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Science 20 February 2004:
Vol. 303. no. 5661, pp. 1198 - 1201
DOI: 10.1126/science.1088757
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Reports

Gene Targeting in Stem Cells from Individuals with Osteogenesis Imperfecta

Joel R. Chamberlain,1 Ulrike Schwarze,2 Pei-Rong Wang,1 Roli K. Hirata,1 Kurt D. Hankenson,4 James M. Pace,2 Robert A. Underwood,1 Kit M. Song,5 Michael Sussman,6 Peter H. Byers,1,2 David W. Russell1,3*

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 COL1A1 collagen genes in MSCs from individuals with the brittle bone disorder osteogenesis imperfecta, demonstrating successful gene targeting in adult human stem cells.

1 Department of Medicine, University of Washington, Seattle, WA 98195–7720, USA.
2 Department of Pathology, University of Washington, Seattle, WA 98195–7720, USA.
3 Department of Biochemistry, University of Washington, Seattle, WA 98195–7720, USA.
4 Department of Orthopaedic Surgery and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109–0486, USA.
5 Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA.
6 Shriner's Hospital, Portland, OR 97201, USA.

* To whom correspondence should be addressed. E-mail: drussell{at}u.washington.edu

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