Triple Helix: Designing a New Molecule of Life

For all the magnificent diversity of life on this planet, ranging from tiny bacteria to majestic blue whales, from sunshine-harv­­est­­ing plants to mineral-digesting endoliths miles underground, only one kind of “life as we know it” exists. All these organisms are based on nucleic acids—DNA and RNA—and proteins, working together more or less as described by the so-called central dogma of molecular biology: DNA stores information that is transcribed into RNA, which then serves as a template for producing a protein. The proteins, in turn, serve as important structural elements in tissues and, as enzymes, are the cell’s workhorses.

Yet scientists dream of synthesizing life that is utterly alien to this world—both to better understand the minimum components required for life (as part of the quest to uncover the essence of life and how life originated on earth) and, frankly, to see if they can do it. That is, they hope to put together a novel combination of molecules that can self-organize, metabolize (make use of an energy source), grow, reproduce and evolve.

A molecule that some researchers study in pursuit of this vision is peptide nucleic acid (PNA), which mimics the information-storing features of DNA and RNA but is built on a proteinlike backbone that is simpler and sturdier than their sugar-phosphate backbones. My group developed PNA more than 15 years ago in the course of a project with a rather more immediately useful goal than the creation of unprecedented life-forms. We sought to design drugs that would work by acting on the DNA composing specific genes, to either block or enhance the gene’s expression (the production of the protein it encodes). Such drugs would be conceptually similar to “antisense” compounds, such as short DNA or RNA strands that bind to a specific RNA sequence to interfere with the production of disease-related proteins [see “Hitting the Genetic Off Switch,” by Gary Stix; Scientific American, October 2004].

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