Instead of the common gene therapy approach of adding new genetic material to "override" the faulty gene, the Duke scientists have developed a way to change the existing mutated gene responsible for the disorder into a normally functioning gene. The Duke researchers believe their approach could be safer and more stable than current methods of gene therapy.
The researchers are now conducting further tests of this new approach in animal models of the disease.
Duchenne muscular dystrophy is a genetic disease affecting one in 3,600 newborn males. The genetic mutation is found on the X chromosome, of which males have only one copy. (Females, with two X chromosomes, presumably have at least one good copy of the gene.)
Patients with Duchenne muscular dystrophy cannot produce the protein known as dystrophin, which is essential in maintaining the structural integrity of muscle fibers. Over time, patients with the disorder suffer gradual muscle deterioration, which leads to paralysis and eventual death, usually by age 25.
"Conventional genetic approaches to treating the disease involve adding normal genes to compensate for the mutated genes," said Charles Gersbach, assistant professor of biomedical engineering at Duke's Pratt School of Engineering and Department of Orthopaedic Surgery and member of Duke's Institute for Genome Sciences and Policy. "However, this can cause other unforeseen problems, or the beneficial effect does not always last very long.
"Our approach actually repairs the faulty gene, which is a lot simpler," said David Ousterout, the Duke biomedical engineering graduate student in the Gersbach lab who led the work. "It finds the faulty gene, and fixes it so it can start producing a functional protein again."
The results of the Duke study were published online in Molecular Therapy, the journal of the American Society for Gene and Cell Therapy. The project was supported by the Hartwell Foundation, the March of Dimes Foundation and the National Institutes of Health.
The Duke experiments, which were carried out in cell samples from Duchenne muscular dystrophy patients, were made possible by using a new technology for building synthetic proteins known as transcription activator-like effector nucleases (TALENs), which are artificial enzymes that can be engineered to bind to and modify almost any gene sequence.
These TALENs bind to the defective gene, and can correct the mutation to create a normally functioning gene.
"There is currently no effective treatment for this disease," Gersbach said. "Patients usually are in a wheelchair by the age of ten and many die in their late teens or early twenties."
Duchenne muscular dystrophy has been extensively studied by scientists, and it is believed that more than 60 percent of patients with this type of mutation can be treated with this novel genetic approach.
"Previous studies indicate that restoring the production of dystrophin proteins will be highly functional and alleviate disease symptoms when expressed in skeletal muscle tissue," said Ousterout.
Similar approaches could be helpful in treating other genetic diseases where a few gene mutations are responsible, such as sickle cell disease, hemophilia, or other muscular dystrophies, Gersbach said.
Other members of the team were Duke's Pablo Perez-Pinera, Pratiksha Thakore, Ami Kabadi, Matthew Brown, Xiaoxia Qin, and Olivier Fedrigo. Other participants were Vincent Mouly, Universite Pierre at Marie Curie, Paris, and Jacques Tremblay, Universite Laval, Quebec.
Citation: "Reading frame correction by targeted genome editing restores dystrophin expression in cells from Duchenne muscular dystrophy patients," David Ousterout, et. al, Molecular Therapy, DOI 10.1038/mt.2013.111
Richard Merritt | EurekAlert!
Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences
Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...
The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...
At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.
When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...
At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.
Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...
16.03.2018 | Event News
13.03.2018 | Event News
08.03.2018 | Event News
16.03.2018 | Earth Sciences
16.03.2018 | Physics and Astronomy
16.03.2018 | Life Sciences