Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Novel gene therapy approach shows promise


Vanderbilt University Medical Center investigators are reporting success with a novel gene therapy approach. Working with cells grown in the laboratory, the group is the first to repair a defective gene and demonstrate that the resulting protein product is functional, said Dr. Alfred L. George Jr., senior author of a study published Dec. 15 in the Journal of Clinical Investigation.

Although use of the approach in patients is still years in the future, the findings are an important step in showing that a particular method of gene repair is possible, said George, director of Vanderbilt’s division of Genetic Medicine.

"We have very solid evidence that we can repair messenger RNA (the copy of DNA that is used to manufacture proteins), and that the repair results in a protein that has normalized function," he said. "That’s a good sign and makes us optimistic about moving forward with this type of gene therapy strategy."

Gene therapy is a phrase that describes many different modes of gene-based treatments. The most widely used strategy seeks to put normal copies of a gene into cells with a defective gene. An alternative approach targets a defective gene for repair, either of the DNA itself or of the messenger RNA copy of the gene -- the strategy favored by George’s group. Repairing messenger RNA offers advantages over other types of gene therapy, George said, because it works specifically in cells that have messenger RNA copies of the gene. Cells that are not actively using the targeted gene will not contain any messenger RNA copies to be repaired.

"We think this approach may have a niche. It could be useful for any inherited disease, but it may have a special ability to correct a problem in a dominant disorder, George said.

The RNA repair method studied by George and colleagues employs molecules called ribozymes -- repair machines that can be engineered to correct a defect in a selected messenger RNA. The current work targets for repair a mutation that causes myotonia congenita, an inherited muscle disease with symptoms including muscle stiffness. Because myotonia congenita is not a debilitating disease, gene therapy may not be appropriate for some patients, George said, but the disease serves as an excellent model for testing ribozymes as potential gene therapeutics.

"We know a great deal about myotonia congenita," George said. "We know about the genetics and the physiology, and we have cell culture and animal models. We have many experimental armaments to study the disease."

In addition, George said, myotonia congenita provides a good test case for more severe inherited muscle diseases, such as muscular dystrophy and related disorders.

Myotonia congenita is caused by mutations in chloride channels -- donut-like pores that allow chloride ions to pass across the cell membrane. Because chloride channels are important participants in the contraction-relaxation cycle of skeletal muscle, defects in these proteins affect muscle relaxation and cause muscle stiffness.

Over 80 different myotonia congenita-associated chloride channel mutations have been identified, George said. His team targeted one of these for repair, a mutation that George and colleagues first identified in a Pennsylvania dog named Sparky.

Dr. Christopher Rogers, a former graduate student in George’s laboratory, engineered ribozymes to correct the "Sparky" defect and then introduced the ribozymes into cells harboring the mutant chloride channels. He demonstrated that the ribozymes could indeed repair the messenger RNA for the defective channels and that the resulting repaired proteins had normal chloride channel function. The repair was not effective in all cells, George said, but in a small percentage of cells, chloride channel function was completely restored.

"We know now that the ribozyme method can work; it’s effective at producing a protein with completely normal function," George said. "It would be nice if we knew it worked in the dog, and that’s the next step."

The investigators will continue studies in cells to improve the efficiency of the method before they test it in a group of Sparky’s descendants -- a dog model of myotonia congenita.

Other contributors to the Journal of Clinical Investigation study include Drs. Carlos G. Vanoye and Bruce A. Sullenger. The work was supported by the National Institutes of Health and the Muscular Dystrophy Association.

Leigh MacMillan | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

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...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

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...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

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...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

A new kind of quantum bits in two dimensions

19.03.2018 | Physics and Astronomy

Scientists have a new way to gauge the growth of nanowires

19.03.2018 | Materials Sciences

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Science & Research
Overview of more VideoLinks >>>