Innovative DNA Technology May Provide More Efficient Disease Detection and Treatment

Researchers have developed a novel DNA aptamer with potential to improve detection and targeted treatment of infectious diseases and other illnesses, such as cancer.

The new aptamer was developed by researchers at the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR (Agency for Science, Technology and Research; Singapore) by improving on existing technologies for synthesizing aptamers, modified single-stranded DNA molecules. DNA aptamers can specifically bind to molecular targets in the body such as proteins, viruses, bacteria, and cells. DNA aptamers are made for a given target to bind and inhibit its activity, giving this technology potential for disease detection and drug delivery. But no DNA aptamers have been approved for clinical use because current aptamers do not bind well to targets and are easily digested by enzymes.

“To overcome these challenges, we have created a DNA aptamer with strong binding ability and stability with superior efficacy. We hope to use our DNA aptamers as the platform technology for diagnostics and new drug development,” said IBN Executive Director Prof. Jackie Y. Ying.

The research team was led by principal research scientist and team leader Dr. Ichiro Hirao. To tackle the weak target-binding problem, they added a new artificial component, an “unnatural base,” to a standard DNA aptamer, which typically has 4 components. The addition of the 5th component greatly enhanced the binding ability to the molecular target by 100 times compared to conventional DNA aptamers. Furthermore, to prevent the aptamer from being quickly digested by enzymes, a unique “mini-hairpin DNA” was added.

Dr. Hirao explained: “The mini-hairpin DNAs have an unusually stable and compact stem-loop structure, like a hairpin, of small DNA fragments. Their structure strongly resists the digestive enzymes, so I added them to specific positions on the DNA aptamer to act as a protective shield. Usually DNAs are digested within one hour in blood at body temperature. With the mini-hairpin DNA, our DNA aptamers can survive for days instead of hours. This is important for pharmaceutical applications, which require the therapeutic to remain in the body for a longer period.”

DNA aptamers could replace or complement the existing use of antibodies in drugs for targeted disease treatment. Antibodies often cause undesirable immune response and are not easy to mass produce with high quality.

“We can now generate very promising DNA aptamers for clinical use. Our aptamers are more efficient, and lower in cost and toxicity compared to conventional methods. The next step of our research is to use the aptamers to detect and deactivate target molecules and cells that cause infectious diseases, such as dengue, malaria, and Methicillin-resistant Staphylococcus aureus (MRSA), as well as cancer,” added Dr Hirao.

The study, by Matsunaga K et al, was published December 22, 2015, in the journal Scientific Reports.

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Institute of Bioengineering and Nanotechnology at A*STAR