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 Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>