LA JOLLA, CA- DNA, already quite a busy molecule, can also be employed in the business of breaking apart molecules, report researchers from the Scripps Research Institute.

Researchers have known for more than ten years that RNA could act like an enzyme and cleave other RNA molecules. The Scripps researchers reasoned that since DNA contains most of the same functional groups as RNA, it too might have catalytic activity. Using technique called in vitro evolution, they tested one hundred million million random sequences of single stranded DNA for their ability to cleave a target ribonucleoside embedded within otherwise normal DNA sequences.

Five successive rounds of selective amplification produced what they were looking for, a DNA catalyst. The catalytic sequence was then isolated and several variants were cloned. The researchers then constructed a simplified version of the both the catalytic and substrate domains based on common features of the variants. The resulting DNA enzyme has a catalytic rate comparable to that seen with RNA enzymes.

"DNA now joins RNA and protein on the list of biological macromolecules that can exhibit enzymatic activity. The extent of DNA's catalytic abilities remains to be explored, but these explorations will be facilitated by in vitro selection methods such as those employed in this study," the researchers report.

What's more the DNA enzymes appear to offer a number of advantages over other macromolecular catalysts. For one thing, the ready availability of automated DNA synthesizing equipment makes the enzymes relatively simple to prepare. Also, the DNA enzymes are very stable compared with RNA, which facilitates their use in biophysical studies. Considering these factors, other synthetic DNA enzymes, now dubbed 'deoxyribozymes' should appear in the near future.

The development of DNA enzymes parallels earlier work in the development of RNA enzymes (ribozymes). The initial discovery that RNA could act like an enzyme caused a significant shift in molecular biology. The concept that RNA might reproduce itself without the intervention of proteins provided new ways of looking at the origins of life. Also, the observation that ribozymes could be designed to target other RNA molecules provided researchers with a new approach to creating antiviral therapies.

Early attempts to use RNA enzymes therapeutically have been limited by the quick degradation of the molecules once they are injected. The fact that DNA is a million times more stable than RNA suggests it may be more suitable for therapeutic applications, the researchers say.

For a detailed description of the laboratory methods used to produce the first DNA enzyme, see- Beaker et al., Chemistry and Biology, v.1, n.4, 12/94.

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