Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Delivery system for gene therapy may help treat arthritis

15.05.2012
A DNA-covered submicroscopic bead used to deliver genes or drugs directly into cells to treat disease appears to have therapeutic value just by showing up, researchers report.

Within a few hours of injecting empty-handed DNA nanoparticles, Georgia Health Sciences University researchers were surprised to see increased expression of an enzyme that calms the immune response.

In an animal model of rheumatoid arthritis, the enhanced expression of indoleomine 2,3 dioxygenase, or IDO, significantly reduced the hallmark limb joint swelling and inflammation of this debilitating autoimmune disease, researchers report in the study featured on the cover of The Journal of Immunology.

"It's like pouring water on a fire," said Dr. Andrew L. Mellor, Director of the GHSU's Medical College of Georgia Immunotherapy Center and the study's corresponding author. "The fire is burning down the house, which in this case is the tissue normally required for your joints to work smoothly," Mellor said of the immune system's inexplicable attack on bone-cushioning cartilage. "When IDO levels are high, there is more water to control the fire."

Several delivery systems are used for gene therapy, which is used to treat conditions including cancer, HIV infection and Parkinson's disease. The new findings suggest the DNA nanoparticle technique has value as well for autoimmune diseases such as arthritis, type 1 diabetes and lupus. "We want to induce IDO because it protects healthy tissue from destruction by the immune system," Mellor said.

The researchers were exploring IDO's autoimmune treatment potential by inserting the human IDO gene into DNA nanoparticles. They hoped to enhance IDO expression in their arthritis model when Dr. Lei Huang, Assistant Research Scientist and the paper's first author, serendipitously found that the DNA nanoparticle itself produced the desired result. Exactly how and why is still being pursued. Early evidence suggests that immune cells called phagocytes, white blood cells that gobble up undesirables like bacteria and dying cells, start making more IDO in response to the DNA nanoparticle's arrival. "Phagocytes eat it and respond quickly to it and the effect we measure is IDO," Mellor said.

Dr. Tracy L. McGaha, GHSU immunologist and a co-author on the current study, recently discovered that similar cells also prevented development of systemic lupus erythematosus in mice.

Follow-up studies include documenting all cells that respond by producing more IDO. GHSU researchers already are working with biopolymer experts at the Massachusetts Institute of Technology, the University of California, Berkeley and the Georgia Institute of Technology to identify the optimal polymer.

The polymer used in the study is not biodegradable so the researchers need one that will eventually safely degrade in the body. Ideally, they'd also like it to target specific cells, such as those near inflamed joints, to minimize any potential ill effects.

"It's like a bead and you wrap the DNA around it," Mellor said of the polymer. While the DNA does not have to carry anything to get the desired response in this case, DNA itself is essential to make cells express IDO. To ensure that IDO expression was responsible for the improvements, they also performed experiments in mice given an IDO inhibitor in their drinking water and in mice genetically altered to not express IDO. "Without access to the IDO pathway, the therapy no longer works," Mellor said.

Drs. Andrew Mellor and David Munn reported in 1998 in the journal Science that the fetus expresses IDO to help avoid rejection by the mother's immune system. Subsequent studies have shown tumors also use IDO for protection and clinical trials are studying the tumor-fighting potential of an IDO inhibitor. On the flip side, there is evidence that increasing IDO expression can protect transplanted organs and counter autoimmune disease.

Mellor is the Bradley-Turner and Georgia Research Alliance Eminent Scholar in Molecular Immunogenetics at MCG. The research was funded by the Carlos and Marguerite Mason Trust and the National Institutes of Health and a patent is pending on the findings.

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

More articles from Health and Medicine:

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

nachricht The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine

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: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>