Delivery system for gene therapy may help treat arthritis

May 15, 2012
Drs. Andrew L. Mellor and Lei Huang at Georgia Health Sciences University have shown a system called DNA nanoparticles, used to deliver genes or drugs directly into cells to treat a variety of diseases, may help arthritis without delivering anything. Credit: Phil Jones, GHSU Photographer

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 of , 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 .

"It's like pouring water on a fire," said Dr. Andrew L. Mellor, Director of the GHSU's Medical College of Georgia 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, and Parkinson's disease. The new findings suggest the DNA nanoparticle technique has value as well for such as arthritis, 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 called phagocytes, white blood that gobble up undesirables like bacteria and dying cells, start making more IDO in response to the DNA nanoparticle's arrival. " 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.

Explore further: Newest cancer therapies multi-task to eliminate tumors

Related Stories

Newest cancer therapies multi-task to eliminate tumors

September 16, 2011
Some of the newest therapies in the war on cancer remove the brakes cancer puts on the immune system, Georgia Health Sciences University researchers report.

Natural method for clearing cellular debris provides new targets for lupus treatment

February 24, 2012
Cells that die naturally generate a lot of internal debris that can trigger the immune system to attack the body, leading to diseases such as lupus.

Recommended for you

Immune system can be modulated by targeted manipulation of cell metabolism

August 21, 2017
In its attempt to fight a serious bacterial infection, caused by listeria, for example, the immune system can become so over-activated that the resulting inflammatory response and its consequences can quickly lead to death. ...

Australian researchers in peanut allergy breakthrough

August 17, 2017
Australian researchers have reported a major breakthrough in the relief of deadly peanut allergy with the discovery of a long-lasting treatment they say offers hope that a cure will soon be possible.

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Study identifies a new way to prevent a deadly fungal infection spreading to the brain

August 16, 2017
Research led by the University of Birmingham has discovered a way to stop a deadly fungus from 'hijacking' the body's immune system and spreading to the brain.

Biophysics explains how immune cells kill bacteria

August 16, 2017
(Tokyo, August 16) A new data analysis technique, moving subtrajectory analysis, designed by researchers at Tokyo Institute of Technology, defines the dynamics and kinetics of key molecules in the immune response to an infection. ...

How a nutrient, glutamine, can control gene programs in cells

August 15, 2017
The 200 different types of cells in the body all start with the same DNA genome. To differentiate into families of bone cells, muscle cells, blood cells, neurons and the rest, differing gene programs have to be turned on ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.