The University of Minnesota won a patent on a new method of treatment for coronary disease using recent advances in synthetic DNA to address an underlying cause of chronic heart failure.

Heart failure is one of the leading causes of sudden death in developed countries, but most current therapies are merely aimed at mitigating its symptoms. However, in a patent granted to the U of M in August, a team of researchers revealed a novel method using artificial DNA “aptamers” to target the subcellular mechanisms that contribute to heart failure.

Its chief inventors are Michael Bowser of the U of M chemistry department; Gianluigi Veglia of its College of Biological Sciences; and Joseph Metzger, chairman of the U’s integrated biology and physiology departments. Also credited as inventors are U of M research associates Meng Jing, Raffaelo Verardi and Brian Thompson.

The newly patented technology, if it is ultimately proven in clinical trials and commercialized, could have the potential to become an early entrant into the emerging field of translating advances in synthetic DNA into actual medical applications.

One kind of manmade DNA is referred to as “xeno nucleic acid,” or XNA, which is formed into “aptamers”—short strands of genetic material manufactured in the lab for their unique ability to selectively target certain molecules in the body and bind with them. XNA aptamers combine this powerful targeting ability with an ease of manufacture and high chemical stability—something natural DNA cannot match. 

That’s why these aptamers have generated tremendous levels of interest for both therapeutic and diagnostic applications in medical science. For instance, they can be used as efficient delivery agents for conventional drugs as well for toxic genetic payloads which can be used to selectively kill cancer cells while leaving others intact. 

XNA aptamers are being seen, for example, as potential alternatives for antibodies against viral infections. They can be directed against any protein in infected cells, or against any components of viruses such as hepatitis. They are also being touted as a new opening in the fight against blood cancers, where they are being tested in their first clinical trials.

Also seen as a prime candidate for treatment with synthetic DNA is heart failure (HF).

One of the underlying causes of HF is reduced levels of a protein called sarco/endoplasmic reticulum Ca2+ATPase (SERCA2a), which acts as “calcium pump” across the membrane of the heart when it relaxes between contractions. It acts in concert with another protein called phospholamban (PLN) to regulate heart relaxation and remove calcium.
When SERCA2a is deficient, it causes the heart to have trouble contracting. Animal studies have shown that restoring SERCA2a levels via gene therapy corrects the contracting abnormalities and improves energy.

The newly patented U of M technology is aimed at that dynamic. It cites U of M research performed by Bowser in which he has worked on new techniques to improve the effectiveness of synthetic DNA on targeting membrane proteins such as those in the heart.

Specifically, the patent is for a unique method of using XNA aptamers to effectively bind with PLN, thus inducing longer heart relaxation time and counteracting the deficiency of SERCA2a.