Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stanford researchers develop gene therapy technique that sharply cuts risks

14.10.2002


Researchers at Stanford University Medical Center have devised a new gene therapy technique that appears to eliminate one of the major health risks linked to gene therapy. The technique, published in the Oct. 15 advanced online edition of the journal Nature Biotechnology, overcomes the need for viral vectors that have plagued gene therapy trials, while retaining the ability to insert therapeutic DNA into specific sites in the chromosomes.



"Our approach provides an alternative that didn’t exist before," said Michele Calos, PhD, associate professor of genetics at the School of Medicine and lead author on the study.

The goal of gene therapy is to insert a healthy copy of a gene into a cell where it can take over for a faulty version. If the therapeutic DNA does not integrate into the human chromosome, it produces its protein for a short time before being turned off or broken down within the cell. For a long-term cure, the gene has to wedge itself into a chromosome where it remains indefinitely integrated, getting passed on when the cell divides.


Current gene therapy approaches that cause genes to integrate use a viral vector to sneak the therapeutic DNA into the host cell, Calos said. However, the DNA inserts itself into the chromosome at random positions. In one recent French gene therapy trial, the randomly inserted DNA apparently activated a neighboring oncogene, causing a patient to develop leukemia. "That sort of puts another cloud over the existing gene therapy trials," Calos said.

Calos’ technique avoids the pitfalls of other gene therapy approaches by integrating DNA without using viral vectors, inserting the DNA at known locations. This new technique can also handle genes that are too large to fit into a viral package, such as the gene for Duchenne’s muscular dystrophy, Calos said.

In developing this new approach, Calos hijacked 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 the viral genes into a specific DNA sequence on the bacteria chromosome. 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 within the human sequence.

Calos and members of her lab, in collaboration with Mark Kay, MD, PhD, professor of pediatrics and genetics, tested the technique using a gene that makes Factor IX - a protein that is missing in the blood of people with one form of hemophilia. They injected mice with a piece of DNA containing the Factor IX gene plus a stretch of DNA that acts as an "insert me" signal to integrase. At the same time they injected a gene for integrase.

Within a week, mice that received this injection made 12 times more Factor IX than their littermates that received the injection without the integrase. Further experiments confirmed that the Factor IX gene had successfully integrated into the mouse DNA.

Although the mouse genome contains at least 53 potential integration sites, Calos and her team found the Factor IX gene in only two locations, with one location by far the more common. She said that for each tissue there may be a particular site that is the most likely insertion point. Her group is testing the technique in different tissue types to ensure that no human integration site is near a potential oncogene. "We need to look in different tissues to see where the hot spot is," Calos said.

Calos is also modifying the integrase so it targets specific integration sites that her team knows are safe. "We mutated the enzyme and evolved it so it will prefer one place over another," she said.

Calos said this approach should be effective for treating diseases in several different human organs including skin, retina, blood, muscle and lung. She hopes to start human trials for the technique in a fatal childhood skin disease called recessive dystrophic epidermolysis bullosa, which she has already treated in mice. "If that trial shows that it is safe then that will open the door for trials in other diseases," Calos said. She has collaborations underway testing the technique for use in Duchenne’s muscular dystrophy and cystic fibrosis, among others.


Contributing researchers to the study include Stanford graduate students Eric Olivares and Thomas Chalberg, and post-doctoral scholar Roger Hollis, PhD.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford.

Amy Adams | EurekAlert!
Further information:
http://mednews.stanford.edu

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

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: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>