Abstract

application): The long term objective of this project is to develop methods for gene therapy of cystic fibrosis (CF). The project has two specific aims.
The first aim i s to identify the cells that express the cystic fibrosis transmembrane conductance regulator (CFTR) in the lung. This will be done by using monoclonal antibodies to CFTR. The second specific aim is to develop the molecular tools that are needed to deliver and stably express genes in those cells. The tissue specific expression of the polymeric immunoglobulin receptor (pIgR) will be used to target non-degradative internalization of macromolecules from the basolateral surface. A Fab fragment of antibody to pIgR covalently coupled to a polycation link to DNA will be used to direct foreign DNA into the desired cells. The specificity of the targeting will be determined and uptake and expression of the DNA optimized.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK043999-01
Application #
3245499
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1991-05-01
Project End
1996-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Day, Brian J; van Heeckeren, Anna M; Min, Elysia et al. (2004) Role for cystic fibrosis transmembrane conductance regulator protein in a glutathione response to bronchopulmonary pseudomonas infection. Infect Immun 72:2045-51
van Heeckeren, A M; Tscheikuna, J; Walenga, R W et al. (2000) Effect of Pseudomonas infection on weight loss, lung mechanics, and cytokines in mice. Am J Respir Crit Care Med 161:271-9
Ziady, A G; Ferkol, T; Dawson, D V et al. (1999) Chain length of the polylysine in receptor-targeted gene transfer complexes affects duration of reporter gene expression both in vitro and in vivo. J Biol Chem 274:4908-16
Ziady, A G; Ferkol, T; Gerken, T et al. (1998) Ligand substitution of receptor targeted DNA complexes affects gene transfer into hepatoma cells. Gene Ther 5:1685-97
Kaetzel, C S; Blanch, V J; Hempen, P M et al. (1997) The polymeric immunoglobulin receptor: structure and synthesis. Biochem Soc Trans 25:475-80
Piskurich, J F; Youngman, K R; Phillips, K M et al. (1997) Transcriptional regulation of the human polymeric immunoglobulin receptor gene by interferon-gamma. Mol Immunol 34:75-91
Ziady, A G; Perales, J C; Ferkol, T et al. (1997) Gene transfer into hepatoma cell lines via the serpin enzyme complex receptor. Am J Physiol 273:G545-52
Ferkol, T; Pellicena-Palle, A; Eckman, E et al. (1996) Immunologic responses to gene transfer into mice via the polymeric immunoglobulin receptor. Gene Ther 3:669-78
Eckman, E A; Cotton, C U; Kube, D M et al. (1995) Dietary changes improve survival of CFTR S489X homozygous mutant mouse. Am J Physiol 269:L625-30
Tamer, C M; Lamm, M E; Robinson, J K et al. (1995) Comparative studies of transcytosis and assembly of secretory IgA in Madin-Darby canine kidney cells expressing human polymeric Ig receptor. J Immunol 155:707-14

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