Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cedars-Sinai researchers demonstrate a new way to switch therapeutic genes ’on’ and ’off’

23.12.2005


Novel signaling system may eventually help make gene therapies more effective



A gene therapy research team at Cedars-Sinai Medical Center has developed a new method of signaling therapeutic genes to turn "off" or "on," a mechanism that could enable scientists to fine-tune genetic- and stem cell-based therapies so that they are safer, more controllable and more effective.

Although other similar signaling systems have been developed, the Cedars-Sinai research is the first to give physicians the flexibility to arbitrarily turn the gene expression on or off even in the presence of an immune response to adenovirus, as would be present in most patients undergoing clinical trials. This has been a major obstacle in bringing the testing of genetic therapies to humans in a clinical setting.


As reported in a study published in the January issue of the Journal of Virology, the development of a new delivery system that can more effectively regulate therapeutic gene expression has important implications for efforts to advance gene and stem cell therapy strategies that may ultimately be used to treat life-threatening neurodegenerative diseases in the clinical setting. The study, which involved laboratory rats, focused on the area of the brain that has already been the target for research into genetic therapies for Parkinson’s disease.

"Since some diseases treated with gene therapy will require constant therapeutic expression while others may have periods of remission and therefore only require treatment during ’active’ disease states, a system that can more closely monitor the ’how much’ and ’when’ the therapeutic gene is produced is a critically important tool in the development of gene therapy treatments that could help people suffering from Parkinson’s and other diseases," said Maria Castro, Ph.D., co-director of the Board of Governors’ Gene Therapeutic Research Institute at Cedars-Sinai and lead author of the study.

"Until now, researchers working to develop successful gene therapy for diseases such as Parkinson’s have hit roadblocks such as toxic side-effects from over-expression of the therapeutic gene, and adverse events caused by immune system reactions to the viral delivery systems currently used to deliver the therapeutic genes," said Pedro Lowenstein, M.D., Ph.D., co-director of the Institute and co-author of the study. "Now, we’ve engineered a genetic switch in a novel gene transfer vector that will overcome those barriers and set the stage to allow the next phase of research to occur."

Gene therapy is an experimental treatment that uses genetically engineered viruses (vectors) to transfer therapeutic genes and/or proteins into cells. As in a viral infection, the viruses work by tricking cells into accepting them as part of their own genetic machinery. To make them safe, scientists remove the viral genes that cause infection and engineer them so that they stop reproducing after they have delivered the therapeutic gene.

In this study, researchers created a genetic switch system that is turned on in the presence of the antibiotic tetracycline. Therefore, if this method is tested eventually in humans, patients would need to be given this antibiotic before they begin gene therapy treatment. The switch system also produces a protein called silencer, which completely shuts down gene expression in the "off" state, thereby preventing leakage of the therapeutic gene when it is no longer needed. According to Castro, this novel vector system is much less likely to create an undesirable immune response in the host and would still be functional in the presence of an infection to wild type adenovirus (a non-engineered virus that causes conjunctivitis and upper respiratory tract infections) as is present in a high percentage of patients undergoing clinical trails. These are the main hurdles that needed to be overcome before gene therapy can be considered a safe and efficacious clinical strategy.

According to Drs. Castro and Lowenstein, the next step in the development of this new signaling system is to activate the newly developed genetic switch to actively express compounds that are known to be effective at reversing the symptoms and rescuing the damaged neurons in Parkinson’s disease patients. Researchers hope to begin a Phase 1 clinical trial in humans in the near future.

Simi Singer | EurekAlert!
Further information:
http://www.cshs.org
http://www.cshs.org/gtri/

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

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

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>