{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:35:16Z","timestamp":1790973316891,"version":"4.1.0"},"reference-count":22,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5661","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2004,2,20]]},"abstract":"<jats:p>\n            Adult stem cells offer the potential to treat many diseases through a combination of ex vivo genetic manipulation and autologous transplantation. Mesenchymal stem cells (MSCs, also referred to as marrow stromal cells) are adult stem cells that can be isolated as proliferating, adherent cells from bones. MSCs can differentiate into multiple cell types present in several tissues, including bone, fat, cartilage, and muscle, making them ideal candidates for a variety of cell-based therapies. Here, we have used adeno-associated virus vectors to disrupt dominant-negative mutant\n            <jats:italic>COL1A1<\/jats:italic>\n            collagen genes in MSCs from individuals with the brittle bone disorder osteogenesis imperfecta, demonstrating successful gene targeting in adult human stem cells.\n          <\/jats:p>","DOI":"10.1126\/science.1088757","type":"journal-article","created":{"date-parts":[[2004,2,19]],"date-time":"2004-02-19T20:53:03Z","timestamp":1077223983000},"page":"1198-1201","source":"Crossref","is-referenced-by-count":233,"title":["Gene Targeting in Stem Cells from Individuals with Osteogenesis Imperfecta"],"prefix":"10.1126","volume":"303","author":[{"given":"Joel R.","family":"Chamberlain","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Schwarze","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Rong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roli K.","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt D.","family":"Hankenson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Pace","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Underwood","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kit M.","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sussman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Byers","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Pathology, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195\u20137720, USA."},{"name":"Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109\u20130486, USA."},{"name":"Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","first-page":"5241","year":"2000","unstructured":"P. H. Byers, in The Metabolic and Molecular Basis of Inherited Disease, C. R. Scriver, A. L. Beaudet, W. S. Sly, D. Valle, Eds. (McGraw-Hill, New York, 2000), pp. 5241\u20135286.","journal-title":"The Metabolic and Molecular Basis of Inherited Disease"},{"key":"e_1_3_1_3_2","first-page":"508","volume":"51","year":"1992","unstructured":"M. C. Willing, C. J. Pruchno, M. Atkinson, P. H. Byers, Am. J. Hum. Genet.51, 508 (1992).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1086\/301689","volume":"62","year":"1998","unstructured":"J. Korkkoet al., Am. J. Hum. Genet.62, 98 (1998).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/nbt0702-735","volume":"20","year":"2002","unstructured":"R. Hirata, J. Chamberlain, R. Dong, D. W. Russell, Nature Biotechnol.20, 735 (2002).","journal-title":"Nature Biotechnol."},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1016\/S0021-9258(18)89655-7","volume":"260","year":"1985","unstructured":"J. Bonadio, K. A. Holbrook, R. E. Gelinas, J. Jacob, P. H. Byers, J. Biol. Chem.260, 1734 (1985).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1006\/jmbi.1994.1199","volume":"236","year":"1994","unstructured":"M. Raghunath, P. Bruckner, B. Steinmann, J. Mol. Biol.236, 940 (1994).","journal-title":"J. Mol. Biol."},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/6529","volume":"5","year":"1999","unstructured":"E. M. Horwitzet al., Nature Med.5, 309 (1999).","journal-title":"Nature Med."},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","first-page":"8932","DOI":"10.1073\/pnas.132252399","volume":"99","year":"2002","unstructured":"E. M. Horwitz et al., Proc. Natl. Acad. Sci. U.S.A. 99, 8932 (2002).","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"e_1_3_1_10_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/1047-8477(91)90064-4","volume":"106","year":"1991","unstructured":"C. Ploetz, E. I. Zycband, D. E. Birk, J. Struct. Biol.106, 73 (1991).","journal-title":"J. Struct. Biol."},{"key":"e_1_3_1_11_2","first-page":"670","volume":"47","year":"1990","unstructured":"C. D. Constantinou, M. Pack, S. B. Young, D. J. Prockop, Am. J. Hum. Genet.47, 670 (1990).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/humu.1380010108","volume":"1","year":"1992","unstructured":"M. J. Edwards, R. J. Wenstrup, P. H. Byers, D. H. Cohn, Hum. Mutat.1, 47 (1992).","journal-title":"Hum. Mutat."},{"key":"e_1_3_1_13_2","first-page":"1034","volume":"46","year":"1990","unstructured":"G. A. Wallis, B. J. Starman, A. B. Zinn, P. H. Byers, Am. J. Hum. Genet.46, 1034 (1990).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1073\/pnas.95.3.1142","volume":"95","year":"1998","unstructured":"R. F. Pereiraet al., Proc. Natl. Acad. Sci. U.S.A.95, 1142 (1998).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1002\/jbmr.5650070809","volume":"7","year":"1992","unstructured":"N. S. Fedarko, M. Moerike, R. Brenner, P. G. Robey, U. Vetter, J. Bone Miner. Res.7, 921 (1992).","journal-title":"J. Bone Miner. Res."},{"key":"e_1_3_1_16_2","doi-asserted-by":"crossref","first-page":"7376","DOI":"10.1128\/JVI.73.9.7376-7380.1999","volume":"73","year":"1999","unstructured":"N. Inoue, R. K. Hirata, D. W. Russell, J. Virol.73, 7376 (1999).","journal-title":"J. Virol."},{"key":"e_1_3_1_17_2","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1006\/mthe.2001.0283","volume":"3","year":"2001","unstructured":"N. Inoue, R. Dong, R. K. Hirata, D. W. Russell, Mol. Ther.3, 526 (2001).","journal-title":"Mol. Ther."},{"key":"e_1_3_1_18_2","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/ng0498-325","volume":"18","year":"1998","unstructured":"D. W. Russell, R. K. Hirata, Nature Genet.18, 325 (1998).","journal-title":"Nature Genet."},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/jor.1100090504","volume":"9","year":"1991","unstructured":"A. I. Caplan, J. Orthop. Res.9, 641 (1991).","journal-title":"J. Orthop. Res."},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5411.143"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5309.71"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088547"},{"key":"e_1_3_1_23_2","unstructured":"We thank G. Priestley and T. Papayannopoulou for NOD\/SCID mice; S. Heimfeld for cadaveric bone marrow cells; C. Miller for EM; D. Chen for mutation analysis; C. Xu R. Dong and R. Newton for technical assistance; and T. Kyriakides for helpful discussions. This work was supported by grants from the U.S. National Institutes of Health the Children's Brittle Bone Foundation and the George F. Odland Research Fund."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1088757","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:39:27Z","timestamp":1704857967000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1088757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,2,20]]},"references-count":22,"journal-issue":{"issue":"5661","published-print":{"date-parts":[[2004,2,20]]}},"alternative-id":["10.1126\/science.1088757"],"URL":"https:\/\/doi.org\/10.1126\/science.1088757","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,2,20]]}}}