Abstract

The animal core provides a central mechanism by which consistent, high quality and cost effective access to and development of mouse genetic mutants for studies related to gene therapy and cystic fibrosis are provided. This core supports studies in primates that provide transitional data needed before human trials can be undertaken. It also facilitates training of investigators in the efficient use of animal models. This core focuses, in particular, on provision of CFTR mutant mice and mutant mice with targeted alterations of their immune/inflammatory response; these mice provide important models for studies related to gene transfer to the lung and chronic inflammation and injury in the lung, as seen in CF. Baboons are also provided as a large animal model for hematopoietic stem cell gene therapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
2P30DK047754-11
Application #
6774631
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (O1))
Project Start
2004-01-01
Project End
2008-12-31
Budget Start
2004-01-01
Budget End
2004-12-31
Support Year
11
Fiscal Year
2004
Total Cost
$88,078
Indirect Cost

  Institution

Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Murnane, R; Zhang, X B; Hukkanen, R R et al. (2011) Myelodysplasia in 2 pig-tailed macaques (Macaca nemestrina) associated with retroviral vector-mediated insertional mutagenesis and overexpression of HOXB4. Vet Pathol 48:999-1001
Metzger, Michael J; McConnell-Smith, Audrey; Stoddard, Barry L et al. (2011) Single-strand nicks induce homologous recombination with less toxicity than double-strand breaks using an AAV vector template. Nucleic Acids Res 39:926-35
Miller, A D; Metzger, M J (2011) APOBEC3-mediated hypermutation of retroviral vectors produced from some retrovirus packaging cell lines. Gene Ther 18:528-30
Halbert, C L; Metzger, M J; Lam, S-L et al. (2011) Capsid-expressing DNA in AAV vectors and its elimination by use of an oversize capsid gene for vector production. Gene Ther 18:411-7
Kiem, Hans-Peter; Ironside, Christina; Beard, Brian C et al. (2010) A retroviral vector common integration site between leupaxin and zinc finger protein 91 (ZFP91) observed in baboon hematopoietic repopulating cells. Exp Hematol 38:819-22, 822.e1-3
Trobridge, Grant D; Wu, Robert A; Hansen, Michael et al. (2010) Cocal-pseudotyped lentiviral vectors resist inactivation by human serum and efficiently transduce primate hematopoietic repopulating cells. Mol Ther 18:725-33
Becker, P S; Taylor, J A; Trobridge, G D et al. (2010) Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector. Gene Ther 17:1244-52
Doty, Raymond T; Sabo, Kathleen M; Chen, Jing et al. (2010) An all-feline retroviral packaging system for transduction of human cells. Hum Gene Ther 21:1019-27
Enssle, Joerg; Trobridge, Grant D; Keyser, Kirsten A et al. (2010) Stable marking and transgene expression without progression to monoclonality in canine long-term hematopoietic repopulating cells transduced with lentiviral vectors. Hum Gene Ther 21:397-403
Halbert, Christine L; Madtes, David K; Vaughan, Andrew E et al. (2010) Expression of human alpha1-antitrypsin in mice and dogs following AAV6 vector-mediated gene transfer to the lungs. Mol Ther 18:1165-72

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