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FEATURE ARTICLE

Survival of the Fittest Molecule

Biochemists harness a novel form of evolution to sculpt new compounds for the fight against dengue fever, cancer and other modern plagues

Willem Stemmer, Brett Holland

Figure 6. DNA family breedingClick to Enlarge Image

The increasing sophistication of molecular biology and the advent of the –omics sciences (genomics, proteomics, metabolomics) have inaugurated an age in which almost any gene product can be used as a potential therapeutic. Unfortunately, many native cellular proteins are ill-adapted for commercial use—they're unstable at a different pH, or they need greater specificity, or their activity is diminished—creating a roadblock to their actual use as drugs. To get around this roadblock, biochemists have often used a form of simulated evolution to modify existing compounds into new and more useful forms. This has traditionally been done with a "brute force" approach, in which genes and gene products are randomly altered and tested for improved efficacy or specificity. Unfortunately, such strategies are extremely labor- and time-intensive. In "Survival of the Fittest Molecule," the authors discuss a more efficient approach: A form of directed evolution called "DNA breeding," which shuffles bits of DNA that have already been sculpted by countless generations of natural selection. This strategy has dramatically decreased the time and effort required to develop new drug candidates, and it has already produced a range of new molecules, including immune system enhancers and a dengue fever vaccine.


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