Jon A. Wolff MD, Johns Hopkins Professor of Pediatrics and Medical Genetics Contact Information Waisman Center UW-Madison 1500 Highland Avenue Madison, WI 53705 (608) 263-5993 (608) 263-0530 jwolff@facstaff.wisc.edu 2-MBADD - A guide for Hmong families Know to Grow PKU Curriculum

The aim of Dr. Jon Wolff’s current research is to develop and refine the ability to directly deliver plasmid DNA into muscle, liver and other tissues through further development of the basic scientific knowledge of how plasmid DNA traverses cell membranes, enters nuclei and attains stable expression. Dr Wolff has grants to develop and evaluate the delivery of “naked DNA” to muscle cells via an intravascular route and to identify peptides that prolong the circulation of gene vectors in the blood and enable targeting to specific tissues. Dr. Wolff's data show that plasmid DNA can be delivered via a blood vessel into more than 10% of the muscle cells throughout the leg of a rat. This percentage of transfected muscle cells approaches the critical minimum percentage necessary to be curative in children with Duchenne muscular dystrophy. With this approach, multiple administrations should be possible, ensuring that a sufficient number of cells would express functional dystrophin, the missing protein in people with Duchenne muscular dystrophy. Dr. Wolff’s studies also indicate that this approach should lead to stable expression of the gene. Work is now underway to extend this approach to larger animals. If successful in larger animals, a human clinical trial in patients with Duchenne muscular dystrophy could begin in the near future. In addition, work is underway to extend the intravascular gene delivery method to other organs, with a current emphasis on promoting stable gene expression in liver. Sokoloff A, Bock I, Zhang G, Sebestyen MG, Wolff JA. The interactions of peptides with the innate immune system studied with T7 phage peptide display. Molecular Therapy 2(2):131-139, 2000. Herweijer H., Zhang G, Subbotin VM, Budker V, Williams P, and Wolff JA. Time course of gene expression after plasmid DNA gene transfer to the liver. Journal of Gene Medicine, 3:280-291, 2001. Zhang G, Budker V, Williams P, Subbotin V and Wolff JA: Efficient expression of naked DNA delivered intraarterially to limb muscles of nonhuman primates. Human Gene Therapy, 12:427-438, 2001. Sokoloff AV, Bock I, Zhang G, Hoffman S, Dama J, Ludtke JJ, Cooke AM and Wolff JA. Specific recognition of protein carboxy-erminal sequences by natural IgM antibodies in normal serum. Molecular Therapy (3) 6:821-830, 2001. Click to search National Library of Medicine and PubMed for other publications by Dr. Wolff

Relevant Web Sites:

• The Journal of Gene Medicine Clinical Trial Site

7/31/2004 by rowley@waisman.wisc.edu