DNA carries the genetic information of all living organisms and consists of only four different building blocks, nucleotides. Nucleotides are made up of three distinctive parts: a sugar molecule, a phosphate group, and one of the four nucleobases adenine, thymine, guanine, and cytosine. The nucleotides line up millions of times and form the double helix of DNA, similar to a spiral staircase. Scientists from the UoC Department of Chemistry have now shown that the structure of nucleotides can be greatly modified in the laboratory.
The researchers developed the so-called threofuranosyl nucleic acid (TNA) with a new additional base pair. These are the first steps on the path towards fully artificial nucleic acids with improved chemical functionalities. The study ‘Expanding the space horizon of xenonucleic acids: three nucleic acids with greater information storage’ was published in the journal Journal of the American Chemical Society.
Artificial nucleic acids differ in structure from their originals. These changes affect its stability and function. “Our threofuranosyl nucleic acid is more stable than the natural nucleic acids DNA and RNA, which brings many advantages for future therapeutic use,” said Professor Dr. Stephanie Kath-Schorr. For the study, the 5-carbon sugar deoxyribose, which forms the backbone of DNA, was replaced with a 4-carbon sugar. Additionally, the number of nucleobases was increased from four to six. When exchanging sugar, TNA is not recognized by the cell’s own degradation enzymes. This has been a problem with nucleic acid-based therapies, as synthetically produced RNA introduced into a cell quickly degrades and loses its effect. Introducing TNA into cells that go unnoticed could now maintain the effect for longer.
“In addition, the built-in unnatural base pair allows for alternative binding options for targeting molecules in the cell,” added Hannah Depmeier, lead author of the study. Kath-Schorr is sure that such a function can be used especially in the development of new aptamers, short DNA or RNA sequences, which can be used for the specific control of cellular mechanisms. TNAs could also be used for the targeted transport of drugs to specific organs in the body (targeted drug delivery), as well as for diagnosis; They could also be useful for the recognition of viral proteins or biomarkers.