","family":"Federoff","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Neurology, Physiology and Biophysics, Neurosurgery, and Pediatrics, University of Iowa Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 52242; Department of Environmental Medicine, Centers for Functional Genomics, and Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642; and Chiron Technologies, Center for Gene Therapy, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly L.","family":"Davidson","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Neurology, Physiology and Biophysics, Neurosurgery, and Pediatrics, University of Iowa Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 52242; Department of Environmental Medicine, Centers for Functional Genomics, and Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642; and Chiron Technologies, Center for Gene Therapy, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,4,16]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(73)80162-3"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114010"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.14.6567"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1998.9.16-2331"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.4.3424-3429.1999"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7205"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2296"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430340050015194"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/374367a0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1993.1067"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199312000-00028"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.11.3081.3081"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1773"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119322"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2001.0274"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/85454"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.3.249"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7176"},{"key":"e_1_3_3_19_2","first-page":"1","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Franklin K B J","year":"1997","unstructured":"K B J Franklin, G Paxinos The Mouse Brain in Stereotaxic Coordinates (Academic, San Diego), pp. 1\u2013190 (1997)."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.6.4991-5000.1999"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1994.1028"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.20.9564"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.9.6641-6649.1997"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1006\/nlme.1999.3951"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1089\/104303400750038453"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.230169397"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091062498"},{"key":"e_1_3_3_28_2","volume-title":"User Bulletin #2. ABI Prism 7700 Sequence Detection System","year":"1997","unstructured":"User Bulletin #2. ABI Prism 7700 Sequence Detection System, Technical Notes (Perkin\u2013Elmer, St. Pete Beach, FL), pp. 1\u201335. (1997)."},{"key":"e_1_3_3_29_2","first-page":"213","volume":"194","author":"Yamamoto J K","year":"1989","unstructured":"J K Yamamoto, H Hansen, E W Ho, T Y Morishita, T Okuda, T R Sawa, R M Nakamura, N C Pedersen J Am Vet Med Assoc 194, 213\u2013220 (1989).","journal-title":"J Am Vet Med Assoc"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1609"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.10.6181-6185.1992"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.1.608-617.1999"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117434"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80312-8"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0250169"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-01-00084.2001"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.47.31345"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)01993-X"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00282-3"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003053200"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058783"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.153.7.1403"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-04-01324.1999"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.082011999","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:11:07Z","timestamp":1649787067000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.082011999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,4,16]]},"references-count":43,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2002,4,30]]}},"alternative-id":["10.1073\/pnas.082011999"],"URL":"https:\/\/doi.org\/10.1073\/pnas.082011999","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,4,16]]},"assertion":[{"value":"2002-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}