Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jumping gene could provide non-viral alternative for gene therapy

27.09.2006
A jumping gene first identified in a cabbage-eating moth may one day provide a safer, target-specific alternative to viruses for gene therapy, researchers say.

They compared the ability of the four best-characterized jumping genes, or transposons, to insert themselves into a cell's DNA and produce a desired change, such as making the cell resistant to damage from radiation therapy.

They found the piggyBac transposon was five to 10 times better than the other circular pieces of DNA at making a home and a difference in several mammalian cell lines, including three human ones.

"If we want to add a therapeutic gene, we can put it within the transposon and use it to deliver the gene into the cell," says Dr. Joseph M. Kaminski, radiation oncologist at the Medical College of Georgia Cancer Center and a corresponding author on research published the week of Sept. 25 in the online Proceedings of the National Academy of Sciences Early Edition. "You can use these wherever retroviruses have been used."

... more about:
»Beauty »DNA »piggyBac »retroviruses

In addition to piggyBac, researchers looked at what was believed to be the most efficient transposon in mammalian cells, hyperactive Sleeping Beauty, first found "asleep" in fish. They also looked at Tol2, another fish transposon, and Mos1, found in insects.

The piggyBac transposon, which has close relatives in the human genome, is widely used to genetically modify insects. Sleeping Beauty has been used to correct hereditary diseases, including hemophilia, in a mouse model.

For this study, researchers used transposons to deliver an antibiotic-resistant gene. "It's a way of screening and seeing which transposon is better," Dr. Kaminski says. They found that while piggyBac might not work as efficiently as a virus, it put Sleeping Beauty to shame when it came to making cells antibiotic-resistant.

"Sleeping Beauty has captured the field as far as transposons to be used in mammals," says Dr. Stefan Moisyadi, molecular biologist, at the University of Hawaii and a corresponding author. "But by comparing different transposons, we showed Sleeping Beauty is far inferior to piggyBac."

Scientists have used viruses as a gene delivery mechanism for more than 20 years because of their adeptness at getting inside cells and inserting themselves in DNA. But efficiency comes at a price. Gene therapy trials have been halted because of major complications, including deaths. As examples, one patient died because of his immune response to an adenovirus and three children in another study developed leukemia because the virus inserted itself upstream of a cancer-causing gene.

"With viruses, you don't have control," says Dr. Kaminski. "People have tried to modify viruses for site-specific integration and have not been very successful. Once they get into the cell, they can insert wherever they want."

Dr. Kaminski's previous work, published in 2002 in The FASEB Journal, hypothesized that the integration site for transposons can be selected. "Typically, viruses and transposons will integrate anywhere along the genome," he says. "If they integrate anywhere, it can obviously cause harm. If we can target the integration, be able to insert the gene at a safe spot in the genome, that would be beneficial." He confirmed that targeting integration is possible in a paper he co-authored in 2005 also in The FASEB Journal. "We can do it in insects," says Dr. Moisyadi. "I think it's a short step to take it to a targeting mechanism we can use in humans."

Another clear benefit is that transposons are cheaper to produce and probably safer than viruses. For example, retroviruses use RNA to make DNA, an error-prone process that must occur before integration, Dr. Kaminski says. Also, viruses can't carry larger genes, such as the dystrophin gene, which could help correct muscular dystrophy. On the other hand, unlike retroviruses, transposons have to be coated with lipid to slip into cells.

Although piggyBac is not as successful as the virus at integrating into DNA, "we could potentially make a hyperactive version of piggyBac, like they did for Sleeping Beauty, which might be as good or better than retroviruses," Dr. Kaminski says. "I think we'll do it or somebody will. I think it's a safer method."

"At the moment, unless something new comes out, it's the only way to go because viruses have been killing people," says Dr. Moisyadi, who has avoided viruses in his transgenesis studies.

"One of our next goals is to use transposons to deliver a radio-protective gene, called manganese superoxide dismutase, to potentially protect normal tissue from radiation damage," Dr. Kaminski says.

In cancer, he suspects gene therapy will focus on this type of modification of normal tissue for protective purposes as well as manipulating the immune response. However, it has broad applications for correcting single gene disorders, such as hemophilia, sickle cell disease and muscular dystrophy.

Toni Baker | EurekAlert!
Further information:
http://www.mcg.edu

Further reports about: Beauty DNA piggyBac retroviruses

More articles from Life Sciences:

nachricht Embryonic development: How do limbs develop from cells?
18.05.2018 | Humboldt-Universität zu Berlin

nachricht Reading histone modifications, an oncoprotein is modified in return
18.05.2018 | American Society for Biochemistry and Molecular Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>