"This trial demonstrates that gene therapy is no longer limited by the viruses we find in nature, and should usher in the next generation of viral delivery systems for human gene transfer," said senior study author R. Jude Samulski, PhD, professor of pharmacology and director of the Gene Therapy Center at UNC. The study appears online in the Nov. 8, 2011 issue of the journal Molecular Therapy.
Through gene therapy, scientists treat diseases by correcting a patient's faulty genes. Most of the time, this approach involves commandeering a natural system for infecting and introducing new genes into cells; thus, the virus. But even though there are lots of relatively innocuous viruses available for this purpose, none of them are perfectly suited for gene therapy.
Rather than rely on nature, Samulski and his colleagues decided to engineer their dream gene therapy virus in the laboratory. First they chose the adeno-associated virus or AAV, a small nonpathogenic virus that most humans are exposed to at some point in life. They then took their favorite attributes from different forms of AAV – such as AAV type 1's ability to sneak into muscle, and AAV type 2's safe track record – and combined them into one "chimeric" virus. In the first trial of this form of gene therapy, the investigators gave six boys with Duchenne muscular dystrophy (DMD) this new virus. An x-linked inherited disorder, DMD affects one in 4,000 newborn boys.
The virus was engineered to contain the dystrophin gene, which is missing in patients with muscular dystrophy and is the ultimate cause of the disease's progressive muscle weakness. The replacement genes were injected into the bicep in one arm and a placebo was injected into the other arm of each of the patients. The researchers were able to detect the new genes in all of the patients treated with the gene therapy, but no immunological response.
As they move on to the next phase of clinical trials, Samulski says they are carefully considering how best to administer the gene therapy vectors to patients. Delivering enough replacement genes to a therapeutic effect could require larger doses of virus, which in turn could elicit an unwanted immune response. So the researchers are exploring a number of different options, including using a new high pressure technique developed by William J. Powers, MD, professor and chair of neurology at UNC, reported last July in the same journal, to get the virus into muscle at lower doses.
Study co-authors from UNC include Dawn E. Bowles, PhD; Scott W.J. McPhee, PhD, MPH; Chengwen Li, PhD; Steven J. Gray, PhD; Jade J. Samulski, Angelique S. Camp, Juan Li, MD; Bing Wang, Paul E. Monahan, MD; Joshua C. Grieger, PhD; and Xiao Xiao, PhD.
The UNC research was funded by the National Institutes of Health, the Muscular Dystrophy Association and a grant from the Senator Paul D. Wellstone Muscular Dystropy Cooperative Research Center funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Les Lang | EurekAlert!
UIC researchers find unique organ-specific signature profiles for blood vessel cells
18.02.2020 | University of Illinois at Chicago
Remdesivir prevents MERS coronavirus disease in monkeys
14.02.2020 | NIH/National Institute of Allergy and Infectious Diseases
Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.
Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...
Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices
The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...
Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.
Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.
After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.
"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.
Superconductivity approaching room temperature may be possible in hydrogen-rich compounds at much lower pressures than previously expected
Reaching room-temperature superconductivity is one of the biggest dreams in physics. Its discovery would bring a technological revolution by providing...
12.02.2020 | Event News
16.01.2020 | Event News
15.01.2020 | Event News
18.02.2020 | Power and Electrical Engineering
18.02.2020 | Information Technology
18.02.2020 | Physics and Astronomy