The unsung hero of chemical reactions: How was DNAzyme discovered in the laboratory?

In the world of biochemistry, the role of enzymes is self-evident. However, when it comes to DNA enzymes, or deoxyribonucleases, the exploration of this field seems relatively mysterious. Deoxyribozymes not only catalyze specific chemical reactions, but their potential and existence also fill the scientific community with curiosity and challenges. Research in this area continues to reveal the diversity of DNA enzymes, their potential applications in the laboratory, and most importantly, how they were discovered.

Deoxyribozymes are DNA oligonucleotides that can perform specific chemical reactions, but there are only a handful of them in nature.

The concept of deoxyribozyme was first proposed by scientists in 1994, when master's student Ronald Breaker discovered the first deoxyribozyme, GR-5, while conducting research at the Scripps Research Institute. His discovery is similar to the action of biological enzymes, which can rapidly catalyze certain reactions, particularly when they are dependent on metal ions.

Compared with traditional protein enzymes, the catalytic capacity of deoxyribozymes is relatively limited. This is because DNA is composed of only four chemically similar nucleotides, which do not have an adequate number of functional groups. The structural differences of dioxyribose, especially the lack of a 2'-hydroxyl group, further limit the catalytic ability of deoxyribozymes. However, researchers are finding that even though these enzymes are rarely seen in nature, their potential for creation in the laboratory is exciting.

The discovery of DNAzymes led to high-throughput in vitro selection techniques, which allow researchers to screen DNA sequences for specific catalytic functions.

During the in vitro selection process, researchers create a large library of random DNA sequences containing thousands of unique DNA strands, each specifically designed to facilitate subsequent screening. Through this method, scientists were able to find deoxyribozymes with catalytic capabilities through dozens of screening and amplification processes, thereby dramatically improving the efficiency of the catalytic reaction.

In addition to the continuous improvement of screening methods, further in vitro evolution techniques have also enabled scientists to evolve new deoxyribozymes from non-catalytic precursor sequences. In this process, gene recombination and mutation promote the production of new enzymes, making these new DNAzymes more active in catalyzing specific reactions.

These findings not only increase our understanding of DNAzymes, but also pave the way for future biomedical applications.

Today, DNAzymes are used in a wide range of applications. From antiviral drugs to new disease treatment strategies, researchers are working hard to explore its potential applications in various aspects. Taking recent clinical studies on asthma and eczema as an example, DNA enzymes targeting the key transcription factor GATA3 can significantly inhibit allergic reactions, providing patients with a new treatment option.

The rapid evolution of DNA enzymes and their applications in synthetic chemistry demonstrate the unique potential of DNA as a catalyst. At the same time, this has also given rise to enthusiasm and expectations for further exploration in this field.

Deoxyribozymes have also shown their value in the development of metal biosensors, which provides a new path for environmental detection. In these application cases, scientists use DNAzymes to monitor the presence of pollutants and strengthen supervision of environmental protection.

As research progresses, the multiple functions of DNAzymes become increasingly apparent. However, despite the many breakthroughs, this field still requires more exploration and experimentation to unlock its full potential. After all, as technology advances, what role will DNAzymes play in future science?

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