Artificial building block of life, called TNA, created in the lab

The blueprint of life, DNA, is an intricate molecular structure that encodes the genetic instructions for all living organisms. It is composed of only four nucleotides, each consisting of a sugar molecule, a phosphate group, and one of four nucleobases: adenine, thymine, guanine, and cytosine.

These nucleotides are arranged into the iconic DNA double helix, reminiscent of a spiral staircase, stretching millions of units long.

Breaking new ground with TNA

A remarkable study by the University of Chicago’s Department of Chemistry, scientists have pushed the boundaries of genetic engineering by demonstrating the ability to extensively modify nucleotide structures in the lab.

The research introduces an innovative variant of nucleic acid, termed threofuranosyl nucleic acid (TNA), which incorporates a novel base pair, marking a significant leap towards the development of entirely artificial nucleic acids endowed with superior chemical functionalities.

This pioneering work, titled ‘Expanding the Horizon of the Xeno Nucleic Acid Space: Threose Nucleic Acids with Increased Information Storage’, has been featured in the Journal of the American Chemical Society.

Enhancements and advantages of TNA

Artificial nucleic acids like TNA diverge in structure from their natural counterparts, DNA and RNA. These modifications not only enhance their stability but also alter their functionality.

“Our threofuranosyl nucleic acid is more stable than the naturally occurring nucleic acids DNA and RNA, which brings many advantages for future therapeutic use,” elucidates Professor Dr. Stephanie Kath-Schorr.

In crafting TNA, the conventional 5-carbon sugar backbone found in DNA, deoxyribose, was substituted with a 4-carbon sugar variant. Moreover, the diversity of nucleobases expanded from the standard four to six.

Broadening therapeutic horizons

This structural innovation ensures that TNA evades recognition and subsequent degradation by the cell’s enzymes, a notable challenge in the realm of nucleic acid-based therapeutics.

Synthetic RNA, when introduced into cells, is rapidly broken down, diminishing its efficacy. TNAs, however, persist undetected, prolonging their therapeutic impact.

“In addition, the built-in unnatural base pair enables alternative binding options to target molecules in the cell,” highlights Hannah Depmeier, lead author of the study.

This feature opens new avenues for precisely controlling cellular mechanisms through the development of novel aptamers — short DNA or RNA sequences.

Kath-Schorr is optimistic about the potential applications of TNAs, ranging from the targeted delivery of drugs to specific organs, to diagnostic uses such as the detection of viral proteins or biomarkers.

The promise of TNA in genetic medicine

In summary, scientists at the University of Chicago have made a breakthrough, creating a synthetic nucleic acid, threofuranosyl nucleic acid (TNA), in the lab.

By introducing a more stable and versatile synthetic form of nucleic acid, this innovation paves the way for advanced therapeutic applications, targeted drug delivery, and precise diagnostics.

As we embrace the possibilities offered by TNAs, from enhancing the effectiveness of treatments to revolutionizing the way we approach diseases, the future of medicine and genetic research stands on the cusp of transformation.

The journey into this uncharted genetic frontier promises not only to deepen our understanding of life’s molecular foundations but also to unlock unprecedented opportunities for improving human health worldwide.

The full study was published in the journal Journal of the American Chemical Society.

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