A research team at the University of California, Irvine has developed a new enzyme called 10-92 that is capable of producing a synthetic genetic material known as threose nucleic acid (TNA). This advancement in enzyme technology brings the scientific community closer to being able to synthesize artificial chains of TNA, which is more stable than DNA. The potential applications of this breakthrough include the development of more powerful and precise therapeutic options for treating a variety of diseases such as cancer, autoimmune disorders, metabolic conditions, and infectious diseases.
The research team’s work was recently published in the journal Nature Catalysis, detailing how they were able to design the 10-92 enzyme to achieve faithful and rapid TNA synthesis. By overcoming challenges faced in previous enzyme design strategies, the team has made significant progress toward attaining the ability to synthesize TNA drugs that could revolutionize the field of medicine. DNA polymerases, enzymes responsible for replicating organisms’ genomes accurately and efficiently, play crucial roles in biotechnology and healthcare, as evidenced by their importance in the fight against COVID-19.
Corresponding author John Chaput, a professor of pharmaceutical sciences at UC Irvine, emphasized the significance of the team’s accomplishment, calling it a major milestone in the evolution of synthetic biology. He highlighted the exciting potential for new therapeutic applications that could be made possible by narrowing the performance gap between natural and artificial enzyme systems. Unlike DNA, TNA’s enhanced stability makes it suitable for a wider range of treatments, and the development of the 10-92 TNA polymerase will help expand the use of TNA in various medical treatments.
The 10-92 TNA polymerase was engineered using a technique called homologous recombination, which involves rearranging polymerase fragments from related species of archaebacteria. Through multiple cycles of evolution, the researchers were able to identify polymerase variants with increasing activity, ultimately leading to the development of a variant that closely mimics natural enzymes. This new enzyme has the potential to revolutionize drug development, as TNA’s resistance to enzymatic and chemical degradation makes it an ideal candidate for creating therapeutic aptamers that can bind to target molecules with high specificity.
According to Chaput, the drugs of the future could look very different from those currently in use, as TNA’s durability and other unique characteristics open up new possibilities for treatment options. By engineering enzymes like the 10-92 TNA polymerase, researchers can explore novel approaches to drug development that may overcome the limitations of traditional treatments, such as antibodies. The team at UC Irvine believes that these advancements could have a significant positive impact on human health, leading to the discovery of groundbreaking new therapies that improve patient outcomes and quality of life.
