Researchers at Yale have succeeded in making RNA biochips, which in the future may be engineered to detect a wide range of compounds important in medicine, industry and even for biological and chemical warfare defense.
"We should be able to produce robust biochips that can withstand extreme conditions that would destroy other biological materials," says Ronald Breaker, associate professor of molecular, cellular and developmental biology and lead author of the study published in the current issue of Nature Biotechnology.
Scientists in the last several years have built DNA biochips, which are small chip-like surfaces with pixels of DNA arrayed on the surface. These DNA molecules can be used to detect DNA gene sequences from complex biological mixtures.
Breaker says a typical DNA chip functions by exploiting the interactions that were revealed by Watson and Crick in 1953, that complementary strands of DNA form a double helix. As a result, standard DNA chips are engineered to see specific DNA or RNA sequences and nothing else.
"In contrast, advanced versions of our prototype RNA biochip can be used to see many different targets like drugs, toxins and metabolites, as well as both proteins and nucleic acids," he says. "We even have a molecular switch that can be triggered indirectly by UV light. In other words, our RNAs fold into intricate 3-D structures that selectively recognize a wide range of targets, a function that is similar to antibodies. Therefore, advanced RNA biochips should be able to be used to detect almost anything that an RNA can be made to bind."
Last year at Yale, Peter Moore, the Eugene Higgins Professor of Chemistry, and Thomas Steitz, the Eugene Higgins Professor of Molecular Biophysics and Biochemistry and investigator for the Howard Hughes Medical Institute, determined that a ribosome is a ribozyme. Their finding, Breaker says, indicates that the ribosome is a holdover from the transition between an RNA world and the protein DNA world that we have today.
"We speculated that early in the evolution of life, living systems would have wanted to use molecular switches made out of RNA," Breaker says. "This is based on the theory that life either began with, or passed through a time at which, all necessary metabolism was run by RNA. There were no protein enzymes. There was no DNA. All of the shots were called by RNA. One then can infer, if the more aggressive theories are correct, that RNA organisms four billion years ago would have had a need to make use of RNA molecular switches to control metabolism."
He says his laboratory's work gives evidence in support of the RNA world theory because it shows that nucleic acids can be very sophisticated at doing chemistry and at controlling chemistry. And it provides scientists with new molecular tools for application in therapeutics and in biotechnology.
Breaker's lab pioneered the "test tube evolution" of the RNA molecular switches and initiated the RNA biochip system a year ago.
The advantage of any array of biosensors is the massive parallel analysis of complex test solutions, he says. Putting all of the biosensors on milli- or micro-scale platforms gives the added advantage of miniaturization, which saves on space and on the resources needed to use them.
"The goal of our RNA biochip research is to put the capability of a thousand scientists into a dime-sized chip while generating the answers you want a thousand times faster," Breaker says.
-- By Jacqueline Weaver
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