making muscle wasting history

Gene transfer with plasmids is can be very advantageous and attractive to patients and biologist because non-viral gene transfer does not require the incoming DNA to be related with the host DNA, for the recombination of DNA to occur and be successful.

Plasmids are small circular DNA structures without protein, naked DNA, inside bacteria to which they mostly confer resistance against antibiotics.
After successful experiments in muscles cell cultures, with dystrophin mics and dogs, A first clinical trial, conducted by Serge Braun, started at the end of 2000 with 9 Duchenne and Becker patients, who were older than the age of 15, this was because of ethical issues. The plasmids solution was injected into one single muscle of the forearm. Some new full-length dystrophin appeared in up to 25% of the muscle fibers around the injected sites. There were no signs of an immune reaction, neither against the plasmid construction nor against the newly produced dystrophin. This phase-1 trial thus showed showed that gene transfer with naked DNA is safe.

Dr Jon Wolff – Johns Hopkins University USA

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.