Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stanford researchers devise novel gene therapy technique

16.09.2002


Researchers at Stanford University Medical Center have devised a way to sneak DNA into skin cells taken from people with a potentially deadly genetic skin disorder. These modified cells later formed normal, healthy skin when transplanted onto the skin of mice. The technique, published in the advance online publication of the October issue of the journal Nature Medicine, marks the first time researchers have stably replaced the mutated gene in this disease and introduces a new gene therapy technique that could be useful in a wide range of diseases.



"We’re very hopeful," said study leader Paul Khavari, PhD, associate professor of dermatology at Stanford. "This study was performed in mice but it targets grafted human disease tissue."

The technique has advantages that could one day help it treat a variety of diseases. Not only can it accommodate large genes such as those responsible for Duchene’s muscular dystrophy and cystic fibrosis, but it causes the gene to integrate into human chromosomes in locations where it will continue to make protein as long as the cell is alive. In other techniques, the inserted DNA does not become part of the chromosome and eventually breaks down or else integrates in positions where the gene gets turned off.


Michele Calos, PhD, associate professor of genetics who developed the technique, said that although this paper is the first published report of her approach being used to treat one disease, early trials in other disease models look promising. "It worked great in this application and we hope it works just as well for other diseases," she said.

In the Nature Medicine paper, Khavari and Calos tested the new technique in a disease called recessive dystrophic epidermolysis bullosa (RDEB) in which the outer layer of skin is not firmly attached to the underlying layers. When children with RDEB encounter friction or trauma, the outer layer of skin simply peels away - even from such friction as a parent picking up the child. The children have severe blistering, scarring, infections, and often don’t live a normal life span.

Researchers know that RDEB is caused by a mutation in a single gene, whose protein - type-VII collagen - migrates to the lower side of the skin cell where it acts as a glue to anchor that cell in place. An ideal gene therapy for this disease would insert a copy of the gene into the skin cells where it could produce normal type-VII collagen. The problem is that the gene is too large to work in most standard gene therapy techniques.

Khavari thought that Calos’ technique would provide a way around the gene’s large size. "I’m excited that this approach has the potential to make gene therapy work in this disease and in a lot of cases where gene therapy hasn’t been working," Calos said.

Calos’ technique hijacks a mechanism used by a bacteria-infecting virus (called a bacteriophage) to integrate its genes into bacteria. The bacteriophage makes a protein called integrase that inserts a gene into a specific DNA sequence on the bacteria DNA. It turns out that humans also have a version of that DNA sequence. When the researchers insert a copy of the therapeutic gene and a gene coding for integrase into a human cell, the integrase inserts the gene into the human sequence.

To test Calos’ technique in RDEB, Susana Ortiz-Urda, PhD, a postdoctoral fellow in Khavari’s lab, took skin samples from four children with RDEB. The samples included skin stem cells that replenish the outer skin layer as it sloughs off. She then inserted the integrase DNA along with the gene that treats RDEB. In the lab dish, these cells all made normal levels of type-VII collagen.

Once the researchers established that the skin stem cells contained working type-VII collagen, they transplanted those cells onto mice where they formed normal skin tissue. The altered skin cells contained type-VII collagen in the proper location and looked like normal skin under the microscope. Although it has only been a few months since the mice received the transplants, Khavari said that the stem cells should exist throughout a person’s life and should provide a continuous supply of normal skin cells.

"This technique allows integration of therapeutic genes into stem cells, which supports long-term gene-delivery," Khavari said. However, both he and Calos warn that it could take many years for the technique to be tested well enough to be used in people. "The history of gene therapy shows that there are many steps that we have to take before bringing this to humans," Khavari said.

Michelle Brandt | EurekAlert!
Further information:
http://med-www.stanford.edu/MedCenter/MedSchool/
http://mednews.stanford.edu

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

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: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>