Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Steroid-Coated DNA Represents New Approach to Gene DeliverySteroid-Coated DNA Represents New Approach to Gene Delivery

12.02.2004


Coating DNA with a topical steroid might make for more effective therapeutic gene delivery, according to bioengineers at the University of Pennsylvania. The researchers have shown that a common anti-inflammatory steroid, wrapped around a strand of DNA, can prevent the immune responses commonly associated with gene-transfer techniques.



Studies of the technique, performed in animal models, are presented in the Feb. 15 issue of the journal Gene Therapy, available online now.

"The steroid coating not only allows the gene to be taken up into a cell more easily, but the steroid itself also prevents the sort of inflammatory immune response seen in gene transfer therapy," said Scott Diamond, senior author and professor of bioengineering at Penn and associate director of Penn Institute for Medicine and Engineering. "The concept paves the way to coupling therapeutic gene delivery with a pharamacological agent, an approach that mitigates some of the drawbacks to the gene-delivery techniques in use now."


Currently there are two basic approaches to delivering therapeutic genes: nonviral and viral. Injecting a subject with pure DNA is possible, but a DNA molecule, by itself, has inherent trouble in entering cells. Viral carriers can serve as delivery vehicles for DNA, literally infecting cells with new genes. Both methods, however, are associated with the creation of inflammatory immune responses that reduces the action of the therapeutic gene.

DNA is a large and negatively charged molecule, which is the source of the stumbling point in getting cells to take up DNA. To counter the negative charge of DNA, Diamond and his colleagues took a common steroid, dexamethasone, and made it tickyby adding a nitrogen-rich, postively charged tail. This tail provides the glue that attaches the steroid to the naked DNA.

"The steroid is a fatty lipid so, in essense, we have greased up DNA for cellular uptake," Diamond said, "Plus the cells get a big dose of steroid."

According to Diamond, the chemistry involved in manufacturing this new steroid vehicle is a fairly straightforward, one-step process that is simple compared to creating viral gene therapy vectors.

"But this is more than just ene therapy on steroids," Diamond said. "The dexmethasone not only eased inflammation in an animal model, but, as our study showed, actually allowed the cells to use the foreign DNA more effectively."

In addition, corticosteroids can suppress the major inflammatory cytokines created by the immune response after gene delivery. According to studies in cell culture and animal models, the steroid-coated DNA showed lower initial inflammation and greater expression of the gene over time. The results have encouraged the researchers to continue studies and to envision broader application of the technique toward diseases that might also benefit from gene-transfer therapy.

"In humans, especially in inflamatory diseases, a steroid coating would greatly enhance the chances of successful gene transfer," Diamond said. "As an alternative, I could foresee the use of this coating technique to tailor therapies by choosing drugs that would amplify the benefit of a particular therapeutic gene."

Funding for this research was supported by grants from the National Institutes of Health and the Cystic Fibrosis Foundation.

Greg Lester | University of Pennsylvania
Further information:
http://www.upenn.edu/pennnews/article.php?id=586

More articles from Life Sciences:

nachricht Show me your leaves - Health check for urban trees
12.12.2017 | Gesellschaft für Ökologie e.V.

nachricht Liver Cancer: Lipid Synthesis Promotes Tumor Formation
12.12.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Long-lived storage of a photonic qubit for worldwide teleportation

12.12.2017 | Physics and Astronomy

Multi-year submarine-canyon study challenges textbook theories about turbidity currents

12.12.2017 | Earth Sciences

Electromagnetic water cloak eliminates drag and wake

12.12.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>