292 DEVELOPMENT OF A LUPUS ANTI-DNA ANTIBODY AS AN INTRACELLULAR DELIVERY VEHICLE FOR PROTEIN TRANSDUCTION OF MICRO-DYSTROPHIN. (1st January 2005)

• Record Type: Journal Article
• Authors: Weisbart, R. H.; Chan, G.; Wakelin, R.
• Is Part Of: Journal of investigative medicine. Volume 53:Number 1(2005)
• Page Start: S129
• Page End: S129
• Publication Date: 2005-01-01
• Subjects: Clinical medicine -- Periodicals; Medicine -- Research -- Periodicals; Medicine; Research -- United States; Clinical medicine; Medicine -- Research; Periodicals; 616.075
• DOI: 10.2310/6650.2005.00005.291
• Languages: English
• ISSNs: 1081-5589

Abstract

Abstract : Purpose: To produce the Fv fragment of a lupus anti-DNA autoantibody that selectively targets and penetrates skeletal muscle in vivo as a fusion protein with a micro-dystrophin for use as a non-viral delivery vehicle to transport micro-dystrophin into muscle cells. Methods: Fv-micro-dystrophin was produced as a secreted protein by transient transfection of Fv-micro-dystrophin cDNA in COS-7 cells and as a non-secreted protein by permanent transfection in Pichia pastoris. Results: Isolated Fv-micro-dystrophin was shown to be full-length by Western blot analysis. Fv-micro-dystrophin penetrated multiple cell lines in vitro and localized to the plasma membrane of a cell line with membrane beta-dystroglycan. In the absence of membrane beta-dystroglycan, it localized to the cytoplasm. Conclusion: Antibody-mediated transduction of micro-dystrophin into muscle cells is a potential therapy for dystrophin-deficient muscular dystrophies.