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 Chronic stress induces fatal organ dysfunctions via a new neural circuit
21.08.2017 | Hokkaido University

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>