Breakthrough DNA Ointment Could Revolutionize Contact Allergy Treatment

Researchers at the University of Bonn have isolated a DNA molecule that, in mice, shows promise in combating contact allergies. The so-called aptamer binds to specific immune system signaling molecules, effectively neutralizing them. Remarkably, this works even when the active compound is applied to the skin as an ointment. The teams involved hope that such aptamer-based creams could one day be used to treat other skin conditions as well. Their findings have now been published in the journal Molecular Therapy – Nucleic Acids.

DNA is a long molecule composed of different building blocks linked in sequence, much like letters in a sentence. Just as a sentence encodes information, DNA strands can do the same. At the same time, DNA is inherently "sticky," almost like a microscopic Velcro strip. In chromosomes, it exists as two parallel strands whose adhesive surfaces face each other.

Aptamers, by contrast, are single-stranded. This allows them to bind to other molecules and influence their function. Which molecules they attach to depends on the sequence of their building blocks: different aptamers bind to different targets with high specificity. It is precisely this property that makes them so valuable in drug research.

Fishing in the Aptamer Library

"Today, it is relatively straightforward to generate vast libraries of aptamers with randomly varied sequences," explains Professor Günter Mayer of the LIMES Institute (an acronym for Life and Medical Sciences) at the University of Bonn. "Some of these libraries contain millions of times more potential drug candidates than there are people on Earth."

To block a specific target with aptamers, researchers simply use them as bait: when dipped into the mix, only the aptamers that fit the target will stick. "Using this method, we isolated aptamers that bind to a specific immune protein called CCL22," says Mayer, who is also a member of the University of Bonn's Transdisciplinary Research Areas Matter and Life & Health. "We then chemically modified these hits and further optimized them."

The Immune System's Lure

CCL22 is a chemokine—a type of signaling molecule that directs cell movement in the body. When certain immune cells detect components of bacteria or viruses, for example, they release chemokines to summon the body's defenses.

A similar process occurs in contact allergies: the body's own proteins are altered by an allergen, such as a nickel-containing necklace. Though these changes are harmless, the immune system perceives them as foreign, triggering the release of CCL22, among other responses. CCL22 then attracts T cells to the site, leading to an allergic reaction.

Aptamer Ointment Relieves Allergies in Mice

"We administered an aptamer targeting CCL22 to mice," explains Mayer's colleague Professor Irmgard Förster, who studies immunology and the environment at the LIMES Institute and is also a member of the Cluster of Excellence ImmunoSensation2 and the Transdisciplinary Research Area Life and Health. "This effectively blocked the chemokine. Metaphorically speaking, the T cells' 'noses' could no longer detect the lure because it was masked by the aptamer."

As a result, the allergic skin reaction subsided after treatment with the aptamer. Surprisingly, this also worked when the compound was applied as an ointment to inflamed areas. "For the first time, we've shown that aptamers can be administered in this form," Mayer emphasizes. "The two lead authors, Anna Jonczyk and Marlene Gottschalk, who conducted the experiments, were themselves surprised and excited by this result and its future therapeutic potential."

Unclear Whether the Approach Will Work in Humans

The researchers now plan to investigate whether this method could also treat other skin diseases. "It's possible that conditions like atopic dermatitis or even malignant melanomas could be treated with specialized aptamer creams targeting this or other proteins," Förster hopes. "However, our findings are currently limited to mice. Whether this approach will prove effective in humans remains to be seen."